INHIBITION OF PYRUVATE-DEHYDROGENASE AND PYRUVATE-DEHYDROGENASE PHOSPHATE PHOSPHATASE BY GLYOXYLATE

The overall reaction catalyzed by the pyruvate dehydrogenase complex from rat epididymal fat tissue is inhibited by glyoxylate at concentrations greater than 10 .mu.M. The inhibition is competitive with respect to pyruvate; Ki was 80 .mu.M.Qualitatively similar results were observed using pyruvate dehydrogenase from rat liver, kidney and heart. Glyoxylate also inhibits the pyruvate dehydrogenase phosphate phosphatase from rat epididymal fat, with the inhibition being readily detectable using 50 .mu.M glyoxylate. These effects of glyoxylate are largely reversed by mM concentrations of thiols (especially cysteine) because such compounds form relatively stable adducts with glyoxylate. Presumably these inhibitions by low levels of glyoxylate had not been previously observed, because others have used high concentrations of thiols in pyruvate dehydrogenase assays. Since the inhibitory effects are seen with suspected physiological concentrations, it seems likely that glyoxylate partially controls the activity of pyruvate dehydrogenase in vivo.