1. Fig 7.2 Mechanism of carbonic anhydrase
Action of carbonic anhydrase, a metalloenzyme
Zinc ion promotes the ionization of bound H2O. Resulting nucleophilic OH- attacks carbon of CO2
Fig 7.2 Mechanism of carbonic anhydrase
Action of carbonic anhydrase, a metalloenzyme
Zinc ion promotes the ionization of bound H2O. Resulting nucleophilic OH- attacks carbon of CO2
(continued next slide)
Prentice Hall c2002
Chapter 7

2. Fig. 7.2 (continued)
Prentice Hall c2002
Chapter 7

3. Iron in metalloenzymes
Iron undergoes reversible oxidation and reduction:
Fe3+ + e- (reduced substrate)
Fe2+ + (oxidized substrate)
Enzyme heme groups and cytochromes contain iron
Nonheme iron exists in iron-sulfur clusters (iron is bound by sulfide ions and S- groups from cysteines)
Iron-sulfur clusters can accept only one e- in a reaction
Iron in metalloenzymes
Iron undergoes reversible oxidation and reduction:
Fe3+ + e- (reduced substrate) 
Fe2+ + (oxidized substrate)
Enzyme heme groups and cytochromes contain iron
Nonheme iron exists in iron-sulfur clusters (iron is bound by sulfide ions and S- groups from cysteines)
Iron-sulfur clusters can accept only one e- in a reaction
Prentice Hall c2002
Chapter 7

4. Fig 7.3 Iron-sulfur clusters
Iron atoms are complexed with an equal number of sulfide ions (S2-) and with thiolate groups of Cys side chains
Fig 7.3 Iron-sulfur clusters
Iron atoms are complexed with an equal number of sulfide ions (S2-) and with thiolate groups of Cys side chains
Prentice Hall c2002
Chapter 7

5. Reactions of ATP, a metabolite coenzyme
ATP is a versatile reactant that can donate its:
(1) Phosphoryl group (g-phosphate)
(2) Pyrophosphoryl group (g,b phosphates)
(3) Adenylyl group (AMP)
(4) Adenosyl group
Reactions of ATP
ATP is a versatile reactant that can donate its:
(1) Phosphoryl group (g-phosphate)
(2) Pyrophosphoryl group (g,b phosphates)
(3) Adenylyl group (AMP)
(4) Adenosyl group
Fig 7.4
Prentice Hall c2002
Chapter 7

6. Fig 7.5 S-Adenosylmethionine
SAM synthesis
ATP is also a source of other metabolite coenzymes such as S-adenosylmethionine (SAM)
SAM donates methyl groups in many biosynthesis reactions
Methionine + ATP S-Adenosylmethionine + Pi + PPi
Fig 7.5 S-Adenosylmethionine
SAM synthesis
ATP is also a source of other metabolite coenzymes such as S-adenosylmethionine (SAM)
SAM donates methyl groups in many biosynthesis reactions
Methionine + ATP  S-Adenosylmethionine + Pi + PPi
Activated methyl group in red
Prentice Hall c2002
Chapter 7

7. S-Adenosylmethionine (SAM) is a methyl donor in many biosynthetic reactions
SAM donates the methyl group for the synthesis of the hormone epinephrine from norepinephrine
S-Adenosylmethionine (SAM) is a methyl donor in many biosynthetic reactions
SAM donates the methyl group for the synthesis of the hormone epinephrine from norepinephrine
Prentice Hall c2002
Chapter 7

8. Vitamin-Derived Coenzymes and Nutrition
Vitamins are required for coenzyme synthesis. Animals must obtain vitamins from diet. (Plants, microorganisms, meat)
Most vitamins are enzymatically transformed to the coenzyme
Table 7.1 Vitamins, nutritional deficiency diseases
Vitamin Disease
Ascorbate (C) Scurvy
Nicotinic acid Pellagra
Riboflavin (B2) Growth retardation
Pantothenate (B3) Dermatitis in chickens
Thiamine (B1) Beriberi
Pyridoxal (B6) Dermatitis in rats
Biotin Dermatitis in humans
Folate Anemia
Cobalamin (B12) Pernicious anemia
Vitamin-Derived Coenzymes and Nutrition
Vitamins are required for coenzyme synthesis and must be obtained from nutrients
Animals rely on plants and microorganisms for vitamin sources (meat supplies vitamins also)
Most vitamins must be enzymatically transformed to the coenzyme
Prentice Hall c2002
Chapter 7

