Mechanisms of protein degradation: what do the rat studies tell us.

Uremia induces substantial changes in protein metabolism. The branched-chain amino acids serve as useful markers of these changes and their catabolism is increased in uremia, particularly in the presence of metabolic acidosis. Glucocorticoids also are involved in accelerating protein degradation, and the negative nitrogen balance which results in loss of lean body mass. Cellular mechanisms accounting for these changes include an up-regulation of the ubiquitin-proteasome pathway and branched-chain ketoacid dehydrogenase activity in muscle. A low insulin level also appears to play a permissive role in causing increased catabolism. These findings have important clinical implications because correction of the metabolic acidosis with alkali blunts these responses and improves nutritional status.