The overall objectives of this project are to identify and examine the regulatory steps involved in the control of protein turnover and amino acid metabolism in skeletal muscle with respect to: a) the effects of hormone deprivation and replacement in vivo; b) the modulation by insulin, glucocorticoids, growth hormone, thyroxine, and certain other hormonal interactions in vitro; and c) the influence of diet, substrate availability, and contractile activity. We are also attempting to determine the influence of these factors on the turnover of ribosomal RNA, investigate the mechanisms of intracellular protein degradation, and further characterize the reactions involved in peptide initiation. The studies employ the perfused rat hemicorpus as the principal experimental model. This preparation consists predominantly of skeletal muscle and remains in excellent physiological condition during perfusion. The preparation is used to localize the effects of hormones, substrates, and other factors to specific steps in the pathway of protein synthesis, i.e. amino acid transport, amino acid activation, peptide initiation, and peptide elongation. Effects of the various conditions on rates of protein degradation are determined in the perfused hemicorpus and related to the activities of various lysosomal and non-lysosomal proteases in skeletal muscle. The perfused hemicorpus also permits studies of the biochemical mechanisms underlying alanine and glutamine production and branched-chain amino acid oxidation in skeletal muscle.
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