Prentice Hall c2002Chapter 71 Chapter 7 Coenzymes and Vitamins

Prentice Hall c2002 Chapter 7 1

Chapter 7 Coenzymes and Vitamins


Coenzyme, p192-193

• Cofactors: nonprotein components

• Cofactors may be metal ions or organic molecules (coenzyme)

• Cofactor: metal ion + coenzyme

• Prosthetic groups: tightly bound coenzymes


Holoenzyme and Apoenzyme

• Holoenzyme– Complex of protein and prosthetic groups

– Catalytically active

• Apoenzyme– The enzyme without the prosthetic groups

– Catalytically inactive


Apoenzyme + Cofactor Holoenzyme

(protein only) (active)

(inactive)

• Some enzymes require cofactors for activity

(1) Essential ions (mostly metal ions)

(2) Coenzymes (organic compounds)


Coenzymes, p192-193

• Group-transfer reagents

• Transfer hydrogen, electrons, or other groups

• Reactive center of the coenzyme

Fig 7.1 Types of cofactors, p192


7.1 Many Enzymes Require Inorganic Cations, p193

• Enzymes requiring metal ions for full activity:

(1) Metal-activated enzymes

(2) Metalloenzymes


Fig 7.2 Mechanism of carbonic anhydrase, p193

• A metalloenzyme

• Zinc ion promotes the ionization of bound H2O. Resulting nucleophilic OH- attacks carbon of CO2


Iron in metalloenzymes, p193

Fe3+ + e- (reduced substrate)

Fe2+ + (oxidized substrate)

• Heme groups, heme protein

• Cytochromes contain iron

• Nonheme iron: iron-sulfur clusters

• Iron-sulfur clusters can accept only one e- in a reaction


7.2 Coenzyme Classification, p193-194

(1) Cosubstrates

(2) Prosthetic groups

- Vitamin-derived coenzymes


7.3 ATP and other nucleotidecosubstrate, p196

• Nucleoside triphosphates act as cosubstrate

Fig 7.4 ATP Donate(1) Phosphoryl group (-phosphate) (2) Pyrophosphoryl group (, -phosphates) (3) Adenylyl group (AMP) (4) Adenosyl group


S-adenosylmethionine synthesis, p196

• ATP is also a source of other metabolite coenzymes such as S-adenosylmethionine

• Equation 7.1

• S-adenosylmethionine donates methyl groups in many biosynthesis reactions

– Synthesis of the hormone epinephrine from norepinephrine

– Equation 7.2


Nucleotide-sugar coenzymes are involved in carbohydrate metabolism

• UDP-Glucose is a sugar coenzyme

• Fig 7.6, p197


Vitamin-Derived Coenzymes and Nutrition, p194

• Animals rely on plants and microorganisms for vitamin sources (meat supplies vitamins also)

• Most vitamins must be enzymatically transformed to the coenzyme

• Table 7.1 Vitamins, nutritional deficiency diseases, p194


Box 7.1 Vitamin C: a vitamin but not a coenzyme, p195

• A reducing reagent for hydroxylation of collagen

• Deficiency leads to the disease scurvy

• Most animals (not primates) can synthesize Vit C

• Anti-oxidant


7.4 NAD+ and NADP+, p197

• Vitamin: Nicotinic acid (niacin)

• Coenzyme:NAD+ and NADP+

• Lack of niacin causes the disease pellagra

• Humans obtain niacin from cereals, meat, legumes

• Fig 7.8

• Dehydrogenases transfer a hydride ion (H:-, one proton and two electrons) from a substrate to pyridine ring C-4 of NAD+ or NADP+

• The net reaction is: NAD(P)+ + 2e- + 2H+ NAD(P)H + H+


Reaction of lactate dehydrogenase

Equation 7.3

Fig 7.9 Mechanism of lactate dehydrogenase, p200


7.5 FAD and FMN, p200-201

• Flavin adenine dinucleotide (FAD)

• Flavin mono-nucleotide (FMN)

• Derived from riboflavin (Vit B2)

• In oxidation-reduction reactions

• One or two electron transfers

• Fig 7.10, Fig 7.11



7.6 Coenzyme A (CoA or HS-CoA)p201-202

• Derived from the vitamin pantothenate (Vit B3)

• Acyl-group transfer reactions

• Acyl groups are covalently attached to the -SH of CoA to form thioesters

• Fig 7.12, Fig. 7.13


7.7 Thiamine Pyrophosphate (TPP)p202-203

• TPP is a derivative of thiamine (Vit B1)

• Reactive center: thiazolium ring

• Fig 7.14

• TPP participates in reactions of: (1) Decarboxylation(2) Oxidative decarboxylation of -keto acids(3) Transketolase enzyme reactions


Yeast pyruvate decarboxylase, p203

• Pyruvate acetaldehyde acetyl CoA

TPP

Fig 7.15


7.8 Pyridoxal Phosphate (PLP), p203-206

• Derived from Vit B6

• Vitamin B6 (Pyridoxine) is phosphorylated to form PLP

• Involving amino acid metabolism (isomerizations, decarboxylations, side chain eliminations or replacements)

• The reactive center is the aldehyde group

• Fig 7.16, Fig 7.17

• Fig 7.18 TPP in transaminase action


7.9 Biotin, p207

• 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


Fig 7.19 Enzyme-bound biotin, p207

• Biotin is linked by an amide bond to the e-amino group of a lysine residue of the enzyme

• The reactive center of biotin is the N-1

• Fig 7.20 Reaction catalyzed by pyruvate carboxylase, p207


7.10 Tetrahydrofolate (THF)p208, Fig 7.21, 7.22

• From vitamin folate: in green leaves, liver, yeast

• The coenzyme THF is a folate derivative where positions 5,6,7,8 of the pterin ring are reduced (Equation 7.4).

