Chapter 7
Coenzymes and Vitamins
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Chapter 7
1
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
(protein only)
Holoenzyme
(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
(2) 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)
• 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:
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7
NAD(P)+
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
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adenosylcobalamin enzymes, p211
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 eamino 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
– 軟骨病
骨質軟化症
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Vitamin D, p213
• Absorbed in the intestine or
photosynthesized in the skin, cholecalciferol
is transported to the liver by vitamin Dbinding protein (DBP, or transcalciferin).
• In the liver, cholecalciferol is 25hydroxylated 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 mixedfunction oxidase hydroxylates 25hydroxyvitamin D to 1, 25-hydroxyvitamin
D3 (Active form)
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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
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D. 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
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p218