METABOLIC-ACIDOSIS STIMULATES PROTEIN-METABOLISM IN UREMIA

It is well established that chronic renal failure is associated with l oss of lean body mass. Possible explanations for protein losses includ e a limited ability to reduce essential amino acid oxidation and prote in degradation when dietary protein is low. Alternatively, uremia coul d directly stimulate protein catabolism. In rats, we have uncovered ev idence that metabolic acidosis not only blunts the responses to a low- protein diet but also stimulates the degradation of muscle protein, We find that the ATP-ubiquitin-proteasome-dependent pathway causing musc le protein degradation is activated by acidosis. Glucocorticoids are r equired but are not sufficient to elicit this catabolic response.