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Coenzyme
Non-protein component often bound to an enzyme
Usually vitamin-derived
Function in catalysis or carrier
Prosthetic group
Subset of coenzymes tightly bound to enzymes
All prosthetic groups…
Are coenzymes, BUT not all coenzymes are prosthetic groups
Coenzymes in PDH
TPP
Lipoamide
FAD/FADH2
NAD+/NADH
Coenzyme A
NAD+/NADH Vitamin
Niacin (B3)
NAD+/NADH Function
Redox (Resets PDH cycle by oxidizing FADH2 → FAD)
Is NAD+/NADH a prosthetic group?
No, it’s only a coenzyme (not always bound)
FAD/FADH2 Vitamin
Riboflavin (B2)
FAD/FADH2 Function
Redox (Oxidizes lipoamide to reset PDH)
Is FAD/FADH2 a prosthetic group?
YES, it is always bound to E3
Special property of FAD/FADH2
It can be detected in Nickel affinity column (yellow/orange color due to flavin)
TPP Vitamin
Thiamine (B1)
TPP Function
Decarboxylation, its carbon can lose a hydrogen, become negative REACTIVE
Is TPP a prosthetic group?
Yes, it is always bound to E1
Coenzyme A (CoA) Vitamin
Pantothenic acid (B5)
CoA Function
Acyl group transfers (gains acetyl from Lipoamide)
Is CoA a prosthetic group?
No, it is not always bound to an enzyme.
Unique property of CoA
Sulfur, where acyl group attaches
Lipoamide Vitamin
Lipoic acid
Lipoamide Functions
Redox (disulfide bond readily reduced)
Acyl group transfers (reduced sulfhydryl)
Is lipoamide a prosthetic group?
Yes, it’s always attached to E2
PDH Reaction
Glucose (C6) → 2 Pyruvate → 2 Acetyl-CoA + 2CO2
Acetyl-CoA goes to TCA cycle to generate ATP via oxidative phosphorylation.
E1 Coenzyme
TPP
E2 Coenzyme
Lipoamide
E3 coenzyme
FAD/FADH2
PDH Steps
Decarboxylation (E1/TPP)
Reduction and transacetylation (E1/E2 and TPP/LA)
Reposition acetyl group (E2/LA)
Transthiolation (E2/LA and CoA)
Re-oxidation of LA (E2/E3 and LA/FAD)
Re-oxidation of FAD (E3/FAD and NAD)
PDH Complex
Supercomplex of 3 enzymes and their coenzymes
Unique feature of Lipoamide
“Lipoamide arms” and multiple functions
Steps 1-4 of PDH
Form Acetyl-CoA
Steps 5 and 6 of PDH
Reset the cycle by re-oxidation reactions