Mammalian α-Keto Acid Dehydrogenase Complexes

Abstract

Abstract It was found that the pig heart pyruvate dehydrogenase complex is capable of oxidatively decarboxylating α-ketobutyrate at about the rate of 62% of that of pyruvate in the over-all reaction assay and about 79% in the dehydrogenase assay. The complex also shows some activities with α-ketovalerate, α-ketoisocaproate, and α-ketocaproate. These activities were associated with this complex throughout the purification process. The 2-oxoglutarate dehydrogenase complex is highly specific for 2-oxoglutarate, but does also show some activity with α-ketoadipate. The pig heart pyruvate dehydrogenase complex was inhibited competitively by α-ketoisovalerate and α-keto-β-methylvalerate with pyruvate, α-ketobutyrate, and α-ketoisocaproate. The 2-oxoglutarate dehydrogenase complex exhibited mixed inhibition by α-ketoisovalerate, α-keto-β-methylvalerate, and α-ketoisocaproate with 2-oxoglutarate. The significances of the results relative to maple syrup disease are discussed.