Academia.eduAcademia.edu

Biochemical Pathways.[1999 EN].G Michal OCR

Profile image of andrey khorstandrey khorst

Abstract
sparkles

AI

The book "Biochemical Pathways" aims to provide concise and comprehensive information on metabolic pathways, enzymatic reactions, and their regulation, without the extensive historical context typically found in textbooks. It focuses on a variety of biological systems, including bacteria, plants, and animals, presenting knowledge through clear illustrations and tables to facilitate quick understanding. The work is designed for readers looking for a systematic overview of biochemical interrelationships while omitting detailed experimental methods and the complete range of literature references.

Figures (446)
Although the bond angles of a furanose ring would permit an almost planar suucture the interference ot substituents with each other causes a slight bend ing (puckcung) eg to a halt chair (= envelope) structure in nucicotides and nucleic acids (Fig 1 2 3)
Although the bond angles of a furanose ring would permit an almost planar suucture the interference ot substituents with each other causes a slight bend ing (puckcung) eg to a halt chair (= envelope) structure in nucicotides and nucleic acids (Fig 1 2 3)
Figure 1 2-4 Examples of Glycosidic Bonds The metabolism of di and oligosaccharides also involves many isomcriza uuons (e g between aldoses and ketoses) and epimerizauions The conversions into deoxy sugars (rhamnose fucose) are multistep reactions
Figure 1 2-4 Examples of Glycosidic Bonds The metabolism of di and oligosaccharides also involves many isomcriza uuons (e g between aldoses and ketoses) and epimerizauions The conversions into deoxy sugars (rhamnose fucose) are multistep reactions
The linear form of carbohydrates usually shown as Fischer projection (igands drawn horizontally are in tront of the plane ligands drawn vertically are behind the plane eg iw Fig !2 1) The ring form 1s either diawn as Ha_ worth formula (Fig 12 2 disregarding the bent ring structure) or as boat/chair tormula (Fig 1 2 3)
The linear form of carbohydrates usually shown as Fischer projection (igands drawn horizontally are in tront of the plane ligands drawn vertically are behind the plane eg iw Fig !2 1) The ring form 1s either diawn as Ha_ worth formula (Fig 12 2 disregarding the bent ring structure) or as boat/chair tormula (Fig 1 2 3)
The compounds printed in green are formally obtained by epimerization at the indicated positions The L enatiomers are the mirror images at a perpendicular mirror plane
The compounds printed in green are formally obtained by epimerization at the indicated positions The L enatiomers are the mirror images at a perpendicular mirror plane
* can be synthesized from the essential fatty acid linoleic acid Table 1.4-1. Higher Fatty Acids Frequently Occurring in Nature
* can be synthesized from the essential fatty acid linoleic acid Table 1.4-1. Higher Fatty Acids Frequently Occurring in Nature
Table 1.4-2. Common Components of Waxes
Table 1.4-2. Common Components of Waxes
Figure 1.4-3. Classes of Glycerophospholipids
Figure 1.4-3. Classes of Glycerophospholipids
The lipids of the membranes are asymmetrically distributed The flip flop exchange rate to the other membrane side 1s very low (t »= days much higher in bacteria) In human erythrocytes the distribution 1s as follows Transmembrane proteins (integral proteins) span the membrane with & helice of about 19 amino acids These domains contain mostly hydrophobic amin acids which interact with the membrane lipids If the protein contains severa transmembrane domains they can assume a ring lke structure which 1s hydro phobic on the outside and forms a hydrophilic channel at the inside This en ables the passage of hydrophlic compounds through the membrane e g_ for th import of metabolites or 10ns (17 23 1811) Peripheral proteins are attaches by hydrophobic interactions with the membrane lipids or by electrostatic or hy diogen bonds with integral proteins (eg liver cytochrome bs) They can be re moved under relative mild experimental conditions Membrane associated pro teins are bound to the membrane by lipid anchors such as phosphatidylinosito (13 3 4) or 1soprenoids (7 3 4)
The lipids of the membranes are asymmetrically distributed The flip flop exchange rate to the other membrane side 1s very low (t »= days much higher in bacteria) In human erythrocytes the distribution 1s as follows Transmembrane proteins (integral proteins) span the membrane with & helice of about 19 amino acids These domains contain mostly hydrophobic amin acids which interact with the membrane lipids If the protein contains severa transmembrane domains they can assume a ring lke structure which 1s hydro phobic on the outside and forms a hydrophilic channel at the inside This en ables the passage of hydrophlic compounds through the membrane e g_ for th import of metabolites or 10ns (17 23 1811) Peripheral proteins are attaches by hydrophobic interactions with the membrane lipids or by electrostatic or hy diogen bonds with integral proteins (eg liver cytochrome bs) They can be re moved under relative mild experimental conditions Membrane associated pro teins are bound to the membrane by lipid anchors such as phosphatidylinosito (13 3 4) or 1soprenoids (7 3 4)
and by introducing the Michaelis constant Ky Figure 1.5-2. Linear Plots of an Enzyme Catalyzed Reaction
and by introducing the Michaelis constant Ky Figure 1.5-2. Linear Plots of an Enzyme Catalyzed Reaction
Red = uninhibited reaction, blue = inhibited reaction, arrow = shift of the plot at increasing inhibitor concentrations Figure 15-3 Lineweaver-Burk Plots of Inhibited Reactions
Red = uninhibited reaction, blue = inhibited reaction, arrow = shift of the plot at increasing inhibitor concentrations Figure 15-3 Lineweaver-Burk Plots of Inhibited Reactions
The energy required tor its formation 1s called activation energy AG* which can be calculated from this equilibrium by applying Eq [1 5 4] as Arrow = shift of the plot when the concentration of the other substrate is raised “igure 1 5-5 Lineweaver-Burk Plots of Two-Substrate Reactions
The energy required tor its formation 1s called activation energy AG* which can be calculated from this equilibrium by applying Eq [1 5 4] as Arrow = shift of the plot when the concentration of the other substrate is raised “igure 1 5-5 Lineweaver-Burk Plots of Two-Substrate Reactions
Table 2.1-1. Some Typiceal Properties of Living Organisms (Exceptions exist)
Table 2.1-1. Some Typiceal Properties of Living Organisms (Exceptions exist)
Table 2.1-2. Sources of Carbon and of Energy
Table 2.1-2. Sources of Carbon and of Energy
Table 2.1-3. Terminal Electron Acceptors for Oxidation Reactions
Table 2.1-3. Terminal Electron Acceptors for Oxidation Reactions
After Campbell NA Biology 4/e Benjamin/Cummings 1996 The colors are for easy differentiation only
After Campbell NA Biology 4/e Benjamin/Cummings 1996 The colors are for easy differentiation only
Figure 2.2-3. Interrelationship of Rough Endoplasmic Reticulum, Golgi Apparatus, Lysosomes, Endosomes and Transport Vesicles
Figure 2.2-3. Interrelationship of Rough Endoplasmic Reticulum, Golgi Apparatus, Lysosomes, Endosomes and Transport Vesicles
Table 2.2-1. Components of the Cytoskeleton
Table 2.2-1. Components of the Cytoskeleton
Figure 2.2-6 Types of Contact Between Cells Literature.
Figure 2.2-6 Types of Contact Between Cells Literature.
Tertiary structure is a term which refers to larger arrangements, but it cannot be clearly separated from secondary structure ele- ments. In general, it encompasses the following: Figure 2.3-2. a Helix (Top) and Antiparallel B Pleated Sheet Structure (Bottom)
Tertiary structure is a term which refers to larger arrangements, but it cannot be clearly separated from secondary structure ele- ments. In general, it encompasses the following: Figure 2.3-2. a Helix (Top) and Antiparallel B Pleated Sheet Structure (Bottom)
The distances (in nm = = 10 A) ‘and the bond angles ¢ are shown. The green quadrangles indicate the rigid structure of the peptide bonds. ¥ and ® are the angles characterizing the rotation around the C,-CO and N-C, bonds (in this figure ‘¥ = ® = 180°). The formation of hydrogen bonds leading to o helices is indicated.
The distances (in nm = = 10 A) ‘and the bond angles ¢ are shown. The green quadrangles indicate the rigid structure of the peptide bonds. ¥ and ® are the angles characterizing the rotation around the C,-CO and N-C, bonds (in this figure ‘¥ = ® = 180°). The formation of hydrogen bonds leading to o helices is indicated.
* Only the sections are named, where the principle of action is presented. Additional information 1s given in the sections dealing with the individual proteins. Table 2.3-1. Biological Function of Proteins
* Only the sections are named, where the principle of action is presented. Additional information 1s given in the sections dealing with the individual proteins. Table 2.3-1. Biological Function of Proteins
Proteins and peptides play crucial roles in virtually all processes occurring in living cells and organisms. Their functional diversity is represented by the examples in Table 2.3-1. Figure 2.3-4. Examples for Supersecondary Structures
Proteins and peptides play crucial roles in virtually all processes occurring in living cells and organisms. Their functional diversity is represented by the examples in Table 2.3-1. Figure 2.3-4. Examples for Supersecondary Structures
Table 2.4-1. Examples of Cofactors in Enzyme-Catalyzed Reactions Examples of the contribution of enzyme amino acid residues to the catalytic mechanism are shown in Fig 146 | and 14 6 2 (chymotrypsin and pepsin) for the mvolvement of metal atoms in Fig 14 6 3 (carboxypeptidase A) and for a non covalently bound prosthetic group in Figs 42 3 44 2 and 4 4 3 (pyridoxal phosphate) The structure of the intermediate complex of 1 lactate and NAD* with the catalytic center of L lactate dehydrogenase ts shown in Fig 2 4 2
Table 2.4-1. Examples of Cofactors in Enzyme-Catalyzed Reactions Examples of the contribution of enzyme amino acid residues to the catalytic mechanism are shown in Fig 146 | and 14 6 2 (chymotrypsin and pepsin) for the mvolvement of metal atoms in Fig 14 6 3 (carboxypeptidase A) and for a non covalently bound prosthetic group in Figs 42 3 44 2 and 4 4 3 (pyridoxal phosphate) The structure of the intermediate complex of 1 lactate and NAD* with the catalytic center of L lactate dehydrogenase ts shown in Fig 2 4 2
Within a single given species, variants of an enzyme may be pre sent This may be caused by the occurrence of multiple gene loci coding for distinct versions of the enzyme protein, or by the exis tence of multiple alleles at a single gene locus Such variations are designated isoenzymes if they represent multiple forms of the same enzyme activity present in the same species, but are encoded by independent genes Multiple forms of enzymes resulting from different post translational modifications are not true isoenzymes
Within a single given species, variants of an enzyme may be pre sent This may be caused by the occurrence of multiple gene loci coding for distinct versions of the enzyme protein, or by the exis tence of multiple alleles at a single gene locus Such variations are designated isoenzymes if they represent multiple forms of the same enzyme activity present in the same species, but are encoded by independent genes Multiple forms of enzymes resulting from different post translational modifications are not true isoenzymes
2.5.2 Regulation of the Activity of Enzymes (For a Mathematical Treatment see 1.5.4) Dannlatian danandinag am onhocteaota Camneantratinn«s TA tha mance? SECACHICIIE SOO 1.0. F) Regulation depending on substrate concentration: In the most simple case, the dependency of the reaction rate on the substrate concentration according to the Michaelis-Menten equation (Eq. [1.5-19], Fig. 1.5-1) 1s a means of controlling the substrate through- put. Zymogen activation: Some enzymes are synthesized as mactive precursors (zymogens or proenzymes) which have to be processed into their active form by limited proteolysis. Examples are diges- tive enzymes such as chymotrypsinogen or trypsinogen (Fig. 2.5-1) They are synthesized in mammalian pancreas as zymogens. After hormone-controlled release into the small intestine they are irre- versibly processed by trypsin or enteropeptidase, respectively, to become active proteases (Fig. 17.1-11).
2.5.2 Regulation of the Activity of Enzymes (For a Mathematical Treatment see 1.5.4) Dannlatian danandinag am onhocteaota Camneantratinn«s TA tha mance? SECACHICIIE SOO 1.0. F) Regulation depending on substrate concentration: In the most simple case, the dependency of the reaction rate on the substrate concentration according to the Michaelis-Menten equation (Eq. [1.5-19], Fig. 1.5-1) 1s a means of controlling the substrate through- put. Zymogen activation: Some enzymes are synthesized as mactive precursors (zymogens or proenzymes) which have to be processed into their active form by limited proteolysis. Examples are diges- tive enzymes such as chymotrypsinogen or trypsinogen (Fig. 2.5-1) They are synthesized in mammalian pancreas as zymogens. After hormone-controlled release into the small intestine they are irre- versibly processed by trypsin or enteropeptidase, respectively, to become active proteases (Fig. 17.1-11).
The degree of saturation Y Is proportional to the reaction rate in case of allosterically controlled enzymes
The degree of saturation Y Is proportional to the reaction rate in case of allosterically controlled enzymes
Ther influence on reation rates 1s shown In Fig 153
Ther influence on reation rates 1s shown In Fig 153
Covalent modification: Another method of reversible regulation of enzyme activities involves covalent moditications by attach ment or removal of special groups There exist two possibilities
Covalent modification: Another method of reversible regulation of enzyme activities involves covalent moditications by attach ment or removal of special groups There exist two possibilities
Table 2.6-1. Different Forms of the DNA Double Helix
Table 2.6-1. Different Forms of the DNA Double Helix
Figure 2.6-5. Structure of the Nucleosome Core
Figure 2.6-5. Structure of the Nucleosome Core
Figure 2.6-4. Structure of the B-Type DNA Double Helix
Figure 2.6-4. Structure of the B-Type DNA Double Helix
Table 2.6-2. Condensation Levels of Eukaryotic DNA
Table 2.6-2. Condensation Levels of Eukaryotic DNA
Glucose directly enters the main pathway of glycolysis (Fig 3 1-2) by phosphorylation (3 12) Mannose is first phosphorylated and
Glucose directly enters the main pathway of glycolysis (Fig 3 1-2) by phosphorylation (3 12) Mannose is first phosphorylated and
Isomerase and epimerase reactions usually involve the formation of enedio- late intermediates by removal of a proton by a basic group at the enzyme. The reprotonation yields a different product. It is obvious, that this key metabolic pathway has to be strictly regu- lated. In animals, this occurs at many levels (Fig. 3.1-3). Under physiological conditions, the major regulated enzymes glucoki- nase (or hexokinase), phosphofructokinase and pyruvate kinase have restricted flow rates, the substrates pile up to some extent and
Isomerase and epimerase reactions usually involve the formation of enedio- late intermediates by removal of a proton by a basic group at the enzyme. The reprotonation yields a different product. It is obvious, that this key metabolic pathway has to be strictly regu- lated. In animals, this occurs at many levels (Fig. 3.1-3). Under physiological conditions, the major regulated enzymes glucoki- nase (or hexokinase), phosphofructokinase and pyruvate kinase have restricted flow rates, the substrates pile up to some extent and
Dephosphorylation Glucose 6 phosphate 1s transferred to the endo plasmic reticulum ot liver kidney and intestine in a carrier depen dent way and 1s hydrolyzed there The glucose formed returns to the cytosol and 1s secreted into the bloodstream This causes elevation of low blood glucose levels The enzyme 1s inhibited by insulin
Dephosphorylation Glucose 6 phosphate 1s transferred to the endo plasmic reticulum ot liver kidney and intestine in a carrier depen dent way and 1s hydrolyzed there The glucose formed returns to the cytosol and 1s secreted into the bloodstream This causes elevation of low blood glucose levels The enzyme 1s inhibited by insulin
Table 3.1-1. Modulation of Enzyme Expression by Insulin, Catecholamines/cAMP and Glucocorticoids (L = in liver, A = 1n adipose tissue)
Table 3.1-1. Modulation of Enzyme Expression by Insulin, Catecholamines/cAMP and Glucocorticoids (L = in liver, A = 1n adipose tissue)
Figure 3.1-7. Reactions at High (Left) and Low (Right) Glucose Levels
Figure 3.1-7. Reactions at High (Left) and Low (Right) Glucose Levels
combination with the G subunit ( glycogen binding 160 kDa) Phosphoryla tion of the G subunit by an insulin dependent kinase in a way not completely known enables the association and promotes the phosphatase activity If how ever the G subunit becomes phosphorylated at another site by the cAMP de pendent protem kinase A the association of the catalytic and the G subunits 1: prevented and the catalytic subunit remains inactive Phosphorylation: Phosphorylase _b, the usually inactive, phos- phate free form 1s activated by phosphorylation at Ser 14 to phos- phorylase_a (for allosteric interconversions see below) The acti- vating phosphorylase kinase itself 1s activated by phosphorylation, catalyzed by protein kinase A, which 1s cAMP dependent and thus hormone controlled (17 4 2, e g , by epinephrine)
combination with the G subunit ( glycogen binding 160 kDa) Phosphoryla tion of the G subunit by an insulin dependent kinase in a way not completely known enables the association and promotes the phosphatase activity If how ever the G subunit becomes phosphorylated at another site by the cAMP de pendent protem kinase A the association of the catalytic and the G subunits 1: prevented and the catalytic subunit remains inactive Phosphorylation: Phosphorylase _b, the usually inactive, phos- phate free form 1s activated by phosphorylation at Ser 14 to phos- phorylase_a (for allosteric interconversions see below) The acti- vating phosphorylase kinase itself 1s activated by phosphorylation, catalyzed by protein kinase A, which 1s cAMP dependent and thus hormone controlled (17 4 2, e g , by epinephrine)
Table 3.2-1. Hereditary Glycogen Storage Diseases
Table 3.2-1. Hereditary Glycogen Storage Diseases
Figure 3 2-5 Regulation of Glycogen Synthesis and Degradation in Animals (Contrary to the arrow colors in other Figures, red arrows indicate here reactions and regulation mechanisms leading to glycogen synthesis, green arrows leading to glycogen degradation)
Figure 3 2-5 Regulation of Glycogen Synthesis and Degradation in Animals (Contrary to the arrow colors in other Figures, red arrows indicate here reactions and regulation mechanisms leading to glycogen synthesis, green arrows leading to glycogen degradation)
Figure 3 3-1 Reactions of Pyruvate and Phosphoenolpyruvate
Figure 3 3-1 Reactions of Pyruvate and Phosphoenolpyruvate
Figure 3 3-3 Transfer of Compounds Through the Mitochondrial Membrane by the Malate Shuttle 3.3.6 Alcoholic Fermentation Under anaerobic conditions, yeast and a number of bacteria, but also some Aigher plants convert pyruvate to acetaldehyde by the action of pyruvate decarboxylase (Fig 15 4 2) The first step 15 identical with the E, reaction of pyruvate dehydrogenase (3 3 1) Instead of transferring the acyl group of hydroxyethyl ThPP to lipoamide, however, the group 1s eliminated (In Figure 33 4, the actually existing 1onized forms are drawn, while in the main figure the non-1ionized forms are shown ) Acetalde hyde 1s afterwards reduced to ethanol, thus regenerating NAD* This 1s similar to lactate formation in animals under anaerobic conditions
Figure 3 3-3 Transfer of Compounds Through the Mitochondrial Membrane by the Malate Shuttle 3.3.6 Alcoholic Fermentation Under anaerobic conditions, yeast and a number of bacteria, but also some Aigher plants convert pyruvate to acetaldehyde by the action of pyruvate decarboxylase (Fig 15 4 2) The first step 15 identical with the E, reaction of pyruvate dehydrogenase (3 3 1) Instead of transferring the acyl group of hydroxyethyl ThPP to lipoamide, however, the group 1s eliminated (In Figure 33 4, the actually existing 1onized forms are drawn, while in the main figure the non-1ionized forms are shown ) Acetalde hyde 1s afterwards reduced to ethanol, thus regenerating NAD* This 1s similar to lactate formation in animals under anaerobic conditions
Figure 3 4-1 Synthesis and Metabolism of Sucrose
Figure 3 4-1 Synthesis and Metabolism of Sucrose
Figure 3.5-1. Acidic Hexose Derivatives and Inositol
Figure 3.5-1. Acidic Hexose Derivatives and Inositol
The enzymes are present in the cytosol In humans major activities are found in /ner adipose tissue lactating mammary glands adrenal cortex testis thy roid gland and erythrocytes
The enzymes are present in the cytosol In humans major activities are found in /ner adipose tissue lactating mammary glands adrenal cortex testis thy roid gland and erythrocytes
Figure 3.6-3. Formation of C; Compounds by Decarboxylation and Cell Wall Synthesis in Plants
Figure 3.6-3. Formation of C; Compounds by Decarboxylation and Cell Wall Synthesis in Plants
Figure 3 8-1. Interrelations of the Citrate Cycle With Other Metabolic Pathways (blue amino acids, red carbohydrates, green lipids) As described for glycolysis (3.12) the AG, , of the regulated enzymes 1s strongly negative Mayor mechanisms are the inhibitions by NADH (control by the redox state) and by ATP the activations by ADP (control by the energy state ot the cell) and by Ca* (in muscles as a result of muscular activity) Some feedback inhibitions by products also exist Since usually the im ve concentra tions of acetyl CoA and oxaloacetate do not saturate the citrate synthase this enzyme 1s additionally regulated by the avatlability of the substrates
