Determinants of protein turnover in health and disease

Protein synthesis, protein degradation, and amino acid oxidation are tightly regulated to preserve lean body mass in healthy individuals. An adaptative response to a reduction in dietary protein in normal adults is decreased branched-chain amino acid oxidation which increases the availability of amino acids. In nephrosis, reduced branched-chain amino acid oxidation decreases amino acid requirements and helps to compensate for urinary protein loss. Conversely, uremia and other catabolic diseases are associated with muscle wasting resulting from activation of the ubiquitin-proteasome proteolytic pathway and branched-chain ketoacid dehydrogenase, the rate-limiting enzyme for branched-chain amino acid catabolism. By understanding the processes responsible for muscle wasting in catabolic states, therapeutic interventions may be designed to improve protein balance.