The effects of the nutritional state, muscular activity, substrates, hormones and hormone deficiencies, particularly diabetes mellitus, on amino acid metabolism, will be investigated in rats. The effect of some of the above factors, particularly that of the branched chain amino acids (bcaa) on protein turnover in muscles and the regulation of the branched chain alpha-keto acid (bcka) dehydrogenase system at the cellular level, will be studied. The latter system is rate limiting for bcaa catabolism in several tissues including muscles. We previously reported that 1) bcaa oxidation by muscles is stimulated in protein catabolic states e.g., fasting and diabetes, 2) bcaa particularly leucine play a regulatory role in muscle protein turnover which entails stimulation of protein synthesis and inhibition of proteolysis. The former effect appears to involve peptide chain initiation, is synergistic with that of insulin and may be required for the anabolic effect of insulin after a prolonged fast. The mechanism of the diabetes induced stimulation of bcaa oxidation will be studied in isolated muscles and cell free muscle preparations. Studies will be continued concerning the regulation of the hepatic branched chain alpha-keto acid dehydrogenase system, the role of hormones, ions (particularly Ca ions, co-factors and nucleotides, in cell free preparations. Purification of the mitochondrial enzyme complex will be attempted and regulation studied. Studies concerning the effect of diabetes, insulin, hormones, the nutritional state and the availability of certain amino acids and fuels on protein turnover in muscles will be continued.