5 co-enzymes etc. 20140906
DESCRIPTION
HKU science lecture notesTRANSCRIPT
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Cofactors
• Cofactors are organic or inorganic molecules that are required for the activity of a certain conjugated enzymes
• Apoenzyme (inactive): enzyme without cofactor
• Holoenzyme (active): enzyme with cofactor
• Inorganic cofactors: essential ions
• Organic cofactors: coenzymes
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I. Essential Ion Cofactors
• Metal activated enzymes – require or are stimulated by addition of metal ions - usually monovalent cations (e.g. K+, Na+) and divalent cations (e.g. Mg2+, Zn2+)
• Metal ions of metalloenzymes – cations that are tightly bound to enzyme and participate directly in catalysis – usually transition metals (e.g. Fe, Zn, Cu, Co)
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Metalloenzymes (with bound metal ions at active sites)
Iron sulfur clusters in enzymes involved in oxidation-reduction - Fe complexed with S - Accept or donate electrons
Carbonic anhydrase - A Zn2+ metalloenzyme - CO2 + H2O → bicarbonate
CO2 H2O
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II. Coenzymes
Cosubstrates- - altered in a reaction and dissociated from active site - regenerated to original structure in a subsequent reaction - transfer chemical groups among different enzyme reaction. Prosthetic groups- - remains bound to enzyme - must return to original form Both cosubstrates and prosthetic groups supply reactive groups not
present on the active site amino acid side chains
Vitamin derived coenzymes
• Must be obtained from diet • Synthesized by microorganisms and plants • Vitamin deficiencies lead to disease state • Most vitamins must be enzymatically transformed to function as a
coenzyme
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What about vitamin B4 and B8?
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1. ATP and other nucleotide coenzymes - Supply chemical group to other substrates
A. ATP:
Phosphoryl groups
Nucleotidyl group (AMP)
ATP + substrate
ATP + substrate
ATP + substrate
Substrate–P + ADP
Substrate–PP + AMP
Substrate–AMP + PPi
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B. S-Adenosylmethionine (SAM):
Methyl group
Methionine + ATP SAM
SAM
SAM is a donor of methyl group in biosynthetic reaction
Example:
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C. Nucleotide sugar phosphates - Involved in carbohydrate metabolism - UDP-glucose: carrier of glucose for transfer to other substrate
Formation of UDP-glucose:
Glucosyl group
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2. NAD+ and NADP+
- Nicotinamide coenzymes - Nicotinamide adenine dinucleotide (phosphate) - Precursor – nicotinic acid (Niacin, B3) - Tryptophan can be degraded to niacin - Oxidation-reduction reactions
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3. FAD and FMN
Riboflavin
- Flavin coenzymes - Flavin adenine dinucleotide (FAD); Flavin mononucleotide (FMN) - Precursor – riboflavin (B2) - Prosthetic group - Oxidation-reduction reactions
FAD
= H in FMN
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4. Coenzyme A and acyl carrier protein (ACP) - Transfer of simple carboxylic acids and fatty acids - Free thiol (-SH) group for acyl group attachment
Co-enzyme A
ACP
Vitamin B5
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5. Thiamine Diphosphate (TDP or TPP) - Made from thiamine (B1) - Prosthetic group for enzymes in decarboxylation/carboxylation
- first Vitamin discovered (Vital amine = Vitamin)
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TDP in decarboxylation of pyruvate to acetylaldehyde:
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6. Pyridoxal 5’-phosphate (PLP) - Made from Vitamin B6 - Prosthetic group for enzymes catalyzing reactions involving amino acids
Vitamins of the B6 family
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PLP in transamination reaction
1 1
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7. Biotin - Vitmain B3 - Carboxyl group transfer reaction - ATP-dependent carboxylation - Prosthetic group - Bound to lysine residue in enzyme
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Biotin in ATP-dependent carboxylation of pyruvate
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8. Tetrahydrofolate (THF)
- Folate is converted to THF by the addition of 4 hydrogens to the pterin ring. - Important in transfer of one-carbon units (N10 and N5 are involved) - THF Has a poly-glutamate tail formed by gamma-carboxyl and alpha amino groups (unusual peptide bond).
β α γ β α γ
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One-carbon derivatives of THF:
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9. Cobalamin (B12) coenzymes - B12 is the largest B vitamin - Corrin ring with cobalt cation - Coenzymes: methylcobalamin and adenosylcobalamin
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- Participate in reactions involving intramolecular rearrangements, methyl group transfer, etc.
Cobalamin coenzymes
1. Intramolecular rearrangement:
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2. Methyl group transfer:
5-methylTHF THF
Cobalamin Methylcobalamin
Methionine Homocysteine