Figure 3 8-1. Interrelations of the Citrate Cycle With Other Metabolic Pathways (blue amino acids, red carbohydrates, green lipids) As described for glycolysis (3.12) the AG, , of the regulated enzymes 1s strongly negative Mayor mechanisms are the inhibitions by NADH (control by the redox state) and by ATP the activations by ADP (control by the energy state ot the cell) and by Ca* (in muscles as a result of muscular activity) Some feedback inhibitions by products also exist Since usually the im ve concentra tions of acetyl CoA and oxaloacetate do not saturate the citrate synthase this enzyme 1s additionally regulated by the avatlability of the substrates
Similar reactions also take place in the cytoplasm of bacteria Their purpose 1s mainly the metabolism of acetate, which 1s taken up from the medium and converted into acety! CoA before entering this pathway In Fscherichia colt isocitrate dehydrogenase (which competes with 1socitrate lyase for the substrate in the same compartment) 1s inactivated by phosphorylation and activated by dephosphorylation of the enzyme (382) The modifying bifunctional kinase/ phosphatase 15 allosterically regulated by intermediates of the citrate cycle which also allostetically regulate the rsocitrate lyase in the opposite direction These mechanisms determine the share of 1socitrate being converted by the citrate and glyoxylate cycles
Similar reactions also take place in the cytoplasm of bacteria Their purpose 1s mainly the metabolism of acetate, which 1s taken up from the medium and converted into acety! CoA before entering this pathway In Fscherichia colt isocitrate dehydrogenase (which competes with 1socitrate lyase for the substrate in the same compartment) 1s inactivated by phosphorylation and activated by dephosphorylation of the enzyme (382) The modifying bifunctional kinase/ phosphatase 15 allosterically regulated by intermediates of the citrate cycle which also allostetically regulate the rsocitrate lyase in the opposite direction These mechanisms determine the share of 1socitrate being converted by the citrate and glyoxylate cycles
Anaerobic or at least microaerobic conditions are required The protection against O in Rhizobium takes place through the symbiontic synthesis of leghe moglobin by the host plant which binds O, with high affinity and releases it in limited quantities to the bacterial membrane (location of the respiratory chain) thus avoiding interference with the nitrogenase activity which 1s located in the cytoplasm (Dotted connections indicate electron transfer reactions
Anaerobic or at least microaerobic conditions are required The protection against O in Rhizobium takes place through the symbiontic synthesis of leghe moglobin by the host plant which binds O, with high affinity and releases it in limited quantities to the bacterial membrane (location of the respiratory chain) thus avoiding interference with the nitrogenase activity which 1s located in the cytoplasm (Dotted connections indicate electron transfer reactions
Bender DA Amino Acid Metabolism 2nd Ed Wilcy (1985) Hayashi H craf Ann Rev of Biochem 59 (1990) 87 110 liaw S_H Eisenberg D Biochemistry 33 (1994) 675 681 Master A Biochem of the Amino Acids 2nd Ed Academic Press (1965) Umbarget HE Ann Rev of Biochem 47 (1978) 522 606
Bender DA Amino Acid Metabolism 2nd Ed Wilcy (1985) Hayashi H craf Ann Rev of Biochem 59 (1990) 87 110 liaw S_H Eisenberg D Biochemistry 33 (1994) 675 681 Master A Biochem of the Amino Acids 2nd Ed Academic Press (1965) Umbarget HE Ann Rev of Biochem 47 (1978) 522 606
Feedback inhibition is indicated by solid arrows repression of enzyme synthesis by dashed arrows | Il and Ill indicate different enzymes with individual regulation 4.5.2 Lysine Metabolism (Fig. 4.5-2) a , — Lysine biosynthesis in bacteria ‘The individual pathway begins with a condensation reaction of aspartate semialdehyde with pyru- vate The product cyclizes immediately After reduction, the non- cyche form 1s stabilized by succinylation or acetylation Further reactions lead to diaminopimelate, which 1s also a component of bacterial cell walls (15 1) By decarboxylation, lystne 15 obtained In some bacteria, a reductive amination leads directly from A!-p1- pertdine 2,6-dicarboxyate to diammopimelate Figure 4.5-1 Regulation of Threonine, Methionine and Lysine Biosynthesis in E. coli Lysine biosynthesis in fungt These organisms use a completely ditferent path way for biosynthesis which originates from 2 oxoglutarate and acetyl CoA The first steps resemble the beginning of the citric acid cycle, employing homolo gous (= homo) compounds The oxoadipate formed undergoes a transamination reaction followed by the reduction to the semialdehyde (possibly via an adeny lylated intermediate) The € amino group 1s not introduced by transamination but rather m a sequence involving reduction, formation of the covalently linked intermediate saccharopme and oxidative Cleavage to yield L lysine This path way 15 regulated by feedback inhibition of the initial condensation reaction
Feedback inhibition is indicated by solid arrows repression of enzyme synthesis by dashed arrows | Il and Ill indicate different enzymes with individual regulation 4.5.2 Lysine Metabolism (Fig. 4.5-2) a , — Lysine biosynthesis in bacteria ‘The individual pathway begins with a condensation reaction of aspartate semialdehyde with pyru- vate The product cyclizes immediately After reduction, the non- cyche form 1s stabilized by succinylation or acetylation Further reactions lead to diaminopimelate, which 1s also a component of bacterial cell walls (15 1) By decarboxylation, lystne 15 obtained In some bacteria, a reductive amination leads directly from A!-p1- pertdine 2,6-dicarboxyate to diammopimelate Figure 4.5-1 Regulation of Threonine, Methionine and Lysine Biosynthesis in E. coli Lysine biosynthesis in fungt These organisms use a completely ditferent path way for biosynthesis which originates from 2 oxoglutarate and acetyl CoA The first steps resemble the beginning of the citric acid cycle, employing homolo gous (= homo) compounds The oxoadipate formed undergoes a transamination reaction followed by the reduction to the semialdehyde (possibly via an adeny lylated intermediate) The € amino group 1s not introduced by transamination but rather m a sequence involving reduction, formation of the covalently linked intermediate saccharopme and oxidative Cleavage to yield L lysine This path way 15 regulated by feedback inhibition of the initial condensation reaction
4.5 Lysine, Threonine, Methionine, Cysteine and Sulfur Metabolism This group of amino acids 1s formed from aspartate Only in fungi lysine originates from 2-oxoglutarate Although cysteine 1s the on- ly one out of this group which 1s not considered essential for mam mals, it still requires the essential amino acid methionine for its synthesis Precursors of isoleucine are both threonine and pyru- vate Its biosynthesis 1s discussed in 4 6 | Figure 4.4-2. Mechanism of Serine Dehydratase 4.5.1 Common Steps of Biosynthesis and Their Regulation (Fig. 4.5-1)
4.5 Lysine, Threonine, Methionine, Cysteine and Sulfur Metabolism This group of amino acids 1s formed from aspartate Only in fungi lysine originates from 2-oxoglutarate Although cysteine 1s the on- ly one out of this group which 1s not considered essential for mam mals, it still requires the essential amino acid methionine for its synthesis Precursors of isoleucine are both threonine and pyru- vate Its biosynthesis 1s discussed in 4 6 | Figure 4.4-2. Mechanism of Serine Dehydratase 4.5.1 Common Steps of Biosynthesis and Their Regulation (Fig. 4.5-1)
A noticeable portion of the intracellularly synthesized glutathione is ex. ported, in animals mostly from liver and kidney. At the outside of the cellular membrane of animals and yeast, GSH transfers its glutamate moiety to aminc Cooper, A.J.L.: Ann. Rev. of Biochem. 52 (1983) 187-222. Meister. A., Anderson, M.E: Ann Rev. of Biochem. 52 (1983) 711-760. Meister, A. J. Biol. Chem. 263 (1988) 17205-17208. Schwenn, J.D.: Z. Naturforsch. 49¢ (1994) 531-539. Umbarver, H.E.: Ann. Rev. of Biochem. 47 (1978) 533-606.
A noticeable portion of the intracellularly synthesized glutathione is ex. ported, in animals mostly from liver and kidney. At the outside of the cellular membrane of animals and yeast, GSH transfers its glutamate moiety to aminc Cooper, A.J.L.: Ann. Rev. of Biochem. 52 (1983) 187-222. Meister. A., Anderson, M.E: Ann Rev. of Biochem. 52 (1983) 711-760. Meister, A. J. Biol. Chem. 263 (1988) 17205-17208. Schwenn, J.D.: Z. Naturforsch. 49¢ (1994) 531-539. Umbarver, H.E.: Ann. Rev. of Biochem. 47 (1978) 533-606.
Figure 4 7-2 Regulation of Aromatic Amino Acid Biosynthesis saturated polyprenyl PP of various lengths (up to n = 15 isoprene units Fig 7 3 2) tollowcd by methylation of the quinol and oxidation to menaquinone (vitamin K ) The plant product phylloguinone 1s synthesized similarly It ditfers in having a phytyl side chain of 4 isoprene units with a single double bond (vitamin K,)
Figure 4 7-2 Regulation of Aromatic Amino Acid Biosynthesis saturated polyprenyl PP of various lengths (up to n = 15 isoprene units Fig 7 3 2) tollowcd by methylation of the quinol and oxidation to menaquinone (vitamin K ) The plant product phylloguinone 1s synthesized similarly It ditfers in having a phytyl side chain of 4 isoprene units with a single double bond (vitamin K,)
This amine 1s synthesized and secreted in pronounced diurnal rhythm and acts as an antagonist to melanotropin (Fig 17 1-4) In mammals it antagonizes the function of the thyroid gland and the secretion of luteinizing hormone (1715) and generally lowers metabolism (‘sleep hormone’) Catabolism of melatonin takes place by hydroxylation and excretion in urine
This amine 1s synthesized and secreted in pronounced diurnal rhythm and acts as an antagonist to melanotropin (Fig 17 1-4) In mammals it antagonizes the function of the thyroid gland and the secretion of luteinizing hormone (1715) and generally lowers metabolism (‘sleep hormone’) Catabolism of melatonin takes place by hydroxylation and excretion in urine
Table 4.7-1. Concentration of Thyroid Hormones in Blood Regulation. All steps of the biosynthesis are regulated by TSH (thyreoglobulin syn thesis 1odination coupling and vacuole formation 17 15)
Table 4.7-1. Concentration of Thyroid Hormones in Blood Regulation. All steps of the biosynthesis are regulated by TSH (thyreoglobulin syn thesis 1odination coupling and vacuole formation 17 15)
Figure 49-1 Urea and Aspartate Cycles, Polyamine and Creatine Synthesis (Biagae gare we se @ N METHYLHYDANTOINASE @N CARBAMOYLSARCOSINE AMIDASE @ GUANIDINOACETATE METHYLTRANSFERASE
Figure 49-1 Urea and Aspartate Cycles, Polyamine and Creatine Synthesis (Biagae gare we se @ N METHYLHYDANTOINASE @N CARBAMOYLSARCOSINE AMIDASE @ GUANIDINOACETATE METHYLTRANSFERASE
Table 4.9-1. Diseases Caused by Deficiencies in Urea Cycle Enzymes Degradation of arginine, as well as of the other urea cycle inter- mediates to glutamate occurs via glutamate semialdehyde by re versal of their biosynthesis (except the phosphorylation step) Deficiencies of all enzymes of the urea cycle have been observed (Table 49 1 combined homozygotic frequencies of these diseases ca 1/25000) They lead to increased blood concentration of their particular substrates but also of their precursors in the cycle as far back as ammonia The primary effect of hy perammonemia ts brain damage
Table 4.9-1. Diseases Caused by Deficiencies in Urea Cycle Enzymes Degradation of arginine, as well as of the other urea cycle inter- mediates to glutamate occurs via glutamate semialdehyde by re versal of their biosynthesis (except the phosphorylation step) Deficiencies of all enzymes of the urea cycle have been observed (Table 49 1 combined homozygotic frequencies of these diseases ca 1/25000) They lead to increased blood concentration of their particular substrates but also of their precursors in the cycle as far back as ammonia The primary effect of hy perammonemia ts brain damage
Figure 5.2-1. Transport and Storage of lron in Higher Animals
Figure 5.2-1. Transport and Storage of lron in Higher Animals
Figure 5 2-5 Oxygen Dissociation Curves for Hemoglobin — (black) and Myoglobin — (red)
Figure 5 2-5 Oxygen Dissociation Curves for Hemoglobin — (black) and Myoglobin — (red)
Using [Mb ] for the total myoglobin concentration [Mb] + |Mb O ] a derivation analogous to the Michaelis Menten equation [Eq 15 19] but without further turnover to products yields
Using [Mb ] for the total myoglobin concentration [Mb] + |Mb O ] a derivation analogous to the Michaelis Menten equation [Eq 15 19] but without further turnover to products yields
Table 5.2-3. Examples of Cytochromes
Table 5.2-3. Examples of Cytochromes
Table 5.2-2. Types of Cy tochromes
Table 5.2-2. Types of Cy tochromes
Jordan PM (Ed) Biosynthesis of Tetrapyrroles New Comprehensive Biochemistry Vol 19 Elsevier (1991)
Jordan PM (Ed) Biosynthesis of Tetrapyrroles New Comprehensive Biochemistry Vol 19 Elsevier (1991)
Table 6.1-1. Differences Between Fatty Acid Biosynthesis and Degradation Mechanisms in Eukarya 6.1.1 Biosynthesis of Fatty Acids
Table 6.1-1. Differences Between Fatty Acid Biosynthesis and Degradation Mechanisms in Eukarya 6.1.1 Biosynthesis of Fatty Acids
Figure 6.1-3. Schematic Drawing of the Animal Fatty Acid Synthase Dimer Reaction sequence (Fig. 6.1-4): Specific acy] transferases (one in animals, two in yeast) transfer an acetyl residue from acetyl-CoA to a cysteine-SH of the 3-oxoacyl synthase component (‘peripheral SH group’) @ and a malonyl residue to the ‘central’ SH group of the ACP component of the multienzyme system. Condensation with an acetoacetyl chain (bound to the central SH group) occurs with simultaneous decarboxylation, thereby energetically favoring chain elongation @). This step is irreversible. Then the resulting C, residue is reduced by NADPH at the oxoacyl reductase component ©, dehydrated to a 2,3-desaturated intermediate @ and reduced again by the enoyl reductase ® (also using NADPH as a reduc- tant; NADH in E.coli). The yeast enzyme contains flavin. Finally, the butyryl chain is transferred to the ‘peripheral’ SH group ©. Condensation with another malonyl! residue initiates another round of chain elongation.
Figure 6.1-3. Schematic Drawing of the Animal Fatty Acid Synthase Dimer Reaction sequence (Fig. 6.1-4): Specific acy] transferases (one in animals, two in yeast) transfer an acetyl residue from acetyl-CoA to a cysteine-SH of the 3-oxoacyl synthase component (‘peripheral SH group’) @ and a malonyl residue to the ‘central’ SH group of the ACP component of the multienzyme system. Condensation with an acetoacetyl chain (bound to the central SH group) occurs with simultaneous decarboxylation, thereby energetically favoring chain elongation @). This step is irreversible. Then the resulting C, residue is reduced by NADPH at the oxoacyl reductase component ©, dehydrated to a 2,3-desaturated intermediate @ and reduced again by the enoyl reductase ® (also using NADPH as a reduc- tant; NADH in E.coli). The yeast enzyme contains flavin. Finally, the butyryl chain is transferred to the ‘peripheral’ SH group ©. Condensation with another malonyl! residue initiates another round of chain elongation.
Figure 6.1-2. Carboxylation of Acetyl-CoA in E. coli
Figure 6.1-2. Carboxylation of Acetyl-CoA in E. coli
Figure 6.1-5. Control Mechanisms for Acetyl-CoA Carboxylase in Liver
Figure 6.1-5. Control Mechanisms for Acetyl-CoA Carboxylase in Liver
Figure 6.1-9. B-Oxidation of Fatty Acids. There are several enzymes catalyzing each step, which differ in their chain-length specificity
Figure 6.1-9. B-Oxidation of Fatty Acids. There are several enzymes catalyzing each step, which differ in their chain-length specificity
Red arrows reactions of long chain acyl derivatives Orange arrows reactions of medium and short chain acyl derivatives Blue arrows Transfer of hydrogen
Red arrows reactions of long chain acyl derivatives Orange arrows reactions of medium and short chain acyl derivatives Blue arrows Transfer of hydrogen
Diacylglycerol can also react with CDP-choline to produce phosphatidylcho- line (lecithin, PC) which, especially in liver, can also be formed from PE by methylation. The regulated step for PC (and likely) PE synthesis is the cytidyly! transferase reaction. The active enzyme is reversibly removed from the mem- brane and this way inactivated by the final product PC or by lack of the sub- strate DG. In addition to phospholipids, cholesterol (7.1.3) and many glycolipids (13.2) including glycoglycerolipids are present in eukaryotic membranes. The contri- bution of the various components to the membrane properties is discussed in 1.4.9. nanan: aaa weet Whereas E. coli possesses a very simple phospholipid composi- tion, consisting primarily of phosphatidylethanolamine, phosphati- dylglycerol and cardiolipin, the phospholipid composition of eu- karyotic membranes is more complex and varies in different tis- sues (Table 6.3-1).
Diacylglycerol can also react with CDP-choline to produce phosphatidylcho- line (lecithin, PC) which, especially in liver, can also be formed from PE by methylation. The regulated step for PC (and likely) PE synthesis is the cytidyly! transferase reaction. The active enzyme is reversibly removed from the mem- brane and this way inactivated by the final product PC or by lack of the sub- strate DG. In addition to phospholipids, cholesterol (7.1.3) and many glycolipids (13.2) including glycoglycerolipids are present in eukaryotic membranes. The contri- bution of the various components to the membrane properties is discussed in 1.4.9. nanan: aaa weet Whereas E. coli possesses a very simple phospholipid composi- tion, consisting primarily of phosphatidylethanolamine, phosphati- dylglycerol and cardiolipin, the phospholipid composition of eu- karyotic membranes is more complex and varies in different tis- sues (Table 6.3-1).
Table 6.3-1. Distribution of Phospholipids (PL) in Various Species (Harwood 1980) length and saturation 15 of crucial importance for the fatty acyl pattern of phos pholipids In eukarya, phosphatidylserine (PS) 1s not formed through the pathway of glycerol activation (except in yeast), but by a base- exchange reaction from PE or PC The catalyzing phosphatidyl- serine synthase requires Ca** and ATP and 1s located in the micro- somes Together with the decarboxylation step of PS this accounts tor the net synthesis of ethanolamine or choline
Table 6.3-1. Distribution of Phospholipids (PL) in Various Species (Harwood 1980) length and saturation 15 of crucial importance for the fatty acyl pattern of phos pholipids In eukarya, phosphatidylserine (PS) 1s not formed through the pathway of glycerol activation (except in yeast), but by a base- exchange reaction from PE or PC The catalyzing phosphatidyl- serine synthase requires Ca** and ATP and 1s located in the micro- somes Together with the decarboxylation step of PS this accounts tor the net synthesis of ethanolamine or choline
Table 6.3-2. Phospholipases
Table 6.3-2. Phospholipases
Table 6.3-3. Selected Cellular Functions Influenced by the Platelet Activating Factor (PAF). See 19 17 204
Table 6.3-3. Selected Cellular Functions Influenced by the Platelet Activating Factor (PAF). See 19 17 204
Cholesterol is a compound of essential importance for animals It 1s an integral member of cellular membranes and influences their fluidity Furthermore, a wealth of biologically active compounds are derived from cholesterol or intermediates of 1ts biosynthesis in various species
Cholesterol is a compound of essential importance for animals It 1s an integral member of cellular membranes and influences their fluidity Furthermore, a wealth of biologically active compounds are derived from cholesterol or intermediates of 1ts biosynthesis in various species
Cyclization starts with an electrophilic attack by the enzyme at C 3 fol lowed by electron shifts The resulting C 20 cation causes a backward rearrangement by H and CH, shifts In case of animals tinally H at C 915 eliminated yielding lanosterol In plants nucleophilic interaction of the en zyme with C 9 causes hydrogen migration from C 9 to C 8 and finally eli mination of H from C 19 with formation of a cyclopropane ring resulting incycloartenol Prokarva cychize squalene to hopanoids (7 2)
Cyclization starts with an electrophilic attack by the enzyme at C 3 fol lowed by electron shifts The resulting C 20 cation causes a backward rearrangement by H and CH, shifts In case of animals tinally H at C 915 eliminated yielding lanosterol In plants nucleophilic interaction of the en zyme with C 9 causes hydrogen migration from C 9 to C 8 and finally eli mination of H from C 19 with formation of a cyclopropane ring resulting incycloartenol Prokarva cychize squalene to hopanoids (7 2)
Cholesterol occurs only rarely in bacteria and plants However they have func tionally related structures (e g hopanoids 7 2)
Cholesterol occurs only rarely in bacteria and plants However they have func tionally related structures (e g hopanoids 7 2)
Table 7.1-1 Cholesterol Distribution (Rat, Weight 341 g). The intracellular ‘cholesterol pool’ (Table 7.1-1) consists of cholesterol esters and free cholesterol. Considerable quantities of esters besides free cholestero! are also present in blood lipopro- teins (18.2), which effect the lipid transport. Mammalian plasma membranes contain 40...50% lipids, /,...’ of which is free cho- lesterol. In intracellular membanes (mitochondria, ER, nucleus), the cholesterol share is lower ('/... 49). Cholesterol esters are prac- tically absent from membranes. However, some precursors of cho- lesterol, such as lathosterol, 7-dehydrocholesterol and desmosterol can be found there. |