9. Box 7.2 Vitamin C: a vitamin but not a coenzyme
A reducing reagent for hydroxylation of collagen
Deficiency leads to the disease scurvy
Most animals (not primates) can synthesize Vit C
Box 7.2 Vitamin C: a vitamin but not a coenzyme
A reducing reagent for hydroxylation of collagen
Deficiency leads to the disease scurvy
Most animals (not primates) can synthesize Vit C
Prentice Hall c2002
Chapter 7

10. NAD+ and NADP+ Nicotinic acid (niacin) is precursor of NAD+ and NADP+
Lack of niacin causes the disease pellagra
Humans obtain niacin from cereals, meat, legumes
NAD+ and NADP+
Nicotinic acid (niacin) is precursor of NAD+ and NADP+
Lack of niacin causes the disease pellagra
Humans obtain niacin from cereals, meat, legumes
Prentice Hall c2002
Chapter 7

11. Fig 7.8 Oxidized, reduced forms of NAD+ (NADP+)
Prentice Hall c2002
Chapter 7

12. NAD+ and NADP+ are cosubstrates for dehydrogenases
Oxidation by NAD+ and NADP+ occurs two electrons at a time
Dehydrogenases transfer a hydride ion (H:-) from a substrate to pyridine ring C-4 of NAD+ or NADP+
The net reaction is: NAD(P)+ + 2e- + 2H+ NAD(P)H + H+
Fig 7.9 Catalysis by lactate dehydrogenase
NAD+ and NADP+ are cosubstrates for dehydrogenases
Oxidation by pyridine nucleotides always occurs two electrons at a time
Dehydrogenases transfer a hydride ion (H:-) from a substrate to pyridine ring C-4 of NAD+ or NADP+
The net reaction is:
NAD(P)+ + 2e- + 2H+  NAD(P)H + H+
Prentice Hall c2002
Chapter 7

13. FAD and FMN
Flavin adenine dinucleotide (FAD) and Flavin mono-nucleotide (FMN) are derived from riboflavin (Vitamin B2)
Flavin coenzymes are involved in oxidation-reduction reactions for many enzymes (flavoenzymes or flavoproteins)
FAD and FMN catalyze one or two electron transfers
FAD and FMN
Flavin adenine dinucleotide (FAD) and Flavin mono-nucleotide (FMN) are derived from riboflavin (Vitamin B2)
Flavin coenzymes are involved in oxidation-reduction reactions for many enzymes (flavoenzymes or flavoproteins)
FAD and FMN catalyze one or two electron transfers
Prentice Hall c2002
Chapter 7

14. Fig 7.11 Riboflavin and its coenzymes
(a) Riboflavin, (b) FMN (black), FAD (black/blue)
Prentice Hall c2002
Chapter 7

15. Fig 7.12 Reduction, reoxidation of FMN or FAD
Prentice Hall c2002
Chapter 7

16. Coenzyme A (CoA or HS-CoA)
Derived from the vitamin pantothenate (Vit B3)
Participates in acyl-group transfer reactions with carboxylic acids and fatty acids
CoA-dependent reactions include oxidation of fuel molecules and biosynthesis of carboxylic acids and fatty acids
Acyl groups are covalently attached to the -SH of CoA to form thioesters
Coenzyme A (CoA or HS-CoA)
Derived from the vitamin pantothenate (Vit B3)
Participates in acyl-group transfer reactions with carboxylic acids and fatty acids
CoA-dependent reactions include oxidation of fuel molecules and biosynthesis of carboxylic acids and fatty acids
Acyl groups are covalently attached to the -SH of CoA to form thioesters
Prentice Hall c2002
Chapter 7

