The proposed research concerns the biochemical mechanisms regulating growth and atrophy of skeletal muscle. These investigations will attempt to clarify the cellular events through which physiological factors, such as the level of muscular work, dietary intake and hormones induce muscle growth or cause muscle atrophy. This work represents a continuation of earlier studies of the regulation of protein degradation, protein synthesis, and amino acid transport in muscle. A major objective of future research will be to learn more about the control, selectivity, and physiological importance of intracellular protein breakdown in muscle and other cells. Despite recent progress, our knowledge of the biochemical mechanisms of intracellular protein breakdown is still rudimentary. We hope to elucidate the pathways for intracellular proteolysis, to identify the responsible degradative enzymes in both mammalian and bacterial cells, and to clarify their modes of regulation. In particular, these studies will concern the role of lysosomal and nonlysosomal enzymes in the degradation of cell proteins and will investigate the very rapid breakdown of abnormal proteins as result from mutations or biosynthetic errors. Related studies will examine the control of amino-acid metabolism in skeletal muscle. Muscle is the major site in the body for degradation of the branched chain amino acids and for the production of alanine and glutamine. We hope to learn more about the physiological significance of these processes and to clarify their relationships to one another to the control of protein turnover in muscle, and to overall energy metabolism in the organism.
