The reaction inhibited in thiamine deficiency is
|A||Pyruvate to Acetyl COA|
|B||Citrate to alpha ketoglutarate|
|C||Succinyl CoA to fumarate|
Pyruvate dehydrogenase → A multiple -complex enzyme
a. Pyruvate dehydrogenase is inhibited by its products, Acetyl-CoA and NADH
b. Arsenite or mercuric ions complex the — SH gp of Lipoic acid and inhibit pyruvate dehydrogenase as does
i. dietary deficiency of thiamine (i.e. inhibit pyruvate to Acetyl CoA conversion), Allow pyruvate to
accumulate →leads to lactic acidosis * same things happen in inherited deficiency of pyruvate
c. Active thiamine is thiamine diphosphate (TPP). TPP is a co-enzyme in enzymatic reactions which an activated aldehyde unit is transferred eg.
a. Oxidative decarboxylation: - eg.
i. α-keto acid (α-keto dehydrogenase)
ii. Pyruvate ( Pyruvate dehydrogenase)
iii. α-keto analogs of (Leucine, iso Leucine and valine →α-keto acid decarboxylase
b. (ii) Also required in Tryptophan metabolism by Tryptophan pyrrolase
c. (iii) Transketolase reaction: - in HMP path:
All these reaction are inhibited in thiamine deficiency.