Chapter 7 1Prentice Hall c2002

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)

Chapter 7 2Prentice Hall c2002

Fig. 7.2 (continued)

Chapter 7 3Prentice Hall c2002

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

Chapter 7 4Prentice Hall c2002

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

Chapter 7 5Prentice Hall c2002

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

Fig 7.4

Chapter 7 6Prentice Hall c2002

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

Fig 7.5 S-Adenosylmethionine

Chapter 7 7Prentice Hall c2002

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

Chapter 7 8Prentice Hall c2002

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 DiseaseAscorbate (C) ScurvyNicotinic acid Pellagra

Riboflavin (B2) Growth retardation

Pantothenate (B3) Dermatitis in chickens

Thiamine (B1) Beriberi

Pyridoxal (B6) Dermatitis in ratsBiotin Dermatitis in humansFolate Anemia

Cobalamin (B12) Pernicious anemia

Chapter 7 9Prentice Hall c2002

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

Chapter 7 10Prentice Hall c2002

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

Chapter 7 11Prentice Hall c2002

Fig 7.8 Oxidized, reduced forms of NAD+ (NADP+)

Chapter 7 12Prentice Hall c2002

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

Chapter 7 13Prentice Hall c2002

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

Chapter 7 14Prentice Hall c2002

Fig 7.11 Riboflavin and its coenzymes

(a) Riboflavin, (b) FMN (black), FAD (black/blue)

Chapter 7 15Prentice Hall c2002

Fig 7.12 Reduction, reoxidation of FMN or FAD

Chapter 7 16Prentice Hall c2002

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

Chapter 7 17Prentice Hall c2002

Fig 7.13 (a) Coenzyme A

Chapter 7 18Prentice Hall c2002

Thiamine Pyrophosphate (TPP)

• TPP is a derivative of thiamine (Vitamin B1)

• TPP participates in reactions of: (1) Decarboxylation(2) Oxidative decarboxylation

Fig 7.14 Thiamine (Vitamin B1) and TPP

Chapter 7 19Prentice Hall c2002

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 7.16 B6 Vitamins and pyridoxal

phosphate (PLP)

Chapter 7 20Prentice Hall c2002

Fig 7.18 Mechanism of transaminases

Chapter 7 21Prentice Hall c2002

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

Chapter 7 22Prentice Hall c2002

Fig 7.21 Pterin, folate and tetrahydrofolate (THF)

Chapter 7 23Prentice Hall c2002

Fig 7.24

Abbreviated structure of cobalamin coenzymes

Chapter 7 24Prentice Hall c2002

Fig 7.25 Intramolecular rearrangements catalyzed by adenosylcobalamin enzymes

(a) Rearrangement of an H and substituent X on an adjacent carbon

Chapter 7 25Prentice Hall c2002

Fig 7.27 Formation of vitamin A from b-carotene

Chapter 7 26Prentice Hall c2002

Retinoic acid is a hormone that regulates gene expression in skin

Chapter 7 27Prentice Hall c2002

Vitamin D

• A group of related lipids involved in control of Ca2+ utilization in humans

• Fig 7.28 Vitamin D3 and 1,25-dihydroxycholecalciferol

Chapter 7 28Prentice Hall c2002

Vitamin D deficiency causes rickets

Chapter 7 29Prentice Hall c2002

Vitamin E (a-tocopherol)

• A reducing reagent that scavenges oxygen and free radicals

• May prevent damage to fatty acids in membranes

Fig 7.29 Vitamin E (a-tocopherol)

Chapter 7 30Prentice Hall c2002

Fig 7.30 (a) Structure of vitamin K (b) Vit K-dependent carboxylation

Chapter 7 31Prentice Hall c2002

Warfarin is an anticoagulant