Skeletal muscle is crucial for movement and whole-body metabolism; therefore, the maintenance of skeletal muscle mass is essential for mobility, disease prevention, and quality of life (20, 30). Skeletal muscle mass is ultimately determined by the net balance between the rate of protein degradation and the rate of protein synthesis (11). Thus, identifying the molecular mechanisms that regulate protein degradation and protein synthesis is critical for the development of effective exercise programs and potential pharmacological interventions that could inhibit muscle atrophy and/or promote hypertrophy.

Protein synthesis rates in skeletal muscle have been traditionally measured using various radioactive isotope (eg, 3H-phenyalanine or 35S-methionine), or stable isotope (eg, 15N-lysine, 13C-leucine, or (ring-13C6)-phenylalanine), tracers. These tracers are either constantly infused or given as a flooding dose, and the incorporation of the labeled amino acid into muscle proteins over time is then measured (for further review, see Davis and Reeds (4), Liu and Barrett (19), Reeds and Davis (25)). More recently, the nonYamino acidYstable isotope deuterium oxide (2H2O) also has been used to assess