Table 7.1-1 Cholesterol Distribution (Rat, Weight 341 g). The intracellular ‘cholesterol pool’ (Table 7.1-1) consists of cholesterol esters and free cholesterol. Considerable quantities of esters besides free cholestero! are also present in blood lipopro- teins (18.2), which effect the lipid transport. Mammalian plasma membranes contain 40...50% lipids, /,...’ of which is free cho- lesterol. In intracellular membanes (mitochondria, ER, nucleus), the cholesterol share is lower ('/... 49). Cholesterol esters are prac- tically absent from membranes. However, some precursors of cho- lesterol, such as lathosterol, 7-dehydrocholesterol and desmosterol can be found there. |
literature
literature
7.2.1 Hopanoids (Figure 7.2-1, left) Late precursors of cholesterol biosynthesis, as well as cholesterol itself, can give rise to a large number of important compounds tor bacteria plants fungt and insects (For early precursors see 7 3 ) ES ee ee ae One These pentacyclic compounds occur in all fossil sediments and petroleum depos its in huge quantities They are widely distributed in prokatya as a membrane component and were found also in some eukarya (e g in the fungus Te frahyme na and in some lugher plants) Apparently thts evolutionary very old gioup of compounds developed at a ttme when the earth atmosphere sull lacked oxygen Whenever the epoxidation of squalene (leading to cholesterol or to cycloarte nol) 1s impossible squalene cyclizes in watcr directly to hopanoids (¢ g diplop tene diplopterol tetrahymenol) Their side chains are then modified with ATP as energy source Frequently polyhydioxylated Cy side chains are found which are attached via ester or amide bonds to sugars amino acids and nucleotides
7.2.1 Hopanoids (Figure 7.2-1, left) Late precursors of cholesterol biosynthesis, as well as cholesterol itself, can give rise to a large number of important compounds tor bacteria plants fungt and insects (For early precursors see 7 3 ) ES ee ee ae One These pentacyclic compounds occur in all fossil sediments and petroleum depos its in huge quantities They are widely distributed in prokatya as a membrane component and were found also in some eukarya (e g in the fungus Te frahyme na and in some lugher plants) Apparently thts evolutionary very old gioup of compounds developed at a ttme when the earth atmosphere sull lacked oxygen Whenever the epoxidation of squalene (leading to cholesterol or to cycloarte nol) 1s impossible squalene cyclizes in watcr directly to hopanoids (¢ g diplop tene diplopterol tetrahymenol) Their side chains are then modified with ATP as energy source Frequently polyhydioxylated Cy side chains are found which are attached via ester or amide bonds to sugars amino acids and nucleotides
Table 7.3-1. Terpenes Dolichol-P (Cj) Cj) 1s an essential sugar carner in animals, plants and fung: for formation of glycoproteins in the endoplasmic reticulum (13 31) Furthermore, dolichyl esters serve as a transport and storage form of fatty acids Cuis-geranylgeranyl-PP enters the pathway to dolichol via a highly affine polyprenyl-crs-transferase Packer L (Ed) Retinoids Part A Methods in Enzymology Vol 189 Academic Press (1990 Zhang FL Casey PJ Ann Rev Biochem 65 (1996) 241 269
Table 7.3-1. Terpenes Dolichol-P (Cj) Cj) 1s an essential sugar carner in animals, plants and fung: for formation of glycoproteins in the endoplasmic reticulum (13 31) Furthermore, dolichyl esters serve as a transport and storage form of fatty acids Cuis-geranylgeranyl-PP enters the pathway to dolichol via a highly affine polyprenyl-crs-transferase Packer L (Ed) Retinoids Part A Methods in Enzymology Vol 189 Academic Press (1990 Zhang FL Casey PJ Ann Rev Biochem 65 (1996) 241 269
Farnesylation takes place if X = serine methionine or glutamine Geranylgerany] 1s attached 1f X = leucine or phenylalanine By Pane EDN ay ar HARES pp eh SMMC DON OSL t ASemmnO RODS BR ce a ee Re is pee Many proteins are attached to cellular membranes by isoprenoid anchors (via a thioether bond to mostly farnesyl, sometimes ge- ranylgeranyl chains), e g Ras (175), G, proteins (17 4) and heme A (521) This prenylation determines the location and the func tron of the proteins The enzymatic reaction 1s shown 1n Fig 7 3-1 IS AUACTIEM TE ZN = IRGC OF POUCH Y taal Proteins of the Rab group which contain -C-C- or C X C-~ sequences ar geranylgeranylated similarly The enzyme 1s assisted by the Rep protein
Farnesylation takes place if X = serine methionine or glutamine Geranylgerany] 1s attached 1f X = leucine or phenylalanine By Pane EDN ay ar HARES pp eh SMMC DON OSL t ASemmnO RODS BR ce a ee Re is pee Many proteins are attached to cellular membranes by isoprenoid anchors (via a thioether bond to mostly farnesyl, sometimes ge- ranylgeranyl chains), e g Ras (175), G, proteins (17 4) and heme A (521) This prenylation determines the location and the func tron of the proteins The enzymatic reaction 1s shown 1n Fig 7 3-1 IS AUACTIEM TE ZN = IRGC OF POUCH Y taal Proteins of the Rab group which contain -C-C- or C X C-~ sequences ar geranylgeranylated similarly The enzyme 1s assisted by the Rep protein
Figure 7 4-3. Regulation of the Synthesis and Secretion of Steroid Hormones (cf Fig 17 1-4)
Figure 7 4-3. Regulation of the Synthesis and Secretion of Steroid Hormones (cf Fig 17 1-4)
Figure 7 4-1 Sites of Steroid Hormone Biosynthesis Reaction types: The major conversions are hydroxylations reductions/isomer izations (usually combined) C_C bond splitting and aromatization (estrogen formation) Frequently the enzymes do not show absolute specificity so that several alternative reacuion sequences can lead to the same end product
Figure 7 4-1 Sites of Steroid Hormone Biosynthesis Reaction types: The major conversions are hydroxylations reductions/isomer izations (usually combined) C_C bond splitting and aromatization (estrogen formation) Frequently the enzymes do not show absolute specificity so that several alternative reacuion sequences can lead to the same end product
In bacteria and plants progesterone biosynthesis proceeds analogously However the conversion of pregnenolone to progesterone 1s performed by 2 separate enzymes Pregnenolone then passes through the mitochondrial membrane and 1s converted by a bifunctional enzyme complex to the gesta- gen hormone, progesterone (Figure 75-1) This reaction takes place at the smooth endoplasmatic reticulum Pregnenolone and progesterone are also the origin of androgens (7 6), estrogens (77), gluco- and mineralocorticoids (7 8), pregnenolone also of cardiac glycosides in plants
In bacteria and plants progesterone biosynthesis proceeds analogously However the conversion of pregnenolone to progesterone 1s performed by 2 separate enzymes Pregnenolone then passes through the mitochondrial membrane and 1s converted by a bifunctional enzyme complex to the gesta- gen hormone, progesterone (Figure 75-1) This reaction takes place at the smooth endoplasmatic reticulum Pregnenolone and progesterone are also the origin of androgens (7 6), estrogens (77), gluco- and mineralocorticoids (7 8), pregnenolone also of cardiac glycosides in plants
Table 7.6-1. Effects of Androgens in Male Vertebrates
Table 7.6-1. Effects of Androgens in Male Vertebrates
Table 7.7-1 Effects of Estrogens m Female Vertebrates
Table 7.7-1 Effects of Estrogens m Female Vertebrates
(Numbers indicate positions of hydroxylation) Figure 7 8-1 Sites Involved in Corticosteroid Synthesis {Numbers tndicate positions of hydroxylation) Table 7.8-2. Diseases Caused by Defects in Corticoid Metabolism
(Numbers indicate positions of hydroxylation) Figure 7 8-1 Sites Involved in Corticosteroid Synthesis {Numbers tndicate positions of hydroxylation) Table 7.8-2. Diseases Caused by Defects in Corticoid Metabolism
Table 7.9-1. Occurence of Bile Acid and Bile Alcohol Conjugates (Examples)
Table 7.9-1. Occurence of Bile Acid and Bile Alcohol Conjugates (Examples)
7.9.1 Occurence (Table 7.9-1) Bile acids are subject to enterohepatic circulation by secretion via the gall bladder into the small intestine (ca 20 30 g/day in humans) and reabsorption 1n the Weum (Fig 18 2-2) This way, about 90 % re- turn via the portal blood to the liver The rest 1s excreted in the feces Bile alcohol derivatives occur only in fishes and amphibia and have frequently 4 or more hydroxy! groups one of which 1s esterified with sulfuric acid C 7 bile acids are found in amphibia and reptiles (except snakes) as taurine conjugates The largest group are the C , bile acids, which are derivatives of 58 cholanic acid (So = allo derivatives are less frequent) Taurine conjugates are widely dis tributed while glycine conjugates occur only in mammals In human bile the ratio of cholic acid / Chenodeoxycholic acid / deoxycholhic acid / lithocholic acid conjugates 1s typically 1/1 /04/ traces
7.9.1 Occurence (Table 7.9-1) Bile acids are subject to enterohepatic circulation by secretion via the gall bladder into the small intestine (ca 20 30 g/day in humans) and reabsorption 1n the Weum (Fig 18 2-2) This way, about 90 % re- turn via the portal blood to the liver The rest 1s excreted in the feces Bile alcohol derivatives occur only in fishes and amphibia and have frequently 4 or more hydroxy! groups one of which 1s esterified with sulfuric acid C 7 bile acids are found in amphibia and reptiles (except snakes) as taurine conjugates The largest group are the C , bile acids, which are derivatives of 58 cholanic acid (So = allo derivatives are less frequent) Taurine conjugates are widely dis tributed while glycine conjugates occur only in mammals In human bile the ratio of cholic acid / Chenodeoxycholic acid / deoxycholhic acid / lithocholic acid conjugates 1s typically 1/1 /04/ traces
8 Nucleotides and Nucleosides phosphates carry additional phosphate residues connected by py- rophosphate-type bonds In cyclic nucleotides, the single phos- phate forms a diester structure with two hydroxyl groups (mostly 3’, 5’) of the pentose Dinucleotides are two nucleotide residues linked by a pyrophosphate bond, eg, NAD* (991) or FAD (93 1) Fig 8 I-1 shows the structures Nucleosides are composed of a purine or pyrimidine base linked to ribose or 2’-deoxyribose (ribo- and deoxyribonucleosides, respec- tively) Nucleotides are usually phosphorylated at the 5’-position ot the pentose morety In a wider sense, structures with other N- contaming ring systems are also named nucleotides, e g , nicotin- amide (9 9 1) or flavin derrvatives (9 3 1) Nucleoside di- and tri-
8 Nucleotides and Nucleosides phosphates carry additional phosphate residues connected by py- rophosphate-type bonds In cyclic nucleotides, the single phos- phate forms a diester structure with two hydroxyl groups (mostly 3’, 5’) of the pentose Dinucleotides are two nucleotide residues linked by a pyrophosphate bond, eg, NAD* (991) or FAD (93 1) Fig 8 I-1 shows the structures Nucleosides are composed of a purine or pyrimidine base linked to ribose or 2’-deoxyribose (ribo- and deoxyribonucleosides, respec- tively) Nucleotides are usually phosphorylated at the 5’-position ot the pentose morety In a wider sense, structures with other N- contaming ring systems are also named nucleotides, e g , nicotin- amide (9 9 1) or flavin derrvatives (9 3 1) Nucleoside di- and tri-
ATP 1s obtained
ATP 1s obtained
effect an increase in reactivity. Example: fatty acid activation (6.1.4). The phosphorylation of proteins can have signalling pur- poses, e.g., in receptor-tyrosine kinase cascades (17.5.3). Hydroly- sis of protein-bound ATP can effect changes in the protein config- uration. Examples: muscle contraction, 17.4.5; ion transport by Na*/K* exchanging ATPase, 18.1.1. groups for the electrons at the bridging oxygen atom The AGj refers to stan- dard conditions (15 1) and varies with the actual concentrations of the reac- tants, the pH and the concentrations of divalent metal 1ons Under physiological conditions, AGpny, 1s in the order of 50 kJ/mol (16 1 1)
effect an increase in reactivity. Example: fatty acid activation (6.1.4). The phosphorylation of proteins can have signalling pur- poses, e.g., in receptor-tyrosine kinase cascades (17.5.3). Hydroly- sis of protein-bound ATP can effect changes in the protein config- uration. Examples: muscle contraction, 17.4.5; ion transport by Na*/K* exchanging ATPase, 18.1.1. groups for the electrons at the bridging oxygen atom The AGj refers to stan- dard conditions (15 1) and varies with the actual concentrations of the reac- tants, the pH and the concentrations of divalent metal 1ons Under physiological conditions, AGpny, 1s in the order of 50 kJ/mol (16 1 1)
Figure 8.1-6. Reaction Mechanism of the Ribonucleoside-Diphosphate Reductase from E. coli
Figure 8.1-6. Reaction Mechanism of the Ribonucleoside-Diphosphate Reductase from E. coli
Figure 8.1-8. Interconversions and Degradation of Purine Deoxyribonucleotides
Figure 8.1-8. Interconversions and Degradation of Purine Deoxyribonucleotides
8.2.3 Ribonucleotide Reduction and Interconversions of Pyrimidine Deoxyribonucleotides (Fig. 8.2-2)
8.2.3 Ribonucleotide Reduction and Interconversions of Pyrimidine Deoxyribonucleotides (Fig. 8.2-2)
Abbreviations Ado adenosine DBI dibenzimidazole SAM _ S adeno sylmethionine SAH = S adenosylhomocysteine THF = tetrahydrofolate E homocysteine methyltransferase /Co/ = corrin ring
Abbreviations Ado adenosine DBI dibenzimidazole SAM _ S adeno sylmethionine SAH = S adenosylhomocysteine THF = tetrahydrofolate E homocysteine methyltransferase /Co/ = corrin ring
Figure 9 5-1. Biosynthesis of Coenzyme B,2 and Conversion of Vitamin B,2 Into the Coenzyme Cobalamin 1s one of the largest non-polymeric biological mole- cules The central cobalt atom 1s coordinated with six ligands Four of them are the pyrrols of the corrin ring, one 1s the unusual nucleotide dimethylbenzimidazole and the sixth can be hydroxyl (vitamin Bj), methyl (methylcobalamin) or 5’-deoxyadenosyl (deoxyadenosylcobalamin, coenzyme B,») In the commercially available form the sixth ligand 1s cyanide
Figure 9 5-1. Biosynthesis of Coenzyme B,2 and Conversion of Vitamin B,2 Into the Coenzyme Cobalamin 1s one of the largest non-polymeric biological mole- cules The central cobalt atom 1s coordinated with six ligands Four of them are the pyrrols of the corrin ring, one 1s the unusual nucleotide dimethylbenzimidazole and the sixth can be hydroxyl (vitamin Bj), methyl (methylcobalamin) or 5’-deoxyadenosyl (deoxyadenosylcobalamin, coenzyme B,») In the commercially available form the sixth ligand 1s cyanide
T iterature
T iterature
9.9.3 Biochemical Function of the Nicotinamide Coenzymes Although the redox potentials of the NAD*/NADH and the NADP*/NADPH systems are almost identical (Ej =-320 and —324 mV) in living organisms a ratio of the oxidized/reduced dinucleotides of about 200 1000 with NAD and 0 01 with NADP 1s maintained
9.9.3 Biochemical Function of the Nicotinamide Coenzymes Although the redox potentials of the NAD*/NADH and the NADP*/NADPH systems are almost identical (Ej =-320 and —324 mV) in living organisms a ratio of the oxidized/reduced dinucleotides of about 200 1000 with NAD and 0 01 with NADP 1s maintained
Literature
Literature
Figure 9 12-1 Oxidation States of Tocopherol and its Function as a Radical Quencher Literature
Figure 9 12-1 Oxidation States of Tocopherol and its Function as a Radical Quencher Literature
Literature
Literature
Figure 9 13-1 Vitamin K Dependent Carboxylation Reactions
Figure 9 13-1 Vitamin K Dependent Carboxylation Reactions
Table 10.1-1 Codon Differences in Mitochondria
Table 10.1-1 Codon Differences in Mitochondria
Table 10.1-2 Codons with Special Functions
Table 10.1-2 Codons with Special Functions
The triplet sequence 1s read from the center outwards The mRNA nucleotide terminology ts shown For DNA nucleotide sequences replace U with T The amino acids are given with their full names and with their three and one letter abbreviations Basic amino acids are shown in blue acidic amino acids in red neutral amino acids in black and amino acids with uncharged polar residues in orange For details see 131
The triplet sequence 1s read from the center outwards The mRNA nucleotide terminology ts shown For DNA nucleotide sequences replace U with T The amino acids are given with their full names and with their three and one letter abbreviations Basic amino acids are shown in blue acidic amino acids in red neutral amino acids in black and amino acids with uncharged polar residues in orange For details see 131
Figure 10 1-2. Information Transfer During Protein Synthesis Since there are 4° = 64 possible nucleotide triplets but only 21 amino acids (including Sec) plus some stop codons (see below) most amino acids are en coded by several nucleotide triplets (synonyms at maximum 6 in the cases of
Figure 10 1-2. Information Transfer During Protein Synthesis Since there are 4° = 64 possible nucleotide triplets but only 21 amino acids (including Sec) plus some stop codons (see below) most amino acids are en coded by several nucleotide triplets (synonyms at maximum 6 in the cases of
Figure 10.2-4. Assembly of the DNA Polymerase Holoenzyme 10.2.5 Kiongation and lerminavion (ig. 1U.2-0, lable 1U.2-2) Gyrase (ATP-dependent topoisomerase type II, breaking and re- ligating both strands) travels along the strands ahead of the helicase and introduces negative supercoils nto the DNA (underwound state of the double helix) This assists the helicase (DnaB) in melting the parental helix by separating the strands The energy 1s derived from simultaneous ATP hydrolysis Reannealing of the strands 1s prevented by the SSB protein cover DNA primase (DnaG), acti-
Figure 10.2-4. Assembly of the DNA Polymerase Holoenzyme 10.2.5 Kiongation and lerminavion (ig. 1U.2-0, lable 1U.2-2) Gyrase (ATP-dependent topoisomerase type II, breaking and re- ligating both strands) travels along the strands ahead of the helicase and introduces negative supercoils nto the DNA (underwound state of the double helix) This assists the helicase (DnaB) in melting the parental helix by separating the strands The energy 1s derived from simultaneous ATP hydrolysis Reannealing of the strands 1s prevented by the SSB protein cover DNA primase (DnaG), acti-
The replication speed in bacteria is about 500 1000 nucleotides/sec (vs 30 50 nucleotides/sec in eukarya) The Escherichia coli chromosome 1s copied in about 40 minutes Cells with doubling times < 40 minutes (e g & coli 20 mi nutes) start another initiation round before the previous replication 1s completed Thus they are partially polyploid (having more than one DNA copy per cell) Figure 10.2-2. Reaction Mechanism of the DNA Replication
The replication speed in bacteria is about 500 1000 nucleotides/sec (vs 30 50 nucleotides/sec in eukarya) The Escherichia coli chromosome 1s copied in about 40 minutes Cells with doubling times < 40 minutes (e g & coli 20 mi nutes) start another initiation round before the previous replication 1s completed Thus they are partially polyploid (having more than one DNA copy per cell) Figure 10.2-2. Reaction Mechanism of the DNA Replication
Figure 10 2-1. Mechanisms of Bacterial Replication Table 10.2-1. Bacterial and Viral Replicons
Figure 10 2-1. Mechanisms of Bacterial Replication Table 10.2-1. Bacterial and Viral Replicons
Table 10.2-2. Proteins Involved in Bacterial DNA Replication (Escherichia coli)
Table 10.2-2. Proteins Involved in Bacterial DNA Replication (Escherichia coli)
The physiological enzymatic methylation of DNA strands however yields N‘ methyladenine, e g within the sequence 5’ GATC 3’ (in bacteria 10 2) or 5 methylcytosine (in eukarya 111) which are not subject to repair mecha nisms Cyclobutylthymidine dimer
The physiological enzymatic methylation of DNA strands however yields N‘ methyladenine, e g within the sequence 5’ GATC 3’ (in bacteria 10 2) or 5 methylcytosine (in eukarya 111) which are not subject to repair mecha nisms Cyclobutylthymidine dimer
a complex, which incises the non-methylated DNA strand 5’ from the GATC site Subsequently, exonucleases degrade the faulty strand from here to a point beyond the site of the lesion If the degradation occurs in 3’ 5’ direction, DNA helicase I, SSB, exonuclease I, DNA polymerase III and DNA ligase take part in repair Degradation in the other direction 1s performed by exonuclease VII or exonuclease RecJ According to the current model, MutS (95 kDa, oligomeric) recognizes the lesion, whereas MutH (25 kDa) binds to a hemimethylated GATC site up to 1000 bp away in either direction Assisted by MutL (95 kDa), the proteins form
a complex, which incises the non-methylated DNA strand 5’ from the GATC site Subsequently, exonucleases degrade the faulty strand from here to a point beyond the site of the lesion If the degradation occurs in 3’ 5’ direction, DNA helicase I, SSB, exonuclease I, DNA polymerase III and DNA ligase take part in repair Degradation in the other direction 1s performed by exonuclease VII or exonuclease RecJ According to the current model, MutS (95 kDa, oligomeric) recognizes the lesion, whereas MutH (25 kDa) binds to a hemimethylated GATC site up to 1000 bp away in either direction Assisted by MutL (95 kDa), the proteins form
Figure 10.3-1. Direct Reversal and Excision DNA Repair Systems in Bacteria (red = damage, green = repair) tween both DNA strands and insures that sequence information for repair 1s retrieved from the unmutated, parental strand.
Figure 10.3-1. Direct Reversal and Excision DNA Repair Systems in Bacteria (red = damage, green = repair) tween both DNA strands and insures that sequence information for repair 1s retrieved from the unmutated, parental strand.
Similar mechanisms (see Figure 10 3 4) are used to fill the gap in the daugh er strand opposite a detective site during replication The defect can be repaired
Similar mechanisms (see Figure 10 3 4) are used to fill the gap in the daugh er strand opposite a detective site during replication The defect can be repaired
Table 10.4-1. Components of the Bacterial RNA Polymerase Holoenzyme
Table 10.4-1. Components of the Bacterial RNA Polymerase Holoenzyme
Figure 10.4-2. Cleavage of the 30S Primary Transcript
Figure 10.4-2. Cleavage of the 30S Primary Transcript
Additional tRNA genes occur in bacterial genomes, often in clus ters Their transcripts are processed the same way
Additional tRNA genes occur in bacterial genomes, often in clus ters Their transcripts are processed the same way
