OXIDATION OF α-KETO ACIDS

Abstract

Enzyme systems that catalyze the lipoic acid-linked oxidative decarboxylation of pyruvate and α-ketoglutarate have been isolated as multienzyme complexes with molecular weights of several million from bacterial, avian and mammalian cells. These multienzyme complexes have a distinct morphology and catalyze a coordinated sequence of reactions. The Eschcrichia coli pyruvate dehydrogenase complex has been separated into three enzymes-pyruvate dehydrogenase, dihydrolipoyl transacetylase, and a flavoprotein, dihydrolipoyl dehydrogenase. The complex has been reconstituted from the isolated enzymes. The E. coli α-ketoglutarate dehydrogenase complex also has been separated into three enzymes, analogous to those obtaind from the pyruvate dehydrogenase complex and it, too, has been reassembled from the isolated enzymes. The three enzymes are α-ketoglutarate dehydrogenase, dihydrolipoyl transsuccinylase, and dihydrolipoyl dehydrogenase. Pyruvate and α-ketoglutarate dehydrogenase complexes isolated from pig heart muscle and from beef kidney mitochondria appear to be composed of three enzymes, analogous to those comprising the corresponding bacterial complexes. The macromolecular organization of the bacterial and mammalian α-keto acid dehydrogenase complexes has been elucidated to a large extent by correlated biochemical and electron microscopic studies.