Chapter 7 Coenzymes and Vitamins

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Chapter 7 Coenzymes and Vitamins
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Coenzyme, p192-193

• Cofactors nonprotein components
• Cofactors may be metal ions or organic molecules
  (coenzyme)
• Cofactor metal ion coenzyme
• Prosthetic groups tightly bound coenzymes

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Holoenzyme and Apoenzyme

• Holoenzyme
• Complex of protein and prosthetic groups
• Catalytically active
• Apoenzyme
• The enzyme without the prosthetic groups
• Catalytically inactive

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• Some enzymes require cofactors for activity
• (1) Essential ions (mostly metal ions)
• (2) Coenzymes (organic compounds)

Apoenzyme Cofactor Holoenzyme (protein
only) (active) (inactive)
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Coenzymes, p192-193

• Group-transfer reagents
• Transfer hydrogen, electrons, or other groups
• Reactive center of the coenzyme

Fig 7.1 Types of cofactors, p192
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7.1 Many Enzymes Require Inorganic Cations, p193

• Enzymes requiring metal ions for full activity
• (1) Metal-activated enzymes
• (2) Metalloenzymes

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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

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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

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7.2 Coenzyme Classification, p193-194

• (1) Cosubstrates
• Prosthetic groups
• - Vitamin-derived coenzymes

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7.3 ATP and other nucleotidecosubstrate, p196

• Nucleoside triphosphates act as cosubstrate
• Fig 7.4 ATP
• Donate
• (1) Phosphoryl group (g-phosphate)
• (2) Pyrophosphoryl group (g, b-phosphates)
• (3) Adenylyl group (AMP)
• (4) Adenosyl group

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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

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Nucleotide-sugar coenzymes are involved in
carbohydrate metabolism

• UDP-Glucose is a sugar coenzyme
• Fig 7.6, p197

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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

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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

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7.4 NAD and NADP, p197

• Vitamin Nicotinic acid (niacin)
• CoenzymeNAD 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

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Reaction of lactate dehydrogenase
Equation 7.3 Fig 7.9 Mechanism of lactate
dehydrogenase, p200
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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

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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

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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

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Yeast pyruvate decarboxylase, p203

• Pyruvate ? acetaldehyde ? acetyl CoA
• TPP
• Fig 7.15

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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

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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

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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

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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)

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1-7
1-7
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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

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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

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Methylcobalamin participates in the transfer of
methyl groups, p211

• Equation 7.5

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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

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Fig 7.26 Lipoamide, p212

• Lipoic acid is bound via an amide linkage to the
  e-amino group of an enzyme lysine
• Transfer of an acyl group between active sites
• - Equation 7.6

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Pyruvate dehydrogenase complex p385-386

• 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

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Fig 13.1 Reactions of the PDH complex, p388
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7.13 Lipid Vitamins- p212-213

• Vitamin A, D, E, K
• All contain rings and long, aliphatic side chains
• Highly hydrophobic

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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

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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
• ??? ?????

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Vitamin D, p213

• 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

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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)

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C. Vitamin E (a-tocopherol), p213

• A reducing reagent that scavenges oxygen and free
  radicals
• May prevent damage to fatty acids in membranes
• Fig 7.29

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Vitamin K (phylloquinone), p214 Fig 7.29

• Required for synthesis of blood coagulation
  proteins
• A coenzyme for mammalian carboxylases that
  convert glutamate to g-carboxyglutamate
• Equation 7.7 Vit K-dependent carboxylation, p214
• Calcium binds to the g-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

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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

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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

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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