POSTTRANSCRIPTIONAL ALTERATIONS IN PROTEIN MASSES OF HEPATIC BRANCHED-CHAIN KETO ACID DEHYDROGENASE AND ITS ASSOCIATED KINASE IN DIABETES

The key enzyme regulating oxidation of branched-chain keto acids (BCKA s) is BCKA dehydrogenase (BCKAD). We have previously shown that an inc rease in the activity of this enzyme accounts for the increased oxidat ion of leucine in the liver of diabetic rats. In the present experimen t, we have investigated the mechanisms responsible for this increase i n enzyme activity. These studies were performed 96 hours after the wit hdrawal of insulin therapy in rats made diabetic by an injection of st reptozotocin. Diabetes increased the activity state (83% versus 97%, p < .01) as well as the total activity (78 versus 112 nmol/min/mg prote in, p < .01) of BCKAD. The increase in the activity state was due to a 60% fall in the BCKAD kinase activity, which was the result of a 50% decrease in its protein mass. A coordinated increase (50%-70%) in prot ein mass of each BCKAD subunit (E-1 alpha, E-1 beta, and E-2) accounte d for the increase in the total activity of BCKAD, We conclude that di abetes increases the hepatic BCKAD activity by increasing its protein mass and also by decreasing that of its associated kinase. These alter ations appear to occur posttranscriptionally, since diabetes had no ef fect on the gene expressions of BCKAD subunits (E-1 alpha, E-1 beta, a nd E-2) or BCKAD kinase.