Proteins in skeletal muscle, as in other cells, are subject to continuous turnover, and the overall rate of protein breakdown in this tissue, like the rate of synthesis, is precisely controlled. The regulation of proteolysis in muscle is important in overall energy homeostasis, in the control of muscle mass and body growth, and also in adaptations of the organism to a variety of stressful conditions. Because skeletal muscle constitutes the major protein reservoir in the body, the hydrolysis of muscle proteins to generate amino acids is an important first step in gluconeogenesis. Consequently, negative protein balance in muscle, leading to a net loss of soluble and myofibrillar proteins, is characteristic of physiological states where gluconeogenesis from body protein stores rises, such as starvation, diabetes, and sepsis. Thus, it is not surprising that overall rates of protein synthesis and degradation in muscle are regulated by a number of hormones that are also critical in energy homeostasis, including insulin and cortisol.

Because the bulk of muscle proteins, especially the contractile components, turn over rather slowly under normal conditions, a reduction in muscle protein synthesis in fasting would by itself supply amino acids to the organism relatively slowly. Thus, in fasting, an increase in protein breakdown in muscle appears to be a critical adaptation in promoting the rapid mobilization of amino acids. On the other hand, in certain physiological states, continued viability requires the preservation of cell proteins and reduced intracellular proteolysis. For example, with insufficient dietary intake of proteins or in prolonged starvation (where calories are available from lipid stores), the continued mobilization of cell proteins could be