• THF contains 5-6 glutamate residues which facilitate binding of the coenzyme to enzymes

• Transfers of one carbon units at the oxidation levels of methanol (CH3OH), formaldehyde (HCHO), formic acid (HCOOH)


1-71-7


Fig. 7.23 5,6,7,8, Tetrahydrobiopterin, a pterin coenzyme, p210

• Coenzyme has a 3-carbon side chain at C-6

• Not vitamin-derived, but synthesized by some organisms


7.11 Cobalamin (Vitamin B12), p210-211

• Coenzymes: methylcobalamin, adenosylcobalamin

• Cobalamin contains a corrin ring system and a cobalt (it is synthesized by only a few microorganisms)

• Humans obtain cobalamin from foods of animal origin (deficiency leads to pernicious anemia)

• Coenzymes participate in enzyme-catalyzed molecular rearrangements

• Fig. 7.24

• Fig 7.25 Intramolecular rearrangements catalyzed by adenosylcobalamin enzymes, p211


Methylcobalamin participates in the transfer of methyl groups, p211

• Equation 7.5


7.12 Lipoamide, p212

• From lipoic acid

• Coenzyme: lipoamide

• Animals can synthesize lipoic acid, it is not a vitamin

• Lipoic acid is an 8-carbon carboxylic acid with sulfhydryl groups on C-6 and C-8

• Lipoamide functions as a “swinging arm” that carries acyl groups between active sites in multienzyme complexes


Fig 7.26 Lipoamide, p212

• Lipoic acid is bound via an amide linkage to the -amino group of an enzyme lysine

• Transfer of an acyl group between active sites

- Equation 7.6


Pyruvate dehydrogenase complexp385-386

• Equation 13.1• Conversion of pyruvate to acetyl CoA• Pyruvate dehydrogenase complex (PDH complex)

is a multienzyme complex containing:• 3 enzymes + 5 coenzymes + other proteins

(+ ATP coenzyme as a regulator)• E1 = pyruvate dehydrogenase• E2 = dihydrolipoamide acetyltransferase• E3 = dihydrolipoamide dehydrogenase


Fig 13.1 Reactions of the PDH complex, p388


7.13 Lipid Vitamins- p212-213

• Vitamin A, D, E, K

• All contain rings and long, aliphatic side chains

• Highly hydrophobic


A. Vitamin A (Retinol), p213

• Vit A exists in 3 forms: alcohol (retinol), aldehyde and retinoic acid

• Retinol and retinoic acid are signal compounds

• Rentinal (aldehyde) is a light-sensitive compound with a role in vision

• Fig 7.27



B. Vitamin D, p213, Fig 7.28

• Control of Ca2+ utilization in humans• Regulates intestinal absorption of calcium and its

deposition in bones.

• Active form: 1, 25-hydroxyvitamin D3

• Under the sunlight, vitamin D3 (cholecalciferol) is formed nonenzymatically in the skin from the steroid 7-dehydrocholesterol.

• Vitamin D deficiency– Ricket in children, osteomalacia in adults

– 軟骨病骨質軟化症


• Absorbed in the intestine or photosynthesized in the skin, cholecalciferol is transported to the liver by vitamin D-binding protein (DBP, or transcalciferin).

• In the liver, cholecalciferol is 25-hydroxylated by mixed-function oxidase to form 25-hydroxyvitamin D3

Vitamin D, p213


Vitamin D, p213

• 25-hydroxyvitamin D is the mayor circulating form of vitamin D in the body, but the biological activity is far less than the final active form, 1, 25-hydroxyvitamin D3

• In the kidney, a mitochondrial mixed-function oxidase hydroxylates 25-hydroxyvitamin D to 1, 25-hydroxyvitamin D3 (Active form)


C. Vitamin E (-tocopherol), p213

• A reducing reagent that scavenges oxygen and free radicals

• May prevent damage to fatty acids in membranes

Fig 7.29


D. Vitamin K (phylloquinone), p214 Fig 7.29

• Required for synthesis of blood coagulation proteins

• A coenzyme for mammalian carboxylases that convert glutamate to -carboxyglutamate

• Equation 7.7 Vit K-dependent carboxylation, p214

• Calcium binds to the -carboxyGlu residues of these coagulation proteins which adhere to platelet surfaces

• Vitamin K analogs (used as competitive inhibitors to prevent regeneration of dihydrovitamin K) are given to individuals who suffer excessive blood clotting



7.14 Ubiquinone (Coenzyme Q), p214

• Electrons transfer

• Plastoquinone (ubiquinone analog) functions in photosynthetic electron transport

• Hydrophobic tail: repeat of five-carbon isoprenoid units

• Fig 7.30, p215

• Fig 7.31, p215


7.15 Protein Coenzymes , p215

• Protein coenzymes (group-transfer proteins)

• Participate in:(1) Group-transfer reactions (2) Oxidation-reduction reactions: transfer a hydrogen or

an electron

• Metal ions, iron-sulfur clusters and heme groups are commonly found in these proteins

• Fig 7.32 Thioredoxin, p216


7.16 Cytochromes, p216

• Heme-containing coenzymes

• Fe(III) undergoes reversible one-electron reduction

• Cytochromes a,b and c have different visible absorption spectra and heme prosthetic groups

• Electron transfer potential varies among different cytochromes due to the different protein environment of each prosthetic group

• Fig 7.33 Heme group of cyt a,b, and c p217

• Fig 7.34 Absorption spectra of oxidized and reduced cytochrome c, p218

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Prentice Hall c2002Chapter 71 Chapter 7 Coenzymes and Vitamins