Metabolic acidosis stimulates protein metabolism in uremia.

It is well established that chronic renal failure is associated with loss of lean body mass. Possible explanations for protein losses include a limited ability to reduce essential amino acid oxidation and protein degradation when dietary protein is low. Alternatively, uremia could directly stimulate protein catabolism. In rats, we have uncovered evidence 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 muscle protein degradation is activated by acidosis. Glucocorticoids are required but are not sufficient to elicit this catabolic response.