Figure 10 5-3 Activation by CAP Controlled Operons
Figure 10 5-3 Activation by CAP Controlled Operons
ee nnn ee EN I NEI SAE ROE NESE! Only a few regulatory events during the elongation step are known so far The overall RNA chain elongation rate, however, 1s propor tional to the growth rate, ensuring that no excess RNA 1s produced when the translation system operates slowly under conditions of liamited nutritional supply Stringent control: Starvation for an amino acid in bacteria causes a drastic decrease im transcription levels, caused by a signal from the translation step In this stringent contro] mechanism, translat ing ribosomes whose A sites are occupied by non-aminoacylated tRNAs bind the stringent factor enzyme, which then synthesizes the unusual nucleotide guanosine tetraphosphate (PP 5’ G 2’-PP) This compound, 1n turn, reduces transcription of rRNA and tRNA genes (and others) 10- to 20-fold by decreasing the affinity of Pol to the respective promoters via an unresolved mechanism On the other hand, amino acid biosynthesis 1s stimulated
ee nnn ee EN I NEI SAE ROE NESE! Only a few regulatory events during the elongation step are known so far The overall RNA chain elongation rate, however, 1s propor tional to the growth rate, ensuring that no excess RNA 1s produced when the translation system operates slowly under conditions of liamited nutritional supply Stringent control: Starvation for an amino acid in bacteria causes a drastic decrease im transcription levels, caused by a signal from the translation step In this stringent contro] mechanism, translat ing ribosomes whose A sites are occupied by non-aminoacylated tRNAs bind the stringent factor enzyme, which then synthesizes the unusual nucleotide guanosine tetraphosphate (PP 5’ G 2’-PP) This compound, 1n turn, reduces transcription of rRNA and tRNA genes (and others) 10- to 20-fold by decreasing the affinity of Pol to the respective promoters via an unresolved mechanism On the other hand, amino acid biosynthesis 1s stimulated
Table 10.5-2. Examples of Stimulons (E colt)
Table 10.5-2. Examples of Stimulons (E colt)
It should be emphasized that the basic mechanisms of transcrip- tion control outlined above are not mutually exclusive in the regu lation of certain operons, but often are combined or superimposed on each other, allowing still finer tuning of regulation In case of the NtrBC controlled operons (involved in nitrogen assimilation Figure 105 7) it has been shown that NtrB (the sensor kinase) also acts as a specific and regulated phosphatase on NtrC (the response regulator) The actual signal sensed 1s the ratio of 2 oxoglutarate (2 OG)/glutamine (GIn) A low ratio ot 2 OG/GIn (indicating sufficient supply of nitrogen) causes the small protein P II to be deuridylated This activates the phosphatase activity of NuB acting on NtrC Dephosphorylated NtrC in turn does not activate the transcription of NtrC dependent promoters Inversely a high ratio of 2 OG/GIn (signaling nitro gen shortage) causes PII to be uridylated This prevents P II from activating the NuB phosphatase NtrC remains phosphorylated and continues to activate tran scription
It should be emphasized that the basic mechanisms of transcrip- tion control outlined above are not mutually exclusive in the regu lation of certain operons, but often are combined or superimposed on each other, allowing still finer tuning of regulation In case of the NtrBC controlled operons (involved in nitrogen assimilation Figure 105 7) it has been shown that NtrB (the sensor kinase) also acts as a specific and regulated phosphatase on NtrC (the response regulator) The actual signal sensed 1s the ratio of 2 oxoglutarate (2 OG)/glutamine (GIn) A low ratio ot 2 OG/GIn (indicating sufficient supply of nitrogen) causes the small protein P II to be deuridylated This activates the phosphatase activity of NuB acting on NtrC Dephosphorylated NtrC in turn does not activate the transcription of NtrC dependent promoters Inversely a high ratio of 2 OG/GIn (signaling nitro gen shortage) causes PII to be uridylated This prevents P II from activating the NuB phosphatase NtrC remains phosphorylated and continues to activate tran scription
Figure 10 5-6 Regulation by the 2-Component System ArcAB Regulation by Two Component Systems: Usually these systems con sist of a sensor protein and a regulator protein As an example the ArcAB sys tem 1s shown (Fig 105 6) If the respective signal (here a more negative redox state) 1s sensed the sensor protein ArcB autophosphorylates itself at a histidine residue 1n its carboxy terminal domain (which 1s conserved among sensor pro teins) This phosphate 1s then transferred to an aspartate residue in the amino terminal domain of the regulator protein Arc-A This phosphoryl transfer induces a conformational change im ArcA so that it can bind to specific sequences tn the upstream regulator sequence (URS) of all the operons belonging to the same regulon and thus modulate their transcription
Figure 10 5-6 Regulation by the 2-Component System ArcAB Regulation by Two Component Systems: Usually these systems con sist of a sensor protein and a regulator protein As an example the ArcAB sys tem 1s shown (Fig 105 6) If the respective signal (here a more negative redox state) 1s sensed the sensor protein ArcB autophosphorylates itself at a histidine residue 1n its carboxy terminal domain (which 1s conserved among sensor pro teins) This phosphate 1s then transferred to an aspartate residue in the amino terminal domain of the regulator protein Arc-A This phosphoryl transfer induces a conformational change im ArcA so that it can bind to specific sequences tn the upstream regulator sequence (URS) of all the operons belonging to the same regulon and thus modulate their transcription
SRA TN, NN TS RATNER aNICS FEAOTAA: SUNROOM ETE METRE: CNRS Fav eenrne een tANm aw ONE Sar tan CORT Besides the necessity to specifically regulate biosynthetic path- Ways it 1s important to integrate metabolism under the regime of global intra or extracellular signals For this reason up to several dozens of operons can be co regulated by the same regulatory mech anism (stimulons) The 5’ end of the transcribed mRNA contains the code for a short leader pep tide followed by the attenuator sequences | 2 3 4 which can form two alter native secondary structures (12 /3e4 and 23) the first one of which contains a termination hairpin (3e4) If there 1s a sufficient supply of the amino acid trans lating rbosomes (closely following the RNA Pol) proceed to the stop codon at the end of the leader peptide There they cover the first part of the attenuator RNA sequence This allows formation of the terminator hairpin (3e4) and the termination of transcription If on the other hand the level of the particular amino acid 15 low the ribosome translating the leader peptide ts delayed earlier at sever al consecutive codons for this sparse amino acid (e g 2 * UGG for tryptophan) This leaves the attenuator sequence temporarily uncovered and allows the forma tion of the alternative secondary structure 2e3 which does not contain the termi nator hairpin Therefore transcription can proceed through the structural genes and the enzymes tor biosynthesis of this amino acid are produced
SRA TN, NN TS RATNER aNICS FEAOTAA: SUNROOM ETE METRE: CNRS Fav eenrne een tANm aw ONE Sar tan CORT Besides the necessity to specifically regulate biosynthetic path- Ways it 1s important to integrate metabolism under the regime of global intra or extracellular signals For this reason up to several dozens of operons can be co regulated by the same regulatory mech anism (stimulons) The 5’ end of the transcribed mRNA contains the code for a short leader pep tide followed by the attenuator sequences | 2 3 4 which can form two alter native secondary structures (12 /3e4 and 23) the first one of which contains a termination hairpin (3e4) If there 1s a sufficient supply of the amino acid trans lating rbosomes (closely following the RNA Pol) proceed to the stop codon at the end of the leader peptide There they cover the first part of the attenuator RNA sequence This allows formation of the terminator hairpin (3e4) and the termination of transcription If on the other hand the level of the particular amino acid 15 low the ribosome translating the leader peptide ts delayed earlier at sever al consecutive codons for this sparse amino acid (e g 2 * UGG for tryptophan) This leaves the attenuator sequence temporarily uncovered and allows the forma tion of the alternative secondary structure 2e3 which does not contain the termi nator hairpin Therefore transcription can proceed through the structural genes and the enzymes tor biosynthesis of this amino acid are produced
Table 10.6-2. Translation Factors in E. coli (Figure 10.6-4) 10.6.2 Aminoacylation of tRNAs (Figure 10.6-3)
Table 10.6-2. Translation Factors in E. coli (Figure 10.6-4) 10.6.2 Aminoacylation of tRNAs (Figure 10.6-3)
Figure 10.6-3. Aminoacylation of tRNAs (by Class II Ligases) Each ligase 1s highly specific for a single amino acid. They aminoacy- late all tRNAs specific for the same amino acid (isoacceptor-tRNAs, see “genetic code’, 10.1).
Figure 10.6-3. Aminoacylation of tRNAs (by Class II Ligases) Each ligase 1s highly specific for a single amino acid. They aminoacy- late all tRNAs specific for the same amino acid (isoacceptor-tRNAs, see “genetic code’, 10.1).
Figure 10.6-2. Structure of the Bacterial Ribosome
Figure 10.6-2. Structure of the Bacterial Ribosome
no 1soenzy me in which cysteine substitutes selenocysteine 1s known Table 10.6-3. Proteins Containing Selenocysteine (Selection)
no 1soenzy me in which cysteine substitutes selenocysteine 1s known Table 10.6-3. Proteins Containing Selenocysteine (Selection)
In eukarya and archaea, the corresponding special MRNA struc- ture 15 located in the 3’ untranslated region of the transcript
In eukarya and archaea, the corresponding special MRNA struc- ture 15 located in the 3’ untranslated region of the transcript
Fig 10 6-5 Principle of Ribosomal Protein Synthesis
Fig 10 6-5 Principle of Ribosomal Protein Synthesis
Table 11.1-2. Essentials for Initiation of DNA Replication in Yeast (Saccharomyces cerevisiae)
Table 11.1-2. Essentials for Initiation of DNA Replication in Yeast (Saccharomyces cerevisiae)
Figure 11.1-1 Phases of the Eukaryotic Cell Cycle The mechanisms underlying these controls are only partially known More details of the regulatory aspects are given in Section 11 6 DNA replication must be precisely linked to the cell cycle (sum marized in Fig 11 1-1) It depends on the passage through a spe- cial point in the G,_phase, at which cells commit to another round of replication and cell division (see below) DNA 1s replicated exclu- sively mm the S-phase For the next round of replication, a passage through the M phase must have taken place
Figure 11.1-1 Phases of the Eukaryotic Cell Cycle The mechanisms underlying these controls are only partially known More details of the regulatory aspects are given in Section 11 6 DNA replication must be precisely linked to the cell cycle (sum marized in Fig 11 1-1) It depends on the passage through a spe- cial point in the G,_phase, at which cells commit to another round of replication and cell division (see below) DNA 1s replicated exclu- sively mm the S-phase For the next round of replication, a passage through the M phase must have taken place
* A different nomenclature for veast used by some authors 1s added in parentheses Two other non essential polymerases (PolV 120 135 kDa and Pol Rev 3/Rev7 173 kDa) have also been described in yeast Table t1.1-3. Eukaryotic DNA Polymerases
* A different nomenclature for veast used by some authors 1s added in parentheses Two other non essential polymerases (PolV 120 135 kDa and Pol Rev 3/Rev7 173 kDa) have also been described in yeast Table t1.1-3. Eukaryotic DNA Polymerases
replication Their sequences are highly conserved (human and yeast DNA polymerase a show 31%, bovine and yeast DNA poly- merase 6 44% homology)
replication Their sequences are highly conserved (human and yeast DNA polymerase a show 31%, bovine and yeast DNA poly- merase 6 44% homology)
Figure 11.1-6. Eukaryotic DNA Replication (Details not completely known)
Figure 11.1-6. Eukaryotic DNA Replication (Details not completely known)
Table 11.2-1. Protein Factors in Eukaryotic Nucleotide Excision Repair (Selection)
Table 11.2-1. Protein Factors in Eukaryotic Nucleotide Excision Repair (Selection)
Table 11.3-1. Lukaryotic Nuclear RNA Polymerases The basic components of the transcriptional machinery were well conserved in evolution The order of the transcription complex wsembly is basically the s ime for yeast, Drosophila and humans The (wo large polymerase subumits are cven homo lozous to the two largest subunits of the E coli RNA polymerase (10 4 1) Transcription 1s performed by DNA-duected RNA polymer ases Unlike DNA polymerases, RNA polymerases do not need a primer to start the reaction While bacteria contain only one RNA polymerase (104 1) there are three different RNA poly merases in cukaryotic cells which transcribe different genes All these polymerases are multisubunit complexes two large polypeptides (ca 200 and 140 kDa) are associated with about 12 smaller subunits, some of which are common to all three enzymes Additionally, there are different Pol in mitochondria and chloroplasts
Table 11.3-1. Lukaryotic Nuclear RNA Polymerases The basic components of the transcriptional machinery were well conserved in evolution The order of the transcription complex wsembly is basically the s ime for yeast, Drosophila and humans The (wo large polymerase subumits are cven homo lozous to the two largest subunits of the E coli RNA polymerase (10 4 1) Transcription 1s performed by DNA-duected RNA polymer ases Unlike DNA polymerases, RNA polymerases do not need a primer to start the reaction While bacteria contain only one RNA polymerase (104 1) there are three different RNA poly merases in cukaryotic cells which transcribe different genes All these polymerases are multisubunit complexes two large polypeptides (ca 200 and 140 kDa) are associated with about 12 smaller subunits, some of which are common to all three enzymes Additionally, there are different Pol in mitochondria and chloroplasts
Figure 11 3-4 Splicing Mechanism for mRNA Besides this mechanism (group III introns) other splicing mechanisms exist They proceed with an external guanosine nucleotide instead of the branching point A (group I rRNA) or with a hgation procedure after endonuclease split ting of the pre mRNA (group [IV tRNA) Splicing of group II introns (e g muito chondria and chloroplast mRNA) resembles the group If] mechanism but with out participation of snRNPs Frequently the group I or I procedures are per tormed by RNA activity only (self splicing e g rRNA in Tetrahymena) Exon ot ditterent RNA strands can also be combined by splicing mechanisms (trans splicing e g MRNA 1n Trypanosoma)
Figure 11 3-4 Splicing Mechanism for mRNA Besides this mechanism (group III introns) other splicing mechanisms exist They proceed with an external guanosine nucleotide instead of the branching point A (group I rRNA) or with a hgation procedure after endonuclease split ting of the pre mRNA (group [IV tRNA) Splicing of group II introns (e g muito chondria and chloroplast mRNA) resembles the group If] mechanism but with out participation of snRNPs Frequently the group I or I procedures are per tormed by RNA activity only (self splicing e g rRNA in Tetrahymena) Exon ot ditterent RNA strands can also be combined by splicing mechanisms (trans splicing e g MRNA 1n Trypanosoma)
Table 11.3-4. Transcription Factors for RNA Polymerase I
Table 11.3-4. Transcription Factors for RNA Polymerase I
Table 11.3-3. Some Factors Involved in Mammalian Polyadenylation
Table 11.3-3. Some Factors Involved in Mammalian Polyadenylation
Figure 11 3-5 Polyadenylation of mRNA
Figure 11 3-5 Polyadenylation of mRNA
bases per molecule eg methylated or dimethylated A, U C or € residues and pseudo uridine (‘P) TFIIB/Pol Il intuation complex 15 very stable and may pass through many rounds of tRNA transcription Transcription and elongation sturt immediately after assembly of the initiation complex The transcription of snRNA U6 (11 3 4) proceeds similarly
bases per molecule eg methylated or dimethylated A, U C or € residues and pseudo uridine (‘P) TFIIB/Pol Il intuation complex 15 very stable and may pass through many rounds of tRNA transcription Transcription and elongation sturt immediately after assembly of the initiation complex The transcription of snRNA U6 (11 3 4) proceeds similarly
Table 11.3-5. Transcription Factors for RNA Polymerase III
Table 11.3-5. Transcription Factors for RNA Polymerase III
Table 11 4-1. Examples of Domains mm Transcription Factors
Table 11 4-1. Examples of Domains mm Transcription Factors
Figure 11 4-4 Examples of RNA polymerase II! core promoters
Figure 11 4-4 Examples of RNA polymerase II! core promoters
RNA polymerase I core promoters (Fig. 11.4-3): RNA poly- merase I promoters (and the vast majority of RNA polymerase III] promoters) lack TATA boxes The core promoter (in mammals and amphibians) consists of two critically spaced sequences the upstream control element (UCE, location at -200 -—100 nucleo tides from the start site) and the core region (location at-50 +20 nucleotides therefore enclosing the start site) Only little tran scriptional control 1s exerted on pre-rRNA synthesis
RNA polymerase I core promoters (Fig. 11.4-3): RNA poly- merase I promoters (and the vast majority of RNA polymerase III] promoters) lack TATA boxes The core promoter (in mammals and amphibians) consists of two critically spaced sequences the upstream control element (UCE, location at -200 -—100 nucleo tides from the start site) and the core region (location at-50 +20 nucleotides therefore enclosing the start site) Only little tran scriptional control 1s exerted on pre-rRNA synthesis
Table 11.4-2, Examples of Eukaryotic Enhancers and Repressor Elements * Less conserved bases are printed with lower case letters ** TPA (12 O tetradecanoyl phorbol 13 acetate) 1s a potent tumor promoter potentiating the effect of a subcarcinogenic dose of an initiating carcinogen
Table 11.4-2, Examples of Eukaryotic Enhancers and Repressor Elements * Less conserved bases are printed with lower case letters ** TPA (12 O tetradecanoyl phorbol 13 acetate) 1s a potent tumor promoter potentiating the effect of a subcarcinogenic dose of an initiating carcinogen
The specific transcription factors have to be activated by binding of ligands or by phosphorylation in order to bind to their target DNA sites Some examples for this mechanism are shown 1n Fig 1146 For steroid receptors, see Section 17 6
The specific transcription factors have to be activated by binding of ligands or by phosphorylation in order to bind to their target DNA sites Some examples for this mechanism are shown 1n Fig 1146 For steroid receptors, see Section 17 6
Eukaryotic mRNAs apparently lack a sequence like the bacterial Shine Dal garno Sequence (1063) which 1s specifically recognized by the ribosome Consequently they are mostly monocistronic (coding for only | gene)
Eukaryotic mRNAs apparently lack a sequence like the bacterial Shine Dal garno Sequence (1063) which 1s specifically recognized by the ribosome Consequently they are mostly monocistronic (coding for only | gene)
Regulation of Cyclin-CDK Activity (Fig. 11.6-2): Cyclins share a conserved sequence of 100 amino acids called the cyclin box which interacts with the CDK subunit This associtation causes a conformational change within the CDK which leads to partial activation of CDKs A subsequent phosphorylation of a key threonine residue (T160 1n mammalian CDK2) by a CDK activating kinase (CAK Table 11 6 1) 1s required for full activation and stabilization of the cyclin CDK complex The active complex then catalyzes the phosphoryla tion of a number of substrates leading to cell cycle progression
Regulation of Cyclin-CDK Activity (Fig. 11.6-2): Cyclins share a conserved sequence of 100 amino acids called the cyclin box which interacts with the CDK subunit This associtation causes a conformational change within the CDK which leads to partial activation of CDKs A subsequent phosphorylation of a key threonine residue (T160 1n mammalian CDK2) by a CDK activating kinase (CAK Table 11 6 1) 1s required for full activation and stabilization of the cyclin CDK complex The active complex then catalyzes the phosphoryla tion of a number of substrates leading to cell cycle progression
# Elf ! = Lymphoid specific transcription factor association with Rb blocks G, exit * ATF 2 — Activating transcription factor 2 (Table 175 3) °c Abl = Transcnpton fact promotes the phosphorylation of the CTD domain of RNA Pol IE (Table 17 5 3) @ Mdm2 — Mouse double minute 2 § UBF = Upstream binding tactor enhances Pol I tran scription (11 4 1) Upon mitogenic stimulation by hormones (17 5 1), D type cyclins are induced during the first part of the G, phase and assemble with their catalytic counterparts, the cyclin dependent kinases CDK4 and CDK 6 For further activation, the cyclin D-CDK complexes must be additionally phosphorylated on a single threonine residue by a CDK activating kinase (CAK, 11 6 1) The expression of cyclin E peaks at the G, — S transition This expression 15 stimulated by free E2F forming a positive feedback loop Following entry into S phase cyclin A CDK2 phosphorylates the DP | component of the E2F DP1 heterodimer This inhibits its DNA binding ability and thus stops further expres
# Elf ! = Lymphoid specific transcription factor association with Rb blocks G, exit * ATF 2 — Activating transcription factor 2 (Table 175 3) °c Abl = Transcnpton fact promotes the phosphorylation of the CTD domain of RNA Pol IE (Table 17 5 3) @ Mdm2 — Mouse double minute 2 § UBF = Upstream binding tactor enhances Pol I tran scription (11 4 1) Upon mitogenic stimulation by hormones (17 5 1), D type cyclins are induced during the first part of the G, phase and assemble with their catalytic counterparts, the cyclin dependent kinases CDK4 and CDK 6 For further activation, the cyclin D-CDK complexes must be additionally phosphorylated on a single threonine residue by a CDK activating kinase (CAK, 11 6 1) The expression of cyclin E peaks at the G, — S transition This expression 15 stimulated by free E2F forming a positive feedback loop Following entry into S phase cyclin A CDK2 phosphorylates the DP | component of the E2F DP1 heterodimer This inhibits its DNA binding ability and thus stops further expres
Table 11.6-2. Functional Analogies/Homologies Between Cell Cycle Proteins
