Inhibition of glycine oxidation by pyruvate, α-ketoglutarate, and branched-chain α-keto acids in rat liver mitochondria: Presence of interaction between the glycine cleavage system and α-keto acid dehydrogenase complexes

Abstract

Pyruvate, α-ketoglutarate, and branched-chain α-keto acids which were transaminated products of valine, leucine, and isoleucine inhibited glycine decarboxylation by rat liver mitochondria. However, glycine synthesis (the reverse reaction of glycine decarboxylation) was stimulated by those α-keto acids with the concomitant decarboxylation of α-keto acid added in the absence of NADH. Both the decarboxylation and the synthesis of glycine by mitochondrial extract were affected similarly by α-ketoglutarate and branched-chain α-keto acids in the absence of pyridine nucleotide, but not by pyruvate. This failure of pyruvate to have an effect was due to the lack of pyruvate oxidation activity in the mitochondrial extract employed. It indicated that those α-keto acids exerted their effects by providing reducing equivalents to the glycine cleavage system, possibly through lipoamide dehydrogenase, a component shared by the glycine cleavage system and α-keto acid dehydrogenase complexes. On the decarboxylation of pyruvate, α-ketoglutarate, and branched-chain α-keto acids in intact mitochondria, those α-keto acids inhibited one another. In similar experiments with mitochondrial extract, decarboxylations of α-ketoglutarate and branched-chain α-keto acid were inhibited by branched-chain α-keto acid and α-ketoglutarate, respectively, but not by pyruvate. NADH was unlikely to account for the inhibition. We suggest that the lipoamide dehydrogenase component is an indistinguishable constituent among α-keto acid dehydrogenase complexes and the glycine cleavage system in mitochondria in nature, and that lipoamide dehydrogenase-mediated transfer of reducing equivalents might regulate α-keto acid oxidation as well as glycine oxidation.