Answer to Question #85993 in Biochemistry for Kanika Kapoor

Question

How is the enzyme pyruvate dehydrogenase complex different from other enzymes? Explain how it functions in the conversion of pyruvate to acetyl-CoA.

Answer 1

Pyruvate dehydrogenase complex is a multienzyme complex containing multiple copies of 3 enzymes (E1 = pyruvate dehydrogenase, E2 = dihydrolipoamide acetyltransferase, E3 = dihydrolipoamide dehydrogenase). These three catalytic components work sequentially, catalyzing the oxidative decarboxylation of pyruvate with the formation of acetyl-CoA, CO2 and NADH (H+). The E1 is a thiamin pyrophosphate (TPP)-dependent enzyme and catalyzes two consecutive steps : 1). the decarboxylation of pyruvate to CO2 with the formation of C2α-hydroxyethylidene-TPP (enamine) intermediate and 2). the reductive acetylation of the lipoyl groups covalently attached to the E2. The E2 catalyzes the transfer of an acetyl moiety to CoA to form acetyl-CoA . The transfer of electrons from the dihydrolipoyl moieties of E2 to FAD and then to NAD+ is carried out by E3. 

Overall reaction: pyruvate + CoASH + NAD+ → acetyl-CoA + CO2 + NADH + H+

Patel, Mulchand S et al. “The pyruvate dehydrogenase complexes: structure-based function and regulation” Journal of biological chemistry vol. 289,24 (2014): 16615-23.