Table 11.6-2. Functional Analogies/Homologies Between Cell Cycle Proteins
DNA replication (11.1) yields pairs of sister_chromatids that are linked to each other at the centromere DNA section (ca. 110 bp in yeast, much longer in mammals). Protein complexes (kinetochores) assemble on either side of the centromeres during metaphase.
DNA replication (11.1) yields pairs of sister_chromatids that are linked to each other at the centromere DNA section (ca. 110 bp in yeast, much longer in mammals). Protein complexes (kinetochores) assemble on either side of the centromeres during metaphase.
For the precise timing and order of events during the cell cycle, control mechanisms (checkpoints) have to ensure that an earlier event 1s completed before starting a later event
For the precise timing and order of events during the cell cycle, control mechanisms (checkpoints) have to ensure that an earlier event 1s completed before starting a later event
Replication via a RNA intermediate which undergoes reverse transcription
Replication via a RNA intermediate which undergoes reverse transcription
Cann AJ Principles cf Modern Virology Academic Press (1993) Levine AJ Viruses Scientific American Library (1992) Riesner D Gross HJ Ann Rev of Biochem 54 (1985) 531 564 Voyles BA The Biology cf Viruses Mosby (1993) Viruses can be classified according to their genome and their mode of replication as DNA RNA- and retroviruses The genomic nucleic acids can be single- (ss) or double stranded (ds) Single stranded viruses are subdivided into (+)viruses (their nucleic acid 1s analogous to MRNA and to the coding = nontranscribed strand Literature 12.1.1 Genomic Characteristics Since the host organisms have developed a variety of antiviral defense sys tems (e g restriction endonucleases in bacteria complex immune system in ver tebrates) viruses responded by evolutionary strategies to escape these control mechanisms either by fast and massive replication or by persistent and latent in fections Still smaller are viroids which consist of a single stranded covalently closed RNA of 250 400 nt with multiple base pairing but without a protein content They reproduce in plants by using host proteins (perhaps DNA directed RNA polymerase II 11 3 2) and have pathogenic effects An example 1s potato spin dle tuber viroid Usually the genomic nucleic acid 1s surrounded by a protein coat (capsid) This consists of multiple copies of onc or a few proteins and 1s arranged in the shape ot a cylinder or of a regular icosahedron In many cases some enzyme proteins ire associated with the nucleic acid More complex viruses have additionally a pid membrane (envelope which originates from the cellular membrane of the nost with interspersed viral proteins) or specialized tails etc Some of the most important families of viruses are listed in Table 12 1 | Due to the large variety ot viruses It 1s only possible to discuss one representative of each group on the following pages
Cann AJ Principles cf Modern Virology Academic Press (1993) Levine AJ Viruses Scientific American Library (1992) Riesner D Gross HJ Ann Rev of Biochem 54 (1985) 531 564 Voyles BA The Biology cf Viruses Mosby (1993) Viruses can be classified according to their genome and their mode of replication as DNA RNA- and retroviruses The genomic nucleic acids can be single- (ss) or double stranded (ds) Single stranded viruses are subdivided into (+)viruses (their nucleic acid 1s analogous to MRNA and to the coding = nontranscribed strand Literature 12.1.1 Genomic Characteristics Since the host organisms have developed a variety of antiviral defense sys tems (e g restriction endonucleases in bacteria complex immune system in ver tebrates) viruses responded by evolutionary strategies to escape these control mechanisms either by fast and massive replication or by persistent and latent in fections Still smaller are viroids which consist of a single stranded covalently closed RNA of 250 400 nt with multiple base pairing but without a protein content They reproduce in plants by using host proteins (perhaps DNA directed RNA polymerase II 11 3 2) and have pathogenic effects An example 1s potato spin dle tuber viroid Usually the genomic nucleic acid 1s surrounded by a protein coat (capsid) This consists of multiple copies of onc or a few proteins and 1s arranged in the shape ot a cylinder or of a regular icosahedron In many cases some enzyme proteins ire associated with the nucleic acid More complex viruses have additionally a pid membrane (envelope which originates from the cellular membrane of the nost with interspersed viral proteins) or specialized tails etc Some of the most important families of viruses are listed in Table 12 1 | Due to the large variety ot viruses It 1s only possible to discuss one representative of each group on the following pages
———_—reros Adhya SI etal Progr Nucl Acid Res Mol Biol 26 (1981) 103 11 Das A Ann Rev of Biochem 62 (1993) 908 918 Herskowitz I Hagen D Ann Rev of Genetics 14 (1980) 399-445 Murialdo H Ann Rev of Biochem 60 (1991) 125—153
———_—reros Adhya SI etal Progr Nucl Acid Res Mol Biol 26 (1981) 103 11 Das A Ann Rev of Biochem 62 (1993) 908 918 Herskowitz I Hagen D Ann Rev of Genetics 14 (1980) 399-445 Murialdo H Ann Rev of Biochem 60 (1991) 125—153
Infection of the bacterial cell (Figure 12.2-3): Adsorption to the E colt host cell takes place via specific interaction of the phage tai] fiber and a maltose group of the bacterial outer membrane Then the phage DNA 1s injected through the tail into the host cell The linear DNA 1s transformed into a cyclic form, whereupon the host DNA ligase closes the phage genome ring covalently and the DNA gyrase produces supercoiled phage DNA Now the phage enters one of two different states
Infection of the bacterial cell (Figure 12.2-3): Adsorption to the E colt host cell takes place via specific interaction of the phage tai] fiber and a maltose group of the bacterial outer membrane Then the phage DNA 1s injected through the tail into the host cell The linear DNA 1s transformed into a cyclic form, whereupon the host DNA ligase closes the phage genome ring covalently and the DNA gyrase produces supercoiled phage DNA Now the phage enters one of two different states
Figure 12.3-2. Systemic Infection by TMV Passage Through Plasmodesmata
Figure 12.3-2. Systemic Infection by TMV Passage Through Plasmodesmata
The initiation complex for reverse transcription [consisting of the viral enzyme reverse transcriptase (RT), the nucleocapsid pro- teins and the viral primer t-RNA] 1s being activated by the viral
The initiation complex for reverse transcription [consisting of the viral enzyme reverse transcriptase (RT), the nucleocapsid pro- teins and the viral primer t-RNA] 1s being activated by the viral
Figure 12.4-2. Mechanism of HIV Pteplication (red arrows: virus reactions, blue arrows: host reactions) @® Viral t-RNA‘S? primer is an- nealed to the primer binding site (PBS, length 18 nucleotides).
Figure 12.4-2. Mechanism of HIV Pteplication (red arrows: virus reactions, blue arrows: host reactions) @® Viral t-RNA‘S? primer is an- nealed to the primer binding site (PBS, length 18 nucleotides).
The structures of the saccharide chains are generally determined by enzyme action and not by genetic matrices The glycan chains are bound to asparagine and sometimes to the e€-group of lysine (N-glycosylation) or to serine or threonine, occasionally also to 5- hydroxylysine, hydroxyproline or tyrosine (O-glycosylation) In eukarya, the N-glycosylation of glycoproteins and proteoglycans begins 1n the endoplasmic reticulum (13 3) and 1s continued in the Golgi apparatus (13 4), while the O-glycosylation usually starts in the Golg: The transport between the various cellular compart- ments and to the cell surface proceeds via vesicles (14 2) In some cases, specific carbohydrate sequences ‘target’ the glycoprotein to its destination (e g terminal mannose 6-phosphate guides to lyso- somes (1421) In its absence due to a genetic defect, the glyco- protein 1s secreted I-cell disease) Glycosylated derivatives of proteins and peptides (as well as of lipids) play a major role in cellular metabolism and recognition
The structures of the saccharide chains are generally determined by enzyme action and not by genetic matrices The glycan chains are bound to asparagine and sometimes to the e€-group of lysine (N-glycosylation) or to serine or threonine, occasionally also to 5- hydroxylysine, hydroxyproline or tyrosine (O-glycosylation) In eukarya, the N-glycosylation of glycoproteins and proteoglycans begins 1n the endoplasmic reticulum (13 3) and 1s continued in the Golgi apparatus (13 4), while the O-glycosylation usually starts in the Golg: The transport between the various cellular compart- ments and to the cell surface proceeds via vesicles (14 2) In some cases, specific carbohydrate sequences ‘target’ the glycoprotein to its destination (e g terminal mannose 6-phosphate guides to lyso- somes (1421) In its absence due to a genetic defect, the glyco- protein 1s secreted I-cell disease) Glycosylated derivatives of proteins and peptides (as well as of lipids) play a major role in cellular metabolism and recognition
Figure 13.1-2. Schematized Structure of Proteoglycans
Figure 13.1-2. Schematized Structure of Proteoglycans
Similar structure to heparin but with more N acetyl groups and less O or N attached sulfate groups 5*10* 12*10*? Da Ubiquitously present at cell surfaces and laminae Lack of sulfamidase for degradation = Santilippo s syndrome A Lack of @N acetylhexosamidase = Sanfilippo s syndrome B (mucopolysacchart dosis HT) Like heparin it inhibits blood coagulation (20 3)
Similar structure to heparin but with more N acetyl groups and less O or N attached sulfate groups 5*10* 12*10*? Da Ubiquitously present at cell surfaces and laminae Lack of sulfamidase for degradation = Santilippo s syndrome A Lack of @N acetylhexosamidase = Sanfilippo s syndrome B (mucopolysacchart dosis HT) Like heparin it inhibits blood coagulation (20 3)
[pb glucuronate (2 sulfate) (a1— 4) N sulfo b glucosamine (6 sulfate) (&@1— 4)] (mostly) HEPARIN 6* 10> 25*10'Da contains also some D-Gal and b xylose Large quantities are found in mast cells lung and liver Heparin ts an in hibitor of blood coagulation (20 3) by promoting complex forma tion between active proteases (Ila [Xa, Xa) and antithrombin II]
[pb glucuronate (2 sulfate) (a1— 4) N sulfo b glucosamine (6 sulfate) (&@1— 4)] (mostly) HEPARIN 6* 10> 25*10'Da contains also some D-Gal and b xylose Large quantities are found in mast cells lung and liver Heparin ts an in hibitor of blood coagulation (20 3) by promoting complex forma tion between active proteases (Ila [Xa, Xa) and antithrombin II]
4*10* 8*10° Da Large quantities in connective tissues shin, cartilage synovial fluid Hyaluromec acid forms the backbone of many proteoglycans Eg in the proteoglycan of cartilage core proteins (which bear side chains of keratan sulfate and chondroitin sulfate) are non covalently attached to hyaluronic acid with their N terminus The binding site 1s stabilized with linker proteins (Fig 13 1 2)
4*10* 8*10° Da Large quantities in connective tissues shin, cartilage synovial fluid Hyaluromec acid forms the backbone of many proteoglycans Eg in the proteoglycan of cartilage core proteins (which bear side chains of keratan sulfate and chondroitin sulfate) are non covalently attached to hyaluronic acid with their N terminus The binding site 1s stabilized with linker proteins (Fig 13 1 2)
Table 13.2-3. Gangliosides in Mammals Gangliosides of other series occur in lower animals. They mediate interactions between cells and with the extracellular matrix, cell-cell communication, immunological functions, leukocyte differentiation, oncogenic reactions etc During embryogenesis and thereafter, the ganglioside pattern changes Gangliosides (and other glycosphingolipids) influence cell dif- ferentiation and the development of the neuronal network Biosynthesis: Ceramide 1s synthesized in the endoplasmic reticu- lum (6.3.4). The primary glycosylation steps, which take place mainly in the Golgi apparatus, are described in 13.4. They are analogous to the biosynthesis of glycosylated proteins by ligand transfer from XDP-sugars, XDP-aminosugars or CMP-sialic acid to ceramide.
Table 13.2-3. Gangliosides in Mammals Gangliosides of other series occur in lower animals. They mediate interactions between cells and with the extracellular matrix, cell-cell communication, immunological functions, leukocyte differentiation, oncogenic reactions etc During embryogenesis and thereafter, the ganglioside pattern changes Gangliosides (and other glycosphingolipids) influence cell dif- ferentiation and the development of the neuronal network Biosynthesis: Ceramide 1s synthesized in the endoplasmic reticu- lum (6.3.4). The primary glycosylation steps, which take place mainly in the Golgi apparatus, are described in 13.4. They are analogous to the biosynthesis of glycosylated proteins by ligand transfer from XDP-sugars, XDP-aminosugars or CMP-sialic acid to ceramide.
Table 13.2-1. Types of Glycolipids 13.2.1 Glycosphingolipids Similar to many glycosylated proteins (13.1), glycolipids are members of the glycocalyx layer covering the cellular membrane The lipid part forms the anchor in the membrane (Figure 13.2-1), to which the (frequently antigenically reactive) glycosidic chain 1s bound Three different types are distinguished (Table 13.2-1): Glycosphingolipids occur in vertebrates and lower animals, as mi- nor components in plants and (only rarely) in bacteria.
Table 13.2-1. Types of Glycolipids 13.2.1 Glycosphingolipids Similar to many glycosylated proteins (13.1), glycolipids are members of the glycocalyx layer covering the cellular membrane The lipid part forms the anchor in the membrane (Figure 13.2-1), to which the (frequently antigenically reactive) glycosidic chain 1s bound Three different types are distinguished (Table 13.2-1): Glycosphingolipids occur in vertebrates and lower animals, as mi- nor components in plants and (only rarely) in bacteria.
Many diverse structures exist, they are species and organ specific Some of them vary with age They are classified by the type of the 3 sugars next to the lipid moiety (‘root structure’, Table 13 2-2) Frequently they carry acidic groups (sulfate, uronic acids, sialic acid etc ) In membranes they tend to aggregate Gangliosides are glycosphingolipids, which also contain sialic acid (N-acetylneuramuinic acid or its 9-O acetyl derivative in humans, addi- tional derivatives in other mammals, fish, birds etc.). They are found primarily in the central nervous system, but also in other organs of vertebrates at the outer side of the plasma membrane (Table 12.2-3).
Many diverse structures exist, they are species and organ specific Some of them vary with age They are classified by the type of the 3 sugars next to the lipid moiety (‘root structure’, Table 13 2-2) Frequently they carry acidic groups (sulfate, uronic acids, sialic acid etc ) In membranes they tend to aggregate Gangliosides are glycosphingolipids, which also contain sialic acid (N-acetylneuramuinic acid or its 9-O acetyl derivative in humans, addi- tional derivatives in other mammals, fish, birds etc.). They are found primarily in the central nervous system, but also in other organs of vertebrates at the outer side of the plasma membrane (Table 12.2-3).
Examples only, many variants exist For basic structures, see Fig 13 4 1) Figure 13.2-2. Synthesis of Higher Gangliosides
Examples only, many variants exist For basic structures, see Fig 13 4 1) Figure 13.2-2. Synthesis of Higher Gangliosides
Table 13 3-1 Components of Protemn Processing in the ER Table 13 3-2 Enzymes Involved in Glycosylation Reactions in the ER Synthesis of glycosylphosphatidylinositol (GPD) in eukarya The syn thesis starts at the outside of the ER by adding N acetylglucosamine residues from UDP GIcNAc to phosphatidylinositol (6 3 2) followed by deacylation The question of whether the following transfer of 3 mannoses take place at the outside or the inside of the ER membrane 1s still under discussion Phosphoethanolamine 1s finally added possibly from phosphatidylethanolamine (6 3 2) This structure may be modified by the addition of more mannose residues or galactosyl side chains to the core carbohydrates or of fatty acids to mositol etc Myristoylated proteins bind to specific membrane receptors and become membrane attached this way Palmitoylation (mostly of a cysteine close to the N terminus) however takes place posttrans- lationally at locations outside of the ER This reversible reaction may play a role in regulation (e g of receptors and of G proteins 1741) C numbers in parentheses)
Table 13 3-1 Components of Protemn Processing in the ER Table 13 3-2 Enzymes Involved in Glycosylation Reactions in the ER Synthesis of glycosylphosphatidylinositol (GPD) in eukarya The syn thesis starts at the outside of the ER by adding N acetylglucosamine residues from UDP GIcNAc to phosphatidylinositol (6 3 2) followed by deacylation The question of whether the following transfer of 3 mannoses take place at the outside or the inside of the ER membrane 1s still under discussion Phosphoethanolamine 1s finally added possibly from phosphatidylethanolamine (6 3 2) This structure may be modified by the addition of more mannose residues or galactosyl side chains to the core carbohydrates or of fatty acids to mositol etc Myristoylated proteins bind to specific membrane receptors and become membrane attached this way Palmitoylation (mostly of a cysteine close to the N terminus) however takes place posttrans- lationally at locations outside of the ER This reversible reaction may play a role in regulation (e g of receptors and of G proteins 1741) C numbers in parentheses)
Figure 13 3-1 Protein Processing in the Endoplasmic Reticulurr * Bip — binding, protein (Hsp70) ATPase function present in the lumen of the ER
Figure 13 3-1 Protein Processing in the Endoplasmic Reticulurr * Bip — binding, protein (Hsp70) ATPase function present in the lumen of the ER
Figure 13.4-2. Synthesis of Glycoproteins in the Golgi Apparatus
Figure 13.4-2. Synthesis of Glycoproteins in the Golgi Apparatus
Table 14.1-2. Chaperones Involved in Protein Folding in the ER Literature
Table 14.1-2. Chaperones Involved in Protein Folding in the ER Literature
Bergeron Jy M etal Trends in Biochem Sci 19 (1994) 124 128 Friedman RB ctal Trends in Biochem Sci 19 (1994) 331-333 Frydman J cta/ Nature 370 (1994) 111 117 Hartl FU etal Trends in Biochem Sci 19 (1994) 20-25 Mayhew M Hartl FU Science 271 (1996) 161 162 For many proteins the consecutive folding of the molten globule into its final tertiary structure takes place inside of the GroEL/ES complex The folding pro cess requires a sequence of binding steps and final release of the polypeptide It 1s dependent on ATP
Bergeron Jy M etal Trends in Biochem Sci 19 (1994) 124 128 Friedman RB ctal Trends in Biochem Sci 19 (1994) 331-333 Frydman J cta/ Nature 370 (1994) 111 117 Hartl FU etal Trends in Biochem Sci 19 (1994) 20-25 Mayhew M Hartl FU Science 271 (1996) 161 162 For many proteins the consecutive folding of the molten globule into its final tertiary structure takes place inside of the GroEL/ES complex The folding pro cess requires a sequence of binding steps and final release of the polypeptide It 1s dependent on ATP
Table 14.1-1. Molecular Chaperones and Enzymes Involved in Protein Folding in E_ cols and Homologues in Eukarya
Table 14.1-1. Molecular Chaperones and Enzymes Involved in Protein Folding in E_ cols and Homologues in Eukarya
Table 14.2-1. Proteins With Functions in the Intra-Golgi Transport System
Table 14.2-1. Proteins With Functions in the Intra-Golgi Transport System
The spatial arrangement and the sequence of some steps have not been exactly demonstrated The nomenclature for vertebrates is used
The spatial arrangement and the sequence of some steps have not been exactly demonstrated The nomenclature for vertebrates is used
Table 14.4-1. Components for Import into Mitochondria
Table 14.4-1. Components for Import into Mitochondria
Table 14.5-1. Components for Import into Chloroplasts
Table 14.5-1. Components for Import into Chloroplasts
T iterature
T iterature
Table 15.2-1. Factors Involved in Protein Export of Escherichia coli Literature: SECU ES COLUEE We Economou, A etal Cell 83 (1995) 1171-1188 Lutcke, H Eur J Biochem 228 (1995) 531-550 Randall, L L , Hardy, S JS Trends in Biochem Sei 20 (1995) 65-69 Wolin, SL Cell 77 (1994) 787-790 Wickner. WT Science 266 (1994) 1197-1198
Table 15.2-1. Factors Involved in Protein Export of Escherichia coli Literature: SECU ES COLUEE We Economou, A etal Cell 83 (1995) 1171-1188 Lutcke, H Eur J Biochem 228 (1995) 531-550 Randall, L L , Hardy, S JS Trends in Biochem Sei 20 (1995) 65-69 Wolin, SL Cell 77 (1994) 787-790 Wickner. WT Science 266 (1994) 1197-1198
Figure 15.3-1. Examples for Bacterial Transport Systems
Figure 15.3-1. Examples for Bacterial Transport Systems
cn in both tables refer only to the energy metabolism Due to inabohe reactions the actual yield of end products 15 lowe: Table 15.4-1. Fermentation of Sugars (Examples)
cn in both tables refer only to the energy metabolism Due to inabohe reactions the actual yield of end products 15 lowe: Table 15.4-1. Fermentation of Sugars (Examples)
