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Pyruvate dehydrogenase and 3-fluoropyruvate: chemical competence of 2-acetylthiamin pyrophosphate as an acetyl group donor to dihydrolipoamide

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00368a030· OSTI ID:6764182

The pyruvate dehydrogenase component (E1) of the pyruvate dehydrogenase complex catalyzes the decomposition of 3-fluoropyruvate to CO/sub 2/, fluoride anion, and acetate. Acetylthiamin pyrophosphate (acetyl-TPP) is an intermediate in this reaction. Incubation of the pyruvate dehydrogenase complex with 3-fluoro(1,2-/sup 14/)pyruvate, TPP, coenzyme A (CoASH), and either NADH or pyruvate as reducing systems leads to the formation of (/sup 14/)acetyl-CoA. In this reaction the acetyl group of acetyl-TPP is partitioned by transfer to both CoASH (87 +/- 2%) and water (13 +/- 2%). When the E1 component is incubated with 3-fluoro(1,2-/sup 14/)pyruvate, TPP, and dihydrolipoamide, (/sup 14/)acetyldihydrolipoamide is produced. The formation of (14C)acetyldihydrolipoamide was examined as a function of dihydrolipoamide concentration (0.25-16 mM). A plot of the extent of acetyl group partitioning to dihydrolipoamide as a function of 1/(dihydrolipoamide) showed 95 +/- 2% acetyl group transfer to dihydrolipoamide when dihydrolipoamide concentration was extrapolated to infinity. It is concluded that acetyl-TPP is chemically competent as an intermediate for the pyruvate dehydrogenase complex catalyzed oxidative decarboxylation of pyruvate.

Research Organization:
Institute for Enzyme Research, Madison, WI
OSTI ID:
6764182
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 20; ISSN BICHA
Country of Publication:
United States
Language:
English