DIETARY CONTROL AND TISSUE-SPECIFIC EXPRESSION OF BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE

The branched-chain alpha-ketoacid dehydrogenase complex, catalyst for the rate-limiting step of branched-chain amino acid catabolism, is con trolled by a highly specific protein kinase (branched-chain alpha-keto acid dehydrogenase kinase) that associates tightly with the complex. T he activity state (proportion of the enzyme in its active, dephosphory lated state) of the complex varies dramatically in different rat tissu es. The activity state of the complex in the liver is greater than tha t in any other tissue, and liver contains the lowest amount of kinase protein and kinase mRNA. However, protein malnutrition, a condition un der which the complex is largely phosphorylated and inactive, resulted in a three- to fourfold increase in hepatic kinase activity with an a ccompanying increase in amounts of kinase protein and mRNA, Refeeding a 50% protein diet restored the normal activity state and the original levels of kinase protein and mRNA, The amount of kinase protein assoc iated with the complex rather than changes in specific activity of the kinase appears responsible for observed differences in activity state s of the complex in several rat tissues tested, Accordingly, the level s of kinase protein and mRNA measured are highest in tissues with grea test kinase activity (heart > kidney > liver), correlating reasonably well inversely with activity state of the branched-chain cu-ketoacid d ehydrogenase complex in the respective tissues. These observations sug gest that the amount of kinase protein expressed in various tissues an d in response to dietary protein deficiency is an important factor det ermining the activity state of the complex. (C) 1995 Academic Press, I nc.