Figure 15 4-1 General Principle of Fermentation Only some specialized fermentations eg diacetyl fermentation by Leu ono stoc spec have been tound to involve ton transport mechanisms These gener During fermentation ATP can only be generated by substrate level _phos phorylation This results in quite a low ATP yield and therefore requires a high substrate throughput Eg in homolactate fermentation 2 mol ATP are obtained trom 1 mol glucose while aerobic respiration theoretically results in 33 mol ATP and about 29 mol ATP under practical conditions (see 3 8 3 and 16 | 1)
Figure 15 4-1 General Principle of Fermentation Only some specialized fermentations eg diacetyl fermentation by Leu ono stoc spec have been tound to involve ton transport mechanisms These gener During fermentation ATP can only be generated by substrate level _phos phorylation This results in quite a low ATP yield and therefore requires a high substrate throughput Eg in homolactate fermentation 2 mol ATP are obtained trom 1 mol glucose while aerobic respiration theoretically results in 33 mol ATP and about 29 mol ATP under practical conditions (see 3 8 3 and 16 | 1)
Figure 15.4-4. Fermentations of Nitrogeneous Compounds (For Other Bacterial Degradations of Amino Acids, see Chapter 4).
Figure 15.4-4. Fermentations of Nitrogeneous Compounds (For Other Bacterial Degradations of Amino Acids, see Chapter 4).
Diacetyl fermentation from citrate (Lactococcus spec Leuconostoc spec )
Diacetyl fermentation from citrate (Lactococcus spec Leuconostoc spec )
Figure 15.5-3. Acetate formation (e g in Clostridium thermoaceticum)
Figure 15.5-3. Acetate formation (e g in Clostridium thermoaceticum)
Reduction of CO (oxidation state +4) to CH, (—4) occurs in several steps The carbon atom remains covalently bound to special one carbon carriers At first CO 1s reduced to the formyl group (+2) bound to methanofuran The for myl group 1s transferred to tetrahydromethanopterin (H; MPT THMPT 965) Water 15 subtracted to yield the methenyl group which 1s then reduced to the methylene level (0) The 5_deazaflavin coenzyme F, (9 3 2) serves as electron carrier from the hydrogenase Further reduction (involving F, ) yields methyl H, MPT ( 2) from which the methyl group 1s transferred to coenzyme M (2 mercaploethanesulfonic acid) The resulting methyl CoM 1s reduced to meth ane the nickel porphinoid coenzyme Fy, (9 5 3) serves as cofactor The actual reductant 1s 7 mercaptoheptanoylthreonine phosphate (HS HTP coenzyme B) which 15 oxidized and forms a heterodisultide with coenzyme M The reduced DiMarco AA eta/ Ann Rev Biochem 59 (1990) 355 394 Ferry JG (Ed) Methanogenensts Chapman & Hall (1993)
Reduction of CO (oxidation state +4) to CH, (—4) occurs in several steps The carbon atom remains covalently bound to special one carbon carriers At first CO 1s reduced to the formyl group (+2) bound to methanofuran The for myl group 1s transferred to tetrahydromethanopterin (H; MPT THMPT 965) Water 15 subtracted to yield the methenyl group which 1s then reduced to the methylene level (0) The 5_deazaflavin coenzyme F, (9 3 2) serves as electron carrier from the hydrogenase Further reduction (involving F, ) yields methyl H, MPT ( 2) from which the methyl group 1s transferred to coenzyme M (2 mercaploethanesulfonic acid) The resulting methyl CoM 1s reduced to meth ane the nickel porphinoid coenzyme Fy, (9 5 3) serves as cofactor The actual reductant 1s 7 mercaptoheptanoylthreonine phosphate (HS HTP coenzyme B) which 15 oxidized and forms a heterodisultide with coenzyme M The reduced DiMarco AA eta/ Ann Rev Biochem 59 (1990) 355 394 Ferry JG (Ed) Methanogenensts Chapman & Hall (1993)
* These reactions proceed from reduced to oxidized state ** Calculated trom AE, or from free energies of formation per mole of substrate oxidize
* These reactions proceed from reduced to oxidized state ** Calculated trom AE, or from free energies of formation per mole of substrate oxidize
Figure 15.6-2 Redox Potentials E4[mV, 25 °C, pH = 7 0] of Substrate Couples
Figure 15.6-2 Redox Potentials E4[mV, 25 °C, pH = 7 0] of Substrate Couples
Figure 15.6-5 Reversed Electron Flow Driven by the Electro- chemical Gradient
Figure 15.6-5 Reversed Electron Flow Driven by the Electro- chemical Gradient
Table 15 8-1. Classification of Antibiotics (AB) (acc to Berdy 1985)
Table 15 8-1. Classification of Antibiotics (AB) (acc to Berdy 1985)
cline leads to formation of oxytetracycline Some steps of the biosynthetic pathway have not been clarified yet Resistances’ Resistances of bacteria are mostly due to modification of the tar get site ot the antibiotic (e g MLS resistance by N° dimethylation of the base 2058 of 23 S rRNA) Biosynthesis’ The biosynthesis of macrolides proceeds via the polykctide pathway To | molecule of propionyl CoA 6 units of 2 methylmalony! CoA are consecutively added During eich condensation step 1 C atom 1s eliminated via CO. Apart from the lack of reductive steps these reactions resemble those of the fatty acid synthesis (6 1 1) From the instable intermediates upon ring clo Resistances Tetracycline enters bicteria by an active transport mechanism through the cyfoplasmi membrane The major mechanisms of resistance are decieased uptake and active transport out of the cells
cline leads to formation of oxytetracycline Some steps of the biosynthetic pathway have not been clarified yet Resistances’ Resistances of bacteria are mostly due to modification of the tar get site ot the antibiotic (e g MLS resistance by N° dimethylation of the base 2058 of 23 S rRNA) Biosynthesis’ The biosynthesis of macrolides proceeds via the polykctide pathway To | molecule of propionyl CoA 6 units of 2 methylmalony! CoA are consecutively added During eich condensation step 1 C atom 1s eliminated via CO. Apart from the lack of reductive steps these reactions resemble those of the fatty acid synthesis (6 1 1) From the instable intermediates upon ring clo Resistances Tetracycline enters bicteria by an active transport mechanism through the cyfoplasmi membrane The major mechanisms of resistance are decieased uptake and active transport out of the cells
Malonamoyl! CoA 1s formed tiom aspatagine vid L oxosuccinamate (4 2 4) Fazvyme bound malonamoyl CoA 15 condensed with malonyl CoA (formed from acetate 51) Consecutively 7 more malonyl CoA units are added with the climination of | C atom as CO in each step The first intermedi ite 15 6 me thylpretetramide which has been demonstrated by the use of block mutants At ter hydroxylation and oxidation reactions 4 dedimethylamino 4 oxo anhydro tetracycline ts a branch point of the biosynthetic pathway Halogenation by chloride haloperoxidase leads via several following steps to chlorotctracycline For formation of tetracyclines an amino group 1s introduccd followed by the addition of 2 methyl groups and subsequent hydroxylation and reduction reac tions Another branch of the pathway at the stage of 5a (11a) dehydro tetracy
Malonamoyl! CoA 1s formed tiom aspatagine vid L oxosuccinamate (4 2 4) Fazvyme bound malonamoyl CoA 15 condensed with malonyl CoA (formed from acetate 51) Consecutively 7 more malonyl CoA units are added with the climination of | C atom as CO in each step The first intermedi ite 15 6 me thylpretetramide which has been demonstrated by the use of block mutants At ter hydroxylation and oxidation reactions 4 dedimethylamino 4 oxo anhydro tetracycline ts a branch point of the biosynthetic pathway Halogenation by chloride haloperoxidase leads via several following steps to chlorotctracycline For formation of tetracyclines an amino group 1s introduccd followed by the addition of 2 methyl groups and subsequent hydroxylation and reduction reac tions Another branch of the pathway at the stage of 5a (11a) dehydro tetracy
Table 16.1-1. Complexes of the Respiratory Chain in Mammahan Mitochondria Complex I performs the oxidation of NADH It consists of a pe ripheral part extending into the mitochondrial matrix, which con- tams FMN and all FeS clusters and an extremely lipophilic part. which 1s embedded tn the membrane Apparently the FeS centers transmit the electrons from the NADH oxidation to a putative qui-
Table 16.1-1. Complexes of the Respiratory Chain in Mammahan Mitochondria Complex I performs the oxidation of NADH It consists of a pe ripheral part extending into the mitochondrial matrix, which con- tams FMN and all FeS clusters and an extremely lipophilic part. which 1s embedded tn the membrane Apparently the FeS centers transmit the electrons from the NADH oxidation to a putative qui-
16.1.2 Electron Transport System in Mitochondria (Fig.16.1-1) The respiratory chain consists of 3 multienzyme complexes and succinate dehydrogenase (Table 16 1 1), which (except succinate dehydrogenase) are transmembrane proteins of the imner mito chondrial membrane They contain as active redox components flavin mononucleotides, iron sulfur proteins, cytochromes (5 2 4) and Cu centers
16.1.2 Electron Transport System in Mitochondria (Fig.16.1-1) The respiratory chain consists of 3 multienzyme complexes and succinate dehydrogenase (Table 16 1 1), which (except succinate dehydrogenase) are transmembrane proteins of the imner mito chondrial membrane They contain as active redox components flavin mononucleotides, iron sulfur proteins, cytochromes (5 2 4) and Cu centers
the matrix side. The UQH, enters the quinone pool and is turned over as described above, resulting 1n release of 2 more H* into the cytosol. none (X), which is involved in pumping of 4 H* to the cytosol as well as in reduction of 1 ubiquinone (UQ, 4.7.2) to ubihydroqui- none (ubiguinol) (UQH,) per | NADH oxidized. The UQH, then enters the so-called quinone pool within the membrane, which transports by diffusion hydrogen from complexes I and II (see be- low) to complex III.
the matrix side. The UQH, enters the quinone pool and is turned over as described above, resulting 1n release of 2 more H* into the cytosol. none (X), which is involved in pumping of 4 H* to the cytosol as well as in reduction of 1 ubiquinone (UQ, 4.7.2) to ubihydroqui- none (ubiguinol) (UQH,) per | NADH oxidized. The UQH, then enters the so-called quinone pool within the membrane, which transports by diffusion hydrogen from complexes I and II (see be- low) to complex III.
Table 16.1-3. Complexes of the ATP Synthase
Table 16.1-3. Complexes of the ATP Synthase
Table 16.1-2. Compl es of the Respiratory Chain in Escherichia coli
Table 16.1-2. Compl es of the Respiratory Chain in Escherichia coli
Table 16.2-1. Composition of the Light Harvesting Complexes (LHC)
Table 16.2-1. Composition of the Light Harvesting Complexes (LHC)
>90 % efficiency) to the reaction center. In photosytem IJ of plants and Cyanobacteria or in the only reaction center of purple bacte- ria, it excites a pigment special pair, which in turn donates an electron extremely fast to a primary acceptor (pheophytine, 5.4 or bacteriochlorphyll, 5.4), causing the reaction to become irreversi- ble. The electron finally reaches phylloquinone B (PQs, 4 7.2) or ubiguinone B (UQs, 4.7.2), respectively, where 2 electrons and 2 protons (from the cytoplasm) accumulate, forming a hydroquinone (quinol) (Fig. 16.2-5).
>90 % efficiency) to the reaction center. In photosytem IJ of plants and Cyanobacteria or in the only reaction center of purple bacte- ria, it excites a pigment special pair, which in turn donates an electron extremely fast to a primary acceptor (pheophytine, 5.4 or bacteriochlorphyll, 5.4), causing the reaction to become irreversi- ble. The electron finally reaches phylloquinone B (PQs, 4 7.2) or ubiguinone B (UQs, 4.7.2), respectively, where 2 electrons and 2 protons (from the cytoplasm) accumulate, forming a hydroquinone (quinol) (Fig. 16.2-5).
In vivo, the actual potentials can differ due to protein binding variant concentration ratios etc Fig 16 2-6 Standard Redox Potentials in Photosynthesis (Purple Bacteria/Plants and Cyanobacteria)
In vivo, the actual potentials can differ due to protein binding variant concentration ratios etc Fig 16 2-6 Standard Redox Potentials in Photosynthesis (Purple Bacteria/Plants and Cyanobacteria)
Regeneration of the reaction center: In plants and cyanobacte ria, the ‘special pair’ P680* replaces the lost electron by abstrac- tion of another electron from a Mn,-protemn complex (oxygen evolving complex, OEC) via a tyrosine residue, Z After 4 repeats, OEC* reacts with water and 1s reduced again
Regeneration of the reaction center: In plants and cyanobacte ria, the ‘special pair’ P680* replaces the lost electron by abstrac- tion of another electron from a Mn,-protemn complex (oxygen evolving complex, OEC) via a tyrosine residue, Z After 4 repeats, OEC* reacts with water and 1s reduced again
T iterature
T iterature
Figure 16 2-9 Carboxylase (Top) and Oxygenase (Below) Reaction Mechanisms of Rubisco Regulation of the Calym cycle The cycle has to operate only tf sufficient NADPH and ATP trom the hght reaction are available in order to prevent useless degradation reactions This 1s performed by light induced activation of rubisco fructose bisphosphatase (FBPase) and sedoheptulose bisphosphatase (SBPasc)
Figure 16 2-9 Carboxylase (Top) and Oxygenase (Below) Reaction Mechanisms of Rubisco Regulation of the Calym cycle The cycle has to operate only tf sufficient NADPH and ATP trom the hght reaction are available in order to prevent useless degradation reactions This 1s performed by light induced activation of rubisco fructose bisphosphatase (FBPase) and sedoheptulose bisphosphatase (SBPasc)
Figure 16.2-10. CO, Pumping by the C, Cycie (NADP*-Malate Enzyme Type, e.g. in Maize and Sugar Cane Figure 16.2-8. CO, Fixation by the Calvin Cycle and its Regulation
Figure 16.2-10. CO, Pumping by the C, Cycie (NADP*-Malate Enzyme Type, e.g. in Maize and Sugar Cane Figure 16.2-8. CO, Fixation by the Calvin Cycle and its Regulation
cAMP ctivates PKA this promotes the uptake of Ci into the 7 plasmic reticulum (17 44) and decre ises the cyicsolee Ca concentration which controls contration Addition uly myosin light cham kinase ts phosphorylated and deac uvited (17 4 5) Table 17 1 2 Metabolic Effects of Catecholamines
cAMP ctivates PKA this promotes the uptake of Ci into the 7 plasmic reticulum (17 44) and decre ises the cyicsolee Ca concentration which controls contration Addition uly myosin light cham kinase ts phosphorylated and deac uvited (17 4 5) Table 17 1 2 Metabolic Effects of Catecholamines
Puberty marks the beginning of the menstrual cycle with a charac teristic pattern of the plasma hormone fluctuations (Fig 17 1 6), which are additionally modulated by the diurnal pulsating secrets ons This periodicity 1s regulated by a complicated interplay of forward activations and feedback inhibitions within the hormone cascade
Puberty marks the beginning of the menstrual cycle with a charac teristic pattern of the plasma hormone fluctuations (Fig 17 1 6), which are additionally modulated by the diurnal pulsating secrets ons This periodicity 1s regulated by a complicated interplay of forward activations and feedback inhibitions within the hormone cascade
Figure 17 1-6. Hormone Concentration in Plasma During the Menstrual Cycle
Figure 17 1-6. Hormone Concentration in Plasma During the Menstrual Cycle
Table 17.1-3. Concentration of Na* and K* Ions
Table 17.1-3. Concentration of Na* and K* Ions
Figure 17.1-8. Fiow Sheet of Calcium in an Adult Human (70 kg)
Figure 17.1-8. Fiow Sheet of Calcium in an Adult Human (70 kg)
Gastric hormones (Fig.17.1-10): Neuronal impulses (acetylcho- line, or from the parasympathetic neurons gastrin releasing pep- tide), as well as signals from the stomach (high pH value, stretch- ing) promote the secretion of gastrin, which causes release of HCl into the stomach The same neuronal impulses inhibit the secretion of somatostatin, which blocks the HCI release
Gastric hormones (Fig.17.1-10): Neuronal impulses (acetylcho- line, or from the parasympathetic neurons gastrin releasing pep- tide), as well as signals from the stomach (high pH value, stretch- ing) promote the secretion of gastrin, which causes release of HCl into the stomach The same neuronal impulses inhibit the secretion of somatostatin, which blocks the HCI release
Figure 17 2-1 Generation of the Action Potential Figure 17 2-2 Protein Segments of Voltage Gated Nat and Ca** fon Channels (« subunit, additionally there are several other sub units) In the K Channel there are 4 separate o protein chains
Figure 17 2-1 Generation of the Action Potential Figure 17 2-2 Protein Segments of Voltage Gated Nat and Ca** fon Channels (« subunit, additionally there are several other sub units) In the K Channel there are 4 separate o protein chains
The characteristics of neuronal transmission and of neurotrans- mitters are compiled mn Tables 17 2 1,172 2 and 172 3
The characteristics of neuronal transmission and of neurotrans- mitters are compiled mn Tables 17 2 1,172 2 and 172 3
Table 17.2-3. Agonists and Antagonists for Postsynaptic Receptors 17.2.6 Axonal Transport (Table 17.2-4) Literature: i ee The receptors are divided in many subtypes Agonists and antagonists perform transmitter-specrfic actions with different affinities to the receptors This allows discrimination of the receptors in pharmacological and toxicological studies and development of specific pharma- ceuticals A selection of them, including synthetic compounds of high specificity 15 listed below Maintenance of neuronal function requires continuous supply of metabolites trom the cell body to the nerve terminal and vice ver- sa Axonal transport occurs along tracks formed by microtubules and by the smooth endoplasmic reticulum (18 13) East_axonal transport 1s rapidly established by the microtubuli associated ATPases dynein (MAPIC) and kinesin, which act as motor mole- cules Alkaloids, which disrupt microtubuli (e g. vinblastin and colchicine) block this process immediately. In contrast to this, slow axonal transport involves physical translocation of the cyto- skeleton It provides mainly cytoskeletal elements for the nerve terminal.
Table 17.2-3. Agonists and Antagonists for Postsynaptic Receptors 17.2.6 Axonal Transport (Table 17.2-4) Literature: i ee The receptors are divided in many subtypes Agonists and antagonists perform transmitter-specrfic actions with different affinities to the receptors This allows discrimination of the receptors in pharmacological and toxicological studies and development of specific pharma- ceuticals A selection of them, including synthetic compounds of high specificity 15 listed below Maintenance of neuronal function requires continuous supply of metabolites trom the cell body to the nerve terminal and vice ver- sa Axonal transport occurs along tracks formed by microtubules and by the smooth endoplasmic reticulum (18 13) East_axonal transport 1s rapidly established by the microtubuli associated ATPases dynein (MAPIC) and kinesin, which act as motor mole- cules Alkaloids, which disrupt microtubuli (e g. vinblastin and colchicine) block this process immediately. In contrast to this, slow axonal transport involves physical translocation of the cyto- skeleton It provides mainly cytoskeletal elements for the nerve terminal.
Table 17.2-4. Components and Characteristics of Axonal Transport
Table 17.2-4. Components and Characteristics of Axonal Transport
Figure 17 3-1 Receptors and Intracellular Transmission of Messages
Figure 17 3-1 Receptors and Intracellular Transmission of Messages
Figure 17 4-1 Activation Mechanism by G,-Proteins
Figure 17 4-1 Activation Mechanism by G,-Proteins
Table 17.4-1. Mammalian G, Proteins (For indirectly gating nerve transmission systems, compare Table 17.2-2)
Table 17.4-1. Mammalian G, Proteins (For indirectly gating nerve transmission systems, compare Table 17.2-2)
Table 17.4-2. Mammalian Gg, Proteins (Tightly Associated Complexes) Membrane anchored_ * by farnesy] at C terminal serine # by geranylgeranyl at C terminal leucine Also known B, B; ¥,(# pairs with B, and 8B, widespread occurrence) y;(# pairs with B and B widespread occurrence) y; (# pairs with B, and B) widespread occurrence) ys # in olfactory epithelium) y , G# pairs with B, and B.) y (* similar to y, pairs with B widespread occurrence)
Table 17.4-2. Mammalian Gg, Proteins (Tightly Associated Complexes) Membrane anchored_ * by farnesy] at C terminal serine # by geranylgeranyl at C terminal leucine Also known B, B; ¥,(# pairs with B, and 8B, widespread occurrence) y;(# pairs with B and B widespread occurrence) y; (# pairs with B, and B) widespread occurrence) ys # in olfactory epithelium) y , G# pairs with B, and B.) y (* similar to y, pairs with B widespread occurrence)
Literature: Fischer, E.H.: Angew. Chem. 105 (1993) 1181-1188 (Nobel Prize Lecture) Walsh, D.A., van Patten. S.M.: FASEB J. 8 (1994) 1227-1236.
Literature: Fischer, E.H.: Angew. Chem. 105 (1993) 1181-1188 (Nobel Prize Lecture) Walsh, D.A., van Patten. S.M.: FASEB J. 8 (1994) 1227-1236.
Table 17.4-4. Substrates of Proteinkinase C (Examples)
Table 17.4-4. Substrates of Proteinkinase C (Examples)
Table 17.4-3. Substrates of Protein Kinase A (Examples) Figure 17.4-2. Metabolism and Effects of cAMP and Protein Kinase A in Vertebrates
Table 17.4-3. Substrates of Protein Kinase A (Examples) Figure 17.4-2. Metabolism and Effects of cAMP and Protein Kinase A in Vertebrates
Table 17.4-5. Targets Regulated by Binding of Calmodulin-Ca** * Plasma membrine enzyme 1s directly activated ER/SR enzymes via CaM kinase
Table 17.4-5. Targets Regulated by Binding of Calmodulin-Ca** * Plasma membrine enzyme 1s directly activated ER/SR enzymes via CaM kinase
Structure of smooth muscles: The muscle cells are spindle Shaped and mononuclear The filaments do not form myotibrils and are differently (e g , diagonally) arranged Since they contain no troponin other mechanisms regulate the contraction
Structure of smooth muscles: The muscle cells are spindle Shaped and mononuclear The filaments do not form myotibrils and are differently (e g , diagonally) arranged Since they contain no troponin other mechanisms regulate the contraction
