Pyruvate Dehydrogenase Complex (PDH Complex)

Overview

Location: Inner mitochondrial membrane
Molecular weight: 9 x 10^6
Function: Converts pyruvate from aerobic glycolysis into acetyl coenzyme A, linking glycolysis to the citric acid cycle
Reaction type: Irreversible oxidative decarboxylation

Enzymes:
- Pyruvate dehydrogenase (with TPP as a coenzyme)
- Dihydrolipoyl transacetylase
- Dihydrolipoyl dehydrogenase
Coenzymes:
- Thiamine pyrophosphate (Vitamin B1)
- FAD (Vitamin B2)
- NAD (Vitamin B3)
- Coenzyme A (Vitamin B5)
- Lipoic acid

Decarboxylation:
- Pyruvate dehydrogenase with TPP decarboxylates pyruvate to hydroxyethyl thiamine pyrophosphate.
Conversion & Transfer:
- Dihydrolipoyl transacetylase converts hydroxyethyl TPP to acetyllipoamide and transfers the acetyl group to CoA, forming acetyl CoA.
Regeneration of Coenzymes:
- Dihydrolipoyl dehydrogenase regenerates oxidized lipoamide by transferring electrons to FAD, forming FADH2.
- FADH2 transfers electrons to NAD+, forming NADH + H+.
ATP Production:
- NADH + H+ enters the respiratory chain, yielding 2.5 ATP.
- Total 5 ATP are produced per PDH cycle from two moles of pyruvate.

End-product inhibition
Phosphorylation state:
- Active as dephosphorylated enzyme
- Inactive as phosphorylated enzyme
Promotors:
- PDH phosphatase (activated by calcium, magnesium, insulin)
- PDH kinase (activated by ATP, NADH, acetyl CoA; inhibited by NAD+, CoA, pyruvate)

Arsenic Poisoning:
- Arsenite inhibits PDH and alpha-ketoglutarate dehydrogenase by binding to lipoic acid's sulfhydryl group.
Lactic Acidosis:
- Caused by PDH deficiency, leading to excess pyruvate converting to lactic acid.

Carbohydrate to Fat Conversion:
- Pyruvate (from carbohydrates) converts to acetyl CoA (mainly from fats)
- Excess carbohydrates can form fats, but fats cannot convert to carbohydrates due to the irreversible nature of PDH reaction, except glycerol and propionic acid which can be converted to glucose.