Protein expressions of branched-chain keto acid dehydrogenase subunits areselectively and posttranscriptionally altered in liver and skeletal muscleof starved rats

Although it has been well established that starvation increases the oxidati on of branched-chain keto acids (BCKA) in humans and experimental animals s uch as rats, the mechanism has not been adequately investigated. For exampl e, the effects of starvation on protein and mRNA expressions of BCKA dehydr ogenase, which is the key enzyme regulating this oxidation, have not yet be en studied. To initiate such studies, we first determined the activity of B CKA dehydrogenase in the liver and skeletal muscle of fed and starved rats. The levels of activity of BCKA dehydrogenase were significantly greater in tissues of starved rats than in those of fed rats. We then investigated th e possible mechanisms of these increases in enzyme activity. The activity s tate of the enzyme was greater by 3-fold in the muscle of starved compared with fed rats, but there was no significant difference between the activity states in the liver. There were no significant differences between protein expressions of BCKA dehydrogenase subunits (E(1)alpha, E(1)beta and E-2) i n tissues of fed and starved rats; the exceptions were a greater expression of E(1)alpha in the liver and a lower expression of E, p in the skeletal m uscle of starved rats. These differences in protein expressions were not ac companied with any difference in the mRNA expressions of genes encoding E,c r and E,p. The rate of inactivation of BCKA dehydrogenase, mediated by its associated kinase, was significantly slower in the skeletal muscle of starv ed rats but was the same in the liver. However, there was no significant di fference between the protein or the mRNA expressions of the gene encoding B CKA dehydrogenase kinase in tissues of fed and starved rats. These results show that starvation increases the activity of BCKA dehydrogenase in the li ver and skeletal muscle, and the mechanisms of increases in activity are po sttranscriptional and involve cellular rather than the molecular mechanisms .