Prentice Hall c2002Chapter 71 Chapter 7 - Coenzymes and Vitamins Apoenzyme + Cofactor Holoenzyme (protein only)(active) (inactive) Some enzymes require cofactors for activity (1) Essential ions (mostly metal ions) (2) Coenzymes (organic compounds)

Prentice Hall c2002Chapter 72 Fig 7.1 Types of cofactors

Prentice Hall c2002Chapter 73 Many Enzymes Require Coenzymes Coenzymes act as group-transfer reagents Hydrogen, electrons, or other groups can be transferred Larger mobile metabolic groups can be attached at the reactive center of the coenzyme Coenzyme reactions can be organized by their types of substrates and mechanisms Many Enzymes Require Inorganic Cations Enzymes requiring metal ions for full activity: (1) Metal-activated enzymes have an absolute requirement or are stimulated by metal ions (examples: K +, Ca 2+, Mg 2+ ) (2) Metalloenzymes contain firmly bound metal ions at the enzyme active sites (examples: iron, zinc, copper, cobalt )

Prentice Hall c2002Chapter 74 Fig 7.2 Mechanism of carbonic anhydrase Action of carbonic anhydrase, a metalloenzyme Zinc ion promotes the ionization of bound H 2 O. Resulting nucleophilic OH - attacks carbon of CO 2 (continued next slide)

Prentice Hall c2002Chapter 75 Fig. 7.2 (continued)

Prentice Hall c2002Chapter 76 Iron in metalloenzymes Iron undergoes reversible oxidation and reduction: Fe 3+ + e - (reduced substrate) Fe 2+ + (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 c2002Chapter 77 Fig 7.3 Iron-sulfur clusters Iron atoms are complexed with an equal number of sulfide ions (S 2- ) and with thiolate groups of Cys side chains

Reactions of ATP, a metabolite coenzyme ATP is a versatile reactant that can donate its: (1) Phosphoryl group (  -phosphate) (2) Pyrophosphoryl group (  phosphates) (3) Adenylyl group (AMP) (4) Adenosyl group Fig 7.4

SAM synthesis ATP is also a source of other metabolite coenzymes such as S- adenosylmethionine (SAM) SAM donates methyl groups in many biosynthesis reactions Activated methyl group in red Fig 7.5 S-Adenosylmethionine

Prentice Hall c2002Chapter 710 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 c2002Chapter 711 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 and nutritional deficiency diseases

Prentice Hall c2002Chapter 713 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

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

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

Prentice Hall c2002Chapter 716 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 + Catalysis by lactate dehydrogenase

FAD and FMN Flavin adenine dinucleotide (FAD) and Flavin mono-nucleotide (FMN) are derived from riboflavin (Vitamin B 2 ) Flavin coenzymes are involved in oxidation- reduction reactions for many enzymes (flavoenzymes or flavoproteins) FAD and FMN catalyze one or two electron transfers

Fig 7.10 Riboflavin and its coenzymes (a) Riboflavin, (b) FMN (black), FAD (black/blue)

Prentice Hall c2002Chapter 719 Fig 7.11 Reduction, reoxidation of FMN or FAD

Prentice Hall c2002Chapter 720 Coenzyme A (CoA or HS-CoA) Derived from the vitamin pantothenate 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 c2002Chapter 721 Fig 7.12 Coenzyme A

Prentice Hall c2002Chapter 722 Thiamine Pyrophosphate (TPP) TPP is a derivative of thiamine (Vitamin B 1 ) TPP participates in reactions of: (1) Decarboxylation (2) Oxidative decarboxylation Fig 7.14 Thiamine (Vitamin B 1 ) and TPP

Prentice Hall c2002Chapter 723 Pyridoxal Phosphate (PLP) PLP is derived from Vit B 6 family of vitamins Vitamin B 6 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 B 6 Vitamins and pyridoxal phosphate (PLP)

Prentice Hall c2002Chapter 724 Fig 7.18 Mechanism of transaminases

Prentice Hall c2002Chapter 725 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

Prentice Hall c2002Chapter 726 Fig 7.24 Pterin, folate and tetrahydrofolate (THF)

Prentice Hall c2002Chapter 727 Fig 7.27 Abbreviated structure of cobalamin coenzymes

Prentice Hall c2002Chapter 728 Fig 7.28 Intramolecular rearrangements catalyzed by adenosylcobalamin enzymes (a) Rearrangement of an H and substituent X on an adjacent carbon

Fig 7.30 Formation of vitamin A from  -carotene

Prentice Hall c2002Chapter 730 Retinoic acid is a hormone that regulates gene expression in skin

Prentice Hall c2002Chapter 731 Vitamin D A group of related lipids involved in control of Ca 2+ utilization in humans Fig 7.31 Vitamin D 3 and 1,25-dihydroxycholecalciferol

Prentice Hall c2002Chapter 732 Vitamin D deficiency causes rickets

Prentice Hall c2002Chapter 733 Vitamin E (  -tocopherol) A reducing reagent that scavenges oxygen and free radicals May prevent damage to fatty acids in membranes Fig 7.32 Vitamin E (  -tocopherol)

Prentice Hall c2002Chapter 734 Fig 7.32 (a) Structure of vitamin K (b) Vit K-dependent carboxylation

Prentice Hall c2002Chapter 735 Warfarin is an anticoagulant