17. Fig 7.13 (a) Coenzyme A
Prentice Hall c2002
Chapter 7

18. Thiamine Pyrophosphate (TPP)
TPP is a derivative of thiamine (Vitamin B1)
TPP participates in reactions of: (1) Decarboxylation (2) Oxidative decarboxylation
Fig Thiamine (Vitamin B1) and TPP
Thiamine Pyrophosphate (TPP)
TPP is a derivative of thiamine (Vitamin B1)
TPP participates in reactions of: (1) Decarboxylation (2) Oxidative decarboxylation (3) Transketolase enzyme reactions
Prentice Hall c2002
Chapter 7

19. Pyridoxal Phosphate (PLP)
PLP is derived from Vit B6 family of vitamins
Vitamin B6 is phosphorylated to form PLP
PLP is a prosthetic group for enzymes catalyzing reactions involving amino acid metabolism (isomerizations, decarboxylations, side chain eliminations or replacements)
Fig B6 Vitamins and pyridoxal phosphate (PLP)
Pyridoxal Phosphate (PLP)
PLP is derived from Vit B6 family of vitamins (deficiencies lead to dermatitis and disorders of protein metabolism)
Vitamin B6 is phosphorylated to form PLP
PLP is a prosthetic group for enzymes catalyzing reactions involving amino acid metabolism (isomerizations, decarboxylations, side chain eliminations or replacements)
Prentice Hall c2002
Chapter 7

20. Fig 7.18 Mechanism of transaminases
Prentice Hall c2002
Chapter 7

21. Biotin (Why you shouldn’t eat raw eggs!)
Biotin is required in very small amounts because it is available from intestinal bacteria. Avidin (egg protein) binds biotin very tightly and may lead to a biotin deficiency (cooking eggs denatures avidin so it does not bind biotin)
Enzymes using biotin as a prosthetic group catalyze :
(1) Carboxyl-group transfer reactions
(2) ATP-dependent carboxylation reactions
Biotin (Why you shouldn’t eat raw eggs!)
Biotin is required in very small amounts because it is available from intestinal bacteria
Avidin (raw egg protein) binds biotin very tightly and may lead to a biotin deficiency (cooking eggs denatures avidin so it does not bind biotin)
Biotin (a prosthetic group) enzymes catalyze:
(1) Carboxyl-group transfer reactions
(2) ATP-dependent carboxylation reactions
Prentice Hall c2002
Chapter 7

22. Fig 7.21 Pterin, folate and tetrahydrofolate (THF)
Prentice Hall c2002
Chapter 7

23. Fig 7.24 Abbreviated structure of cobalamin coenzymes
Prentice Hall c2002
Chapter 7

24. Fig 7.25 Intramolecular rearrangements catalyzed by adenosylcobalamin enzymes
(a) Rearrangement of an H and substituent X on an adjacent carbon
Prentice Hall c2002
Chapter 7

25. Fig 7.27 Formation of vitamin A from b-carotene
Prentice Hall c2002
Chapter 7

26. Retinoic acid is a hormone that regulates gene expression in skin
Prentice Hall c2002
Chapter 7

27. Vitamin D
A group of related lipids involved in control of Ca2+ utilization in humans
Fig Vitamin D3 and 1,25-dihydroxycholecalciferol
Vitamin D
A group of related lipids involved in control of Ca2+ utilization in humans
Fig Vitamin D3 and 1,25-dihydroxycholecalciferol
Prentice Hall c2002
Chapter 7

28. Vitamin D deficiency causes rickets
Prentice Hall c2002
Chapter 7

29. Vitamin E (a-tocopherol)
A reducing reagent that scavenges oxygen and free radicals
May prevent damage to fatty acids in membranes
Fig Vitamin E (a-tocopherol)
Vitamin E (a-tocopherol)
A reducing reagent that scavenges oxygen and free radicals
May prevent damage to fatty acids in membranes
Fig Vitamin E (a-tocopherol)
Prentice Hall c2002
Chapter 7

30. Fig 7.30 (a) Structure of vitamin K (b) Vit K-dependent carboxylation
Prentice Hall c2002
Chapter 7

31. Warfarin is an anticoagulant
Prentice Hall c2002
Chapter 7