The overall objective of the intended research is to elucidate the pathways of amino acid metabolism in skeletal muscle and to investigate their regulation under normal and catabolic conditions such as fasting and diabetes. Specifically, the proposed study has 3 main objectives (a) to extend my current studies on the biochemical mechanisms regulating the catabolism leucine, isoleucine and valine. Skeletal muscle appears to be quantitatively the most important site in the body for these degradative reactions, although little is known of how these pathways are influenced. (b) To investigate the regulation of alanine biosynthesis in muscle and how the glucose-sparing effects of the alanine cycle are achieved. Experimental and clinical evidence suggests that this cycle is important in the maintenance of glucose homeostasis, although the mechanisms remains a mystery. (c) To continue my efforts to identify the precursors of glutamine, and to study the regulation of its synthesis in muscle. To study these problems, methods adapted from my previous studies will be used: 1. specific enzymatic assays to measure metabolite levels. 2. Flux measurements of metabolic pathways in situ using C14-labelled precursors. 3. Measurement of enzyme kinetics in cell-free preparations.