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Prentice Hall c2002 Chapter 7 1
Chapter 7 Coenzymes and Vitamins
Prentice Hall c2002 Chapter 7 2
Coenzyme, p192-193
• Cofactors: nonprotein components
• Cofactors may be metal ions or organic molecules (coenzyme)
• Cofactor: metal ion + coenzyme
• Prosthetic groups: tightly bound coenzymes
Prentice Hall c2002 Chapter 7 3
Holoenzyme and Apoenzyme
• Holoenzyme– Complex of protein and prosthetic groups
– Catalytically active
• Apoenzyme– The enzyme without the prosthetic groups
– Catalytically inactive
Prentice Hall c2002 Chapter 7 4
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 c2002 Chapter 7 5
Coenzymes, p192-193
• Group-transfer reagents
• Transfer hydrogen, electrons, or other groups
• Reactive center of the coenzyme
Fig 7.1 Types of cofactors, p192
Prentice Hall c2002 Chapter 7 6
7.1 Many Enzymes Require Inorganic Cations, p193
• Enzymes requiring metal ions for full activity:
(1) Metal-activated enzymes
(2) Metalloenzymes
Prentice Hall c2002 Chapter 7 7
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
Prentice Hall c2002 Chapter 7 8
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
Prentice Hall c2002 Chapter 7 9
7.2 Coenzyme Classification, p193-194
(1) Cosubstrates
(2) Prosthetic groups
- Vitamin-derived coenzymes
Prentice Hall c2002 Chapter 7 10
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
Prentice Hall c2002 Chapter 7 11
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
Prentice Hall c2002 Chapter 7 12
Nucleotide-sugar coenzymes are involved in carbohydrate metabolism
• UDP-Glucose is a sugar coenzyme
• Fig 7.6, p197
Prentice Hall c2002 Chapter 7 13
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
Prentice Hall c2002 Chapter 7 14
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
Prentice Hall c2002 Chapter 7 15
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+
Prentice Hall c2002 Chapter 7 16
Reaction of lactate dehydrogenase
Equation 7.3
Fig 7.9 Mechanism of lactate dehydrogenase, p200
Prentice Hall c2002 Chapter 7 17
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
Prentice Hall c2002 Chapter 7 18
Prentice Hall c2002 Chapter 7 19
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
Prentice Hall c2002 Chapter 7 20
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
Prentice Hall c2002 Chapter 7 21
Yeast pyruvate decarboxylase, p203
• Pyruvate acetaldehyde acetyl CoA
TPP
Fig 7.15
Prentice Hall c2002 Chapter 7 22
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
Prentice Hall c2002 Chapter 7 23
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
Prentice Hall c2002 Chapter 7 24
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
Prentice Hall c2002 Chapter 7 25
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)
Prentice Hall c2002 Chapter 7 26
1-71-7
Prentice Hall c2002 Chapter 7 27
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
Prentice Hall c2002 Chapter 7 28
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
Prentice Hall c2002 Chapter 7 29
Methylcobalamin participates in the transfer of methyl groups, p211
• Equation 7.5
Prentice Hall c2002 Chapter 7 30
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
Prentice Hall c2002 Chapter 7 31
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
Prentice Hall c2002 Chapter 7 32
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
Prentice Hall c2002 Chapter 7 33
Fig 13.1 Reactions of the PDH complex, p388
Prentice Hall c2002 Chapter 7 34
7.13 Lipid Vitamins- p212-213
• Vitamin A, D, E, K
• All contain rings and long, aliphatic side chains
• Highly hydrophobic
Prentice Hall c2002 Chapter 7 35
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
Prentice Hall c2002 Chapter 7 36
Prentice Hall c2002 Chapter 7 37
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
Prentice Hall c2002 Chapter 7 38
• 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
Prentice Hall c2002 Chapter 7 39
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)
Prentice Hall c2002 Chapter 7 40
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
Prentice Hall c2002 Chapter 7 41
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
Prentice Hall c2002 Chapter 7 42
Prentice Hall c2002 Chapter 7 43
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
Prentice Hall c2002 Chapter 7 44
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
Prentice Hall c2002 Chapter 7 45
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