Nutritional and hormonal control of protein breakdown

Multiple lines of evidence suggest that the ubiquitin-proteasome-dependent proteolytic pathway is the major degradative process responsible for the lo ss of muscle proteins seen in various pathological states and following foo d deprivation. The first step in this pathway is the covalent attachment of polyubiquitin chains to protein substrates. This signal targets the substr ates for subsequent hydrolysis into peptides by the 26S proteasome. Several metabolic abnormalities (reduced food intake, Impaired mobility, and pertu rbations in the production or responsiveness of catabolic and anabolic horm ones, cytokines and/or proteolysis inducing factors) act in concert to cont ribute to muscle wasting in disease states. We cite recent evidence that in sulin, glucocorticoids, thyroid hormones, and nutrients regulate the rates of ubiquitinylation of protein substrates and of proteasome dependent prote olysis in skeletal muscle. (C) 2001 by the National Kidney Foundation, Inc.