Alcoholics may develop fatal lactic acidosis due to inhibition of which of the following enzyme?: (A) Pyruvate dehydrogenase, (B) Dihydrolipoyl transacetylase, (C) Dihydrolipoyl dehydrogenase, (D) Phosphoglycerate kinase
Answer is A. Pyruvate is decarboxylated by the pyruvate dehydrogenase component of the enzyme complex to a hydroxyethyl derivative of the thiazole ring of enzyme-bound thiamin diphosphate. Arsenite and mercuric ions react with the 'SH groups of lipoic acid and inhibit pyruvate dehydrogenase, as does a dietary deficiency of thiamin allowingpyruvate to accumulate. Many alcoholics are thiamin deficient (both because of a poor diet and also because alcohol inhibits thiamin absorption), and may develop potentially fatal pyruvic and lactic acidosis.Ref: Harper&;s Biochemistry; 30th edition; Chapter 17; Glycolysis & the Oxidation of Pyruvate