Regulation of striated muscle contraction (Figure 17.4-8): Ca** plays a decisive role in muscular contraction After the arrival of neuronal impulses at the neuromuscular endplate (1723) the muscle cell depolarizes This actton potential propagates along the T tubuli (membrane invaginations) to contact sites of the membrane with the sarcoplasmic reticulum (SR) The voltage-sensitive DHP receptors of the cellular membrane transmit the signal to the ryan_ odine receptor Ca** channels of the SR membrane (Fig 17 4-4) Ca** 15 released from this store and increases the cytosolic Ca** concentration greatly
Regulation of striated muscle contraction (Figure 17.4-8): Ca** plays a decisive role in muscular contraction After the arrival of neuronal impulses at the neuromuscular endplate (1723) the muscle cell depolarizes This actton potential propagates along the T tubuli (membrane invaginations) to contact sites of the membrane with the sarcoplasmic reticulum (SR) The voltage-sensitive DHP receptors of the cellular membrane transmit the signal to the ryan_ odine receptor Ca** channels of the SR membrane (Fig 17 4-4) Ca** 15 released from this store and increases the cytosolic Ca** concentration greatly
When the signals for elevation of the cytosolic Ca cease Ca 18 pumped again out of the cvfosol (17 4 4) The decreasing concentration causes dissocia tion of the Ca* /calmodulin/myosin light chain kinase complex and tnactiva tion ot the kinase The myosin light chains are dephosphorylated by myosin light chain phosphatases (e g PPI) Muscle relaxation takes place
When the signals for elevation of the cytosolic Ca cease Ca 18 pumped again out of the cvfosol (17 4 4) The decreasing concentration causes dissocia tion of the Ca* /calmodulin/myosin light chain kinase complex and tnactiva tion ot the kinase The myosin light chains are dephosphorylated by myosin light chain phosphatases (e g PPI) Muscle relaxation takes place
Figure 17 4-12 Absorption Spectra of Rhodopsin (in Rods) and of the Color Receptors (in Cones) Rhodopsin 15 also used in the visual process of mollusks and arthropods Higher plants moyses and algae use the phytochrome system (with a tetra pyrrole chromophore) as light sensor for regulating metabolic processes Photo taxis of bacteria and algae depends on retinal related or flavin sensors
Figure 17 4-12 Absorption Spectra of Rhodopsin (in Rods) and of the Color Receptors (in Cones) Rhodopsin 15 also used in the visual process of mollusks and arthropods Higher plants moyses and algae use the phytochrome system (with a tetra pyrrole chromophore) as light sensor for regulating metabolic processes Photo taxis of bacteria and algae depends on retinal related or flavin sensors
Metarhodopsin II, acting like other serpentine receptors (17 4), activates the heterotrimeric G-protein transducin (G,,®Gg,) The liberated Gy,eGTP binds to the inhibitory y subunit of cGMP phosphodiesterase (PDE) and removes it The PDE 1s now able to hydrolyze cGMP Figure 17 4-10 Structure of Retinal Rods
Metarhodopsin II, acting like other serpentine receptors (17 4), activates the heterotrimeric G-protein transducin (G,,®Gg,) The liberated Gy,eGTP binds to the inhibitory y subunit of cGMP phosphodiesterase (PDE) and removes it The PDE 1s now able to hydrolyze cGMP Figure 17 4-10 Structure of Retinal Rods
‘he series and the index numbers indicate the number of double bonds in the molecule The series | prostanoids are synthesized analogously from 8 11 14 cicosatrienoic cid the series 3 prostanoids from 5 8 11 14 17 etcosapentacnor wid
‘he series and the index numbers indicate the number of double bonds in the molecule The series | prostanoids are synthesized analogously from 8 11 14 cicosatrienoic cid the series 3 prostanoids from 5 8 11 14 17 etcosapentacnor wid
The scrics and the index numbers indicate the numbct of double bonds in the molecule Mcmber of the slow re icting substances of anaphylixis (SRS A) wting ater 10 ' mol/l
The scrics and the index numbers indicate the numbct of double bonds in the molecule Mcmber of the slow re icting substances of anaphylixis (SRS A) wting ater 10 ' mol/l
The cyclooxigenase reaction starts with abstraction of the 13 pro S hydro gen followed by attack of oxygen rearrangements resulting in ring closure and finally reaction of a second oxygen with the resulting radical There exist 2 isoenzymes only one of them 1s inducible The function of the enzyme 1s in hibited by steroidal and nonsteroidal antunflammatory drugs Acetylsalicylic acid (aspirin) acetylates a serine residue in the active center while indometacin phenylbutazone acetaminophen etc compete with the substrate
The cyclooxigenase reaction starts with abstraction of the 13 pro S hydro gen followed by attack of oxygen rearrangements resulting in ring closure and finally reaction of a second oxygen with the resulting radical There exist 2 isoenzymes only one of them 1s inducible The function of the enzyme 1s in hibited by steroidal and nonsteroidal antunflammatory drugs Acetylsalicylic acid (aspirin) acetylates a serine residue in the active center while indometacin phenylbutazone acetaminophen etc compete with the substrate
Table 17.4-7. Series-2 Prostanoids: Prostaglandins, Prostacyclins and Thromboxanes'
Table 17.4-7. Series-2 Prostanoids: Prostaglandins, Prostacyclins and Thromboxanes'
Two examples of receptor tyrosine kinase cascades are presented in detail
Two examples of receptor tyrosine kinase cascades are presented in detail
Table 17.5-1. Vertebrate Receptor Families With Integral Protein-Tyrosine Kinase Activity (RTK). For Structures, see Figure 17.5-1
Table 17.5-1. Vertebrate Receptor Families With Integral Protein-Tyrosine Kinase Activity (RTK). For Structures, see Figure 17.5-1
Figure 17.5-2. EGF Receptor Cascade (Terminology of the human system)
Figure 17.5-2. EGF Receptor Cascade (Terminology of the human system)
Table 17.5-3. ‘Downstream’ Protein Kinases, Counteracting Phosphatases and Transcription Factors
Table 17.5-3. ‘Downstream’ Protein Kinases, Counteracting Phosphatases and Transcription Factors
stream mechanism 15 still unclear This activation apparently can also be performed by RaseGTP Furthermore, RaseGTP can bind to and activate Ral-GRF, which promotes the formation of RaleGTP and, in turn, the activation of phospholipase D This 1n- itlates another sequence of lipid messenger signalling (Fig 17 5-4) Crosstalk with other pathways: Many receptor tyrosine kinases activate the phospholipase Cyl isoenzyme and thus connect with the inositol and the PKC regulated pathways (1743, 1744) Similarly, receptor tyrostne kinases activate the phosphatidylino- sitol 3-kinase (PI 3-K, 17 4 4), which yields mitogenic signals and 15 involved in vesicle trafficking, cell adherence ete The down-
stream mechanism 15 still unclear This activation apparently can also be performed by RaseGTP Furthermore, RaseGTP can bind to and activate Ral-GRF, which promotes the formation of RaleGTP and, in turn, the activation of phospholipase D This 1n- itlates another sequence of lipid messenger signalling (Fig 17 5-4) Crosstalk with other pathways: Many receptor tyrosine kinases activate the phospholipase Cyl isoenzyme and thus connect with the inositol and the PKC regulated pathways (1743, 1744) Similarly, receptor tyrostne kinases activate the phosphatidylino- sitol 3-kinase (PI 3-K, 17 4 4), which yields mitogenic signals and 15 involved in vesicle trafficking, cell adherence ete The down-
b) T and B Cell Receptors. For Structures, see Figure 19 1-9 and 19 1-8
b) T and B Cell Receptors. For Structures, see Figure 19 1-9 and 19 1-8
Protein-tyrosine kinases: a) Receptors, which became phos- phorylated by tyrosine kinases of the Src family are able to bind the adaptor molecule She via its SH2 domain This acts as a linker to the Grb2/Sos protem, which 1s the starting point of the MAPK cascade (17 5 3, compare Fig 17 5-2) Additionally, phosphoryla- tion can provide binding sites for the SH2 domains of phosphati- tylinositol 3 kinase (PI 3-K, 17 44), of hematopoietic cell _phos- phatase (which 1s a negative regulator of cytokine signalling, espe- cially in hematopoietic pathways) and indirectly for PKC (17 4 3) b) After ligand binding and dimerization, the receptors for growth hormone, prolactin, erythropoietin, many interleukins and _inter- ferons associate at membrane-proximal sequences (boxes | and 2) with distinct protein-tyrosine kinases of the Jak family (Jak! 3, Tyk2) The kinases then phosphorylate both the receptor and themselves (Fig 175-5) Thereafter, cytoplasmic STAT proteins (signal transducer and activator of transcription, so far 6 known)
Protein-tyrosine kinases: a) Receptors, which became phos- phorylated by tyrosine kinases of the Src family are able to bind the adaptor molecule She via its SH2 domain This acts as a linker to the Grb2/Sos protem, which 1s the starting point of the MAPK cascade (17 5 3, compare Fig 17 5-2) Additionally, phosphoryla- tion can provide binding sites for the SH2 domains of phosphati- tylinositol 3 kinase (PI 3-K, 17 44), of hematopoietic cell _phos- phatase (which 1s a negative regulator of cytokine signalling, espe- cially in hematopoietic pathways) and indirectly for PKC (17 4 3) b) After ligand binding and dimerization, the receptors for growth hormone, prolactin, erythropoietin, many interleukins and _inter- ferons associate at membrane-proximal sequences (boxes | and 2) with distinct protein-tyrosine kinases of the Jak family (Jak! 3, Tyk2) The kinases then phosphorylate both the receptor and themselves (Fig 175-5) Thereafter, cytoplasmic STAT proteins (signal transducer and activator of transcription, so far 6 known)
Table 17.5-5. Protein-Tyrosine Kinases Associated With Receptors
Table 17.5-5. Protein-Tyrosine Kinases Associated With Receptors
Table 17.5-6. Some Specific Transcription Factors (see also Table 11.4-2 and Figure 11.4-6)
Table 17.5-6. Some Specific Transcription Factors (see also Table 11.4-2 and Figure 11.4-6)
Table 17.6-1. Superfamily of Nuclear Receptors (There are Many Isoforms and Additionally > 40 ‘Orphan’ Receptors With Unknown T igands)
Table 17.6-1. Superfamily of Nuclear Receptors (There are Many Isoforms and Additionally > 40 ‘Orphan’ Receptors With Unknown T igands)
Literature
Literature
§ TM = transmembrane domains tn the individual peptide chain P — P domams essential for pore structure
§ TM = transmembrane domains tn the individual peptide chain P — P domams essential for pore structure
Table 18.1-2. Primary Bulk Transport Mechanisms in Eukarya: ATP Energized Ion Pumps, ATP Synthesis (Selection)
Table 18.1-2. Primary Bulk Transport Mechanisms in Eukarya: ATP Energized Ion Pumps, ATP Synthesis (Selection)
Literature:
Literature:
Table 18.2-3. Properties and Function of Plasma Apolipoproteins
Table 18.2-3. Properties and Function of Plasma Apolipoproteins
Apo (a) 1s omitted in this table It 1s highly homologuous to plasminogen (205) and shows a high variation in its molecular mass (from 250 to > 500 kDa) The heterodimer Apo (a) S S Apo B 1s the protein component of lipoprotein (a) a cholesterol rich particle whose function 1s as yet unknown The concentration of lipoprotein (a) varies considerably from <1 mg/100 ml up to ca 200 mg/100 ml Concentrations of >30 mg/100 ml are considered to be atherogenic (18 2 5)
Apo (a) 1s omitted in this table It 1s highly homologuous to plasminogen (205) and shows a high variation in its molecular mass (from 250 to > 500 kDa) The heterodimer Apo (a) S S Apo B 1s the protein component of lipoprotein (a) a cholesterol rich particle whose function 1s as yet unknown The concentration of lipoprotein (a) varies considerably from <1 mg/100 ml up to ca 200 mg/100 ml Concentrations of >30 mg/100 ml are considered to be atherogenic (18 2 5)
Table 18.2-1. Classification, Properties and Composition of Plasma Lipoproteins (Data vary somewhat between authors) * Migration speed during electrophoresis as compared with o and B globulin
Table 18.2-1. Classification, Properties and Composition of Plasma Lipoproteins (Data vary somewhat between authors) * Migration speed during electrophoresis as compared with o and B globulin
Figure 18 2-1 General Structure of Lipoproteins
Figure 18 2-1 General Structure of Lipoproteins
Figure 18.2-2. Metabolism of Chylomicrons, VLDL and HDL in Mammals
Figure 18.2-2. Metabolism of Chylomicrons, VLDL and HDL in Mammals
18.2.5 Lipid metabolic disorders Some thirty genetic dyslpoproteinemias are known In most cases, also the affected genes and their mutations are well characterized Best known are disturbances in synthesis and function of the LDL receptor, numbered © © in Figure 182-3 They cause familial hypercholesterolemia, a disease with extremely elevated levels of plasma cholesterol which usually leads to premature coronary heart disease
18.2.5 Lipid metabolic disorders Some thirty genetic dyslpoproteinemias are known In most cases, also the affected genes and their mutations are well characterized Best known are disturbances in synthesis and function of the LDL receptor, numbered © © in Figure 182-3 They cause familial hypercholesterolemia, a disease with extremely elevated levels of plasma cholesterol which usually leads to premature coronary heart disease
Table 19.1-1. Components of the Immune Defense Systems
Table 19.1-1. Components of the Immune Defense Systems
Figure 19.1-1. Schematic Diagram of a Lymph Node
Figure 19.1-1. Schematic Diagram of a Lymph Node
called immunoglobulin domains (Figure 19.1-2). Disulfide bonds stabilize the domain structure or connect the polypeptide chains. and transport them as veiled cells via the lymphatic vessels to the regional lymph node, where they settle in the paracortical area.
called immunoglobulin domains (Figure 19.1-2). Disulfide bonds stabilize the domain structure or connect the polypeptide chains. and transport them as veiled cells via the lymphatic vessels to the regional lymph node, where they settle in the paracortical area.
Figure 19.1-6. D-J Gene Recombination by Enzyme-Dependent Looping Out of Intervening DNA
Figure 19.1-6. D-J Gene Recombination by Enzyme-Dependent Looping Out of Intervening DNA
19.1.4 Antigen Recognition by T Lymphocytes
19.1.4 Antigen Recognition by T Lymphocytes
* Ig = immunoglobulin superfamily, NGFR = nerve cell growth factor receptor superfamily, TNF = tumor necrosis factor superfamily
* Ig = immunoglobulin superfamily, NGFR = nerve cell growth factor receptor superfamily, TNF = tumor necrosis factor superfamily
Figure 19.1-9. Membrane Molecules Involved in the Activation of T Lymphocytes
Figure 19.1-9. Membrane Molecules Involved in the Activation of T Lymphocytes
Figure 19.1-17. Regulation of the Antigen-Specific Immune Response
Figure 19.1-17. Regulation of the Antigen-Specific Immune Response
Table 19.2-1. Comparison of Pathway Functions form the membrane-attack_ complex C5b 9 Binding of C6 to C5b enables the binding of C7 This exposes a hydrophobic site on C7 leading to insertion in the lipid bilayer C8 binds to C5b_ 7 on membranes and induces the polymerization of approx 10 to 16 C9 molecules which form a transmembrane ring-shaped structure with a hydrophilic inner channel (about 10 nm diameter) This channel allows free passage of water and other small molecules across the lipid bilayer, leading to cell lysis It resembles the per forin pores generated by cytotoxic T cells and NK cells (19 1 7)
Table 19.2-1. Comparison of Pathway Functions form the membrane-attack_ complex C5b 9 Binding of C6 to C5b enables the binding of C7 This exposes a hydrophobic site on C7 leading to insertion in the lipid bilayer C8 binds to C5b_ 7 on membranes and induces the polymerization of approx 10 to 16 C9 molecules which form a transmembrane ring-shaped structure with a hydrophilic inner channel (about 10 nm diameter) This channel allows free passage of water and other small molecules across the lipid bilayer, leading to cell lysis It resembles the per forin pores generated by cytotoxic T cells and NK cells (19 1 7)
Table 19.2-2. Complement Receptors Table 19.2-3. Complement Control Proteins Induction of inflammation, activation of inflammatory cells: The C5a, C3a and C4a fragments, which are released during the complement activation steps induce directly a local inflammatory reaction, mcluding smooth muscle contraction and increased vas- cular permeability The increase in tissue fluid enhances the move- ment of pathogens to local lymph nodes In addition, CSa (the most active one) acts on mast cells, monocytes and neutrophils and induces a multitude of activating effects
Table 19.2-2. Complement Receptors Table 19.2-3. Complement Control Proteins Induction of inflammation, activation of inflammatory cells: The C5a, C3a and C4a fragments, which are released during the complement activation steps induce directly a local inflammatory reaction, mcluding smooth muscle contraction and increased vas- cular permeability The increase in tissue fluid enhances the move- ment of pathogens to local lymph nodes In addition, CSa (the most active one) acts on mast cells, monocytes and neutrophils and induces a multitude of activating effects
19.2.4 Control Mechanism of the Complement System 17.4.4 Control Mecnanism of the Complement system Inherent amplification mechanisms of the complement system require a tight control in solution and on host cells The activated components are rapidly inactivated unless they bind to a surface * part of the integrin family (19 3)
19.2.4 Control Mechanism of the Complement System 17.4.4 Control Mecnanism of the Complement system Inherent amplification mechanisms of the complement system require a tight control in solution and on host cells The activated components are rapidly inactivated unless they bind to a surface * part of the integrin family (19 3)
Figure 19 2-2 Actions of Complement In addition binding of immune complexes via complement receptors to the surface ot follicular dendritic cells in lymphoid organs results in long lasting antigen deposition for continuous B cell stimulation (19 1 2)
Figure 19 2-2 Actions of Complement In addition binding of immune complexes via complement receptors to the surface ot follicular dendritic cells in lymphoid organs results in long lasting antigen deposition for continuous B cell stimulation (19 1 2)
* The suffixes indicate the types of the subunits, not their numbers
* The suffixes indicate the types of the subunits, not their numbers
Patel, T.P. et ai.. Biochemistry 33 (1994) 14815-14824. Rosen. §.D., Bertozzi, C.R.: Current Opinion in Ceil Biology 6 (1994) 663-673. van der Merwe, P.A., Barclay, A.N., Trends in Biol. Sci. 19 (1994) 354-358. Literature: Carlos, T.M., Harlan, J.M.: Blood 84 (1994) 2068-2101. Lasky, L.A.: Ann. Rev. of Biochem. 64 (1995) 113-139.
Patel, T.P. et ai.. Biochemistry 33 (1994) 14815-14824. Rosen. §.D., Bertozzi, C.R.: Current Opinion in Ceil Biology 6 (1994) 663-673. van der Merwe, P.A., Barclay, A.N., Trends in Biol. Sci. 19 (1994) 354-358. Literature: Carlos, T.M., Harlan, J.M.: Blood 84 (1994) 2068-2101. Lasky, L.A.: Ann. Rev. of Biochem. 64 (1995) 113-139.
* Ratio of activities (k,/Ky values) with and without cofactors (1 5 4) Table 20.3-1. Activity Increase by Coagulation Complex Formation
* Ratio of activities (k,/Ky values) with and without cofactors (1 5 4) Table 20.3-1. Activity Increase by Coagulation Complex Formation
Another :mportant feedback control system of coagulation is in- itiated by thrombin itself: Binding to thrombomodulin (TM, pre- sent at the membrane of intact endothelial cells) converts thrombin into an anticoagulant. It proteolytically activates protein C (PC) to aPC, which in a complex with protein S (PS) inactivates the essen- tial cofactors of the coagulation cascade VUIa and Va as well as their unactivated precursors.
Another :mportant feedback control system of coagulation is in- itiated by thrombin itself: Binding to thrombomodulin (TM, pre- sent at the membrane of intact endothelial cells) converts thrombin into an anticoagulant. It proteolytically activates protein C (PC) to aPC, which in a complex with protein S (PS) inactivates the essen- tial cofactors of the coagulation cascade VUIa and Va as well as their unactivated precursors.
20.4 Platelets (Thrombocytes, Fig. 20.4-1) Platelets play a central part in the hemostatic process When inju- ries to the vessel wall cause a tearing of the endothelial layer, the subendothelial collagen gets exposed Platelets adhere to it
20.4 Platelets (Thrombocytes, Fig. 20.4-1) Platelets play a central part in the hemostatic process When inju- ries to the vessel wall cause a tearing of the endothelial layer, the subendothelial collagen gets exposed Platelets adhere to it
The glycoproteins usually have large extracellular domains These are not shown in detail in Fig 204 | Table 20.4-2, Receptors on the Platelet Membrane
The glycoproteins usually have large extracellular domains These are not shown in detail in Fig 204 | Table 20.4-2, Receptors on the Platelet Membrane
Table 20.5-1. Properties of Fibrinolytic Factors
Table 20.5-1. Properties of Fibrinolytic Factors
Table 26.4-1. Compounds Stored m Vesicles of Thrombocytes
Table 26.4-1. Compounds Stored m Vesicles of Thrombocytes
Fibrinolysis 1s controlled by activation and inhibition processes Specific actrvators convert the inactive proenzyme plasminogen into the active serine protease plasmin, which degrades the fibrin clot (Figure 20 5-1)
Fibrinolysis 1s controlled by activation and inhibition processes Specific actrvators convert the inactive proenzyme plasminogen into the active serine protease plasmin, which degrades the fibrin clot (Figure 20 5-1)
Table 21-1. Selection of Data Banks on Biochemical Topics
Table 21-1. Selection of Data Banks on Biochemical Topics
Contents of the Data Bank ing pathways in animals, plants and bacteria. It provides graphic information on more than 2000 metabolic reactions, including their interrelationships and regulation. The enzymes are linked to ENZYME (7) and SWISS-PROT (11). Details:
Contents of the Data Bank ing pathways in animals, plants and bacteria. It provides graphic information on more than 2000 metabolic reactions, including their interrelationships and regulation. The enzymes are linked to ENZYME (7) and SWISS-PROT (11). Details:

