Regulation of Protein Synthesis and Skeletal Muscle Growth

From this presentation it emerges that there are several potentially important points of control in muscle protein synthesis and its regulation is achieved through a variety of mechanisms. However, various parameters of protein synthesis change in a coordinated way during the process of normal growth and under conditions leading to atrophy or hypertrophy of the muscle mass. Thus, the identity of the rate limiting step(s) in muscle protein synthesis and the quantitative significance of the factors which affect them in the well-nourished animal remains to be established. Regulatory mechanisms exist which are important in the adaptive response of muscle protein synthesis to short-term changes in the internal and external environment. These involve, for example, changes in the relative rates of polypeptide chain initiation and elongation. On the other hand, the availability of muscle ribosomes appears to have a longer-term regulatory significance and these different mechanisms are integrated at the cellular level and function in a cooperative way to determine the rate at which muscle proteins are synthesized and accumulated. Furthermore, the various mechanisms are also responsive to changes occurring in the different cell and organ systems of the body. Finally, the importance of function and participation of neural, hormonal and nutritional influences on muscle growth are well recognized but we do not understand how these factors are translated into the appropriate protein synthetic response in this tissue. The associations between the biochemical aspects of muscle protein synthesis and the structural organization of the differentiated muscle cell require considerable further exploration and the development of in vitro systems which reflect as closely as possible the behaviour of the intact cell are needed in order to fill these large gaps in our understanding of muscle protein synthesis and its regulation. Ultimately this will allow a rational approach to the manipulation of muscle growth for a given set of circumstances.