Key takeaways

  • Chains of amino acids form the proteins and peptides.
  • The nucleus contains in addition to the DNA also the nuclear matrix which is composed of the enzymes and factors required for DNA replication DNA repair transcription and processing of the transcription products (111 114) The nucleus is surrounded by a double membrane of lipid bilayers with inte grated proteins Nuclear pores (14 3 2 ca 125 nm diameter) span the nuclear membrane and enable the transport of proteins rRNA etc The inner surface ot the nuclear membrane is covered by nuclear lamina a net of protein fibers which stabilizes the structure and provides attachment points for the chromatin (2 6 4) During cell division the nuclear membrane dissolves 2.2.2 rough ER is also the site of membrane phospholipid synthesis, thus providing membrane material for the departing vesicles (6. 3.2, 13.3.4).
  • However, for most enzymes (as well as for other proteins) the production is regulated:
  • The primary source for the biosynthesis of fatty acids in animals are carbohydrates, followed by a number of amino acids.
  • The overall error rate of translation is ca 1/10000 Consequently, the probability for correct synthesis ot a protein with 300 amino acids is 0 97

Related papers

Biochemistry Metabolism
Digvijay Singh
View PDFchevron_right
Control of catabolic specificity and metabolism
J. Kuo

Biochemical and Biophysical Research Communications, 1965

View PDFchevron_right
Lecture 1: Biochemistry
Con Mèo
View PDFchevron_right
8-25 Intro to Metabolism II & Glycolysis
Khusnul Khotimah

Dr. Popov began this half of the lecture by stating that memorizing structures of coenzymes would be unnecessary. We should instead know what they are used for I. The Structure of Coenzyme A [S30]: a. Coenzyme A is involved in the metabolism of fatty acids II. Enzyme-catalyzed transaminationsp [S31] III. Pridoxal phosphate, the prosthetic group of aminotransferases [S32] IV. Pyridoxal phosphate is bound to the enzyme through a Schiff-base linkage[S33] V. Role of biotin in carboxylation reactions [S34] a. Biotin is a water soluble vitamin. b. Biotin is utilized as a prosthetic group of several enzymes. c. The major function of Biotin is to serve as a cofactor for carboxylation reactions. d. Biotin will later be discussed as being associated with pyruvate carboxylase in the Citric Acid Cycle. e. A carboxylation reaction involves the incorporation of CO2 into a biological molecule.

View PDFchevron_right
An Introduction to Metabolism
magendira mani vinayagam
View PDFchevron_right

Related topics

  • Bioengineering
  • Pharmacology
  • Biochemistry
  • Bioinformatics
  • Genetics
  • Microbiology
  • Biophysics
  • Pharmacy
  • Immunology
  • Molecular Biology
  • Cell Biology