Factors Affecting Muscle Mass – Dr. Mauro DiPasquale

The factors underlying variations in protein synthesis and catabolism, which regulate muscle mass, are complex and still being worked out. However, we have enough information now to allow us to manipulate both processes and increase muscle accretion. While difficult to understand, and even tedious at times, the principles behind the regulation of protein metabolism are worth knowing about since they underlie much of what we do in our attempts to maximize body composition and exercise performance.

For example, amino acids, while important as substrates for various metabolic pathways, are also regulators of protein synthesis and other metabolic processes.

We know that like exercise, amino acids increase protein synthesis with the signaling pathways influencing mTOR (mammalian target of rapamycin), which in turn stimulates protein synthesis. ^1,2

Accelerated protein breakdown and a net protein loss occur secondary to exhaustive exercise and in injury and various diseases. The negative nitrogen balance observed in such cases represents the net result of breakdown and synthesis; with breakdown increased and synthesis either increased or diminished. Under certain conditions protein catabolism can also be decreased. As well, protein synthesis can be increased or decreased under certain conditions. The net result depends on the conditions present and the effects on both synthesis and catabolism.

For example, in order to have a net increase in protein synthesis so that there is an increase in the concentration of a protein in a cell, its rate of synthesis would have to increase or its breakdown decrease or both. There are at least four ways in which the concentration of protein in a cell could be changed:

• The rate of synthesis of the mRNA that codes for the particular protein(s) could be increased (known as transcriptional control).
• The rate of synthesis of the polypeptide chain by the ribosomal-mRNA complex could be increased (known as translational control).
• The rate of degradation of the mRNA could be decreased (also translational control).
• The rate of degradation of the protein could be decreased. The following table outlines some of the conditions or factors affecting protein synthesis. Many of these conditions and factors are inter-related. Keep in mind that protein synthesis is increased as the result of a net positive change secondary to changes in both (or less commonly one of) synthesis and catabolism.

i. Cellular hydration refers to an intracellular state and as such is different from extracellular hydration.

ii. Thyroid hormone (thyroxine and triiodothyronine) stimulate both protein synthesis and degradation depending on their levels in the body. Not enough or too much can be detrimental to protein synthesis. Higher than normal levels of thyroid hormone leads to the catabolism of protein.

** From Amino Acids and Proteins for the Athlete, the Anabolic Edge, Mauro DiPasquale, M.D., 2nd Edition in Press.

The amount of protein synthesis that takes place during and after exercise is dependent on several factors including a complete complement of precursor amino acids (both essential and non-essential amino acids), specific acetylating enzymes, tRNA, and adequate ATP levels. While the relation of protein synthesis to the ambient concentrations of amino acids in the intracellular and extracellular pools has not been fully defined, it is possible to identify sets of intracellular amino acids that predict the level of protein synthesis, and to delineate combinations of plasma amino acids whose levels account for a significant portion of the variance in the intracellular predictor amino acids in normal human infants and adults.

In one study the intracellular concentrations of most amino acids were found to be higher than their concentrations in plasma, except for valine and citrulline, which were lower.3 The “aminograms” in the two pools also were very different – 44% of the variance in protein synthesis was accounted for by the intracellular concentrations of leucine, glycine, alanine, and taurine in neonates, and 45% by a combination of threonine, valine, methionine, and histidine in adults. The intracellular concentrations of each of these predictor amino acids in adults were, in turn, related to different combinations of the plasma concentrations of threonine, phenylalanine, tryptophan, isoleucine, histidine, citrulline, ornithine, arginine, and glycine.

The increases in intracellular amino acid concentrations seen with exercise may reflect decreased protein synthesis, accelerated protein catabolism, an increase in amino acid transport into the cell, or combinations of these conditions. For example an increase in protein synthesis would be expected to cause a decrease in amino acids but this may be offset by an increase in intracellular availability due to increased transport. As well, altered intracellular amino acid levels may directly regulate exchange diffusion of intracellular for extracellular amino acid(s).

Effects of Exercise on Protein Synthesis and Degradation Acute bouts of exercise can induce measurable changes in protein, carbohydrate, and lipid metabolism. These changes are characterized by a change in protein catabolism and synthesis and an increased utilization of protein for gluconeogenesis and lipids for oxidative fuel.^4,5,6,7 Chronic daily exercise leads to adaptive processes that result in a net increase in total body as well as peripheral nitrogen stores. ⁸

Exercise has profound effects on protein synthesis and degradation, and on the endogenous anabolic and catabolic hormones, which in turn modulate the adaptation response to exercise. ^{9,10,11,12,13,14,15,16,17,18,19,20} In general protein synthesis is suppressed during exercise while protein degradation appears to be increased; while in the recovery period during which hypertrophy occurs, protein synthesis is increased while protein degradation is suppressed in those muscle bearing the greatest load. ^{21,22,23,24,25,26,27}

References Available Upon Request

:: Dr. Mauro Di Pasquale :: is one of the most influential voices on diet, performance and athletic training in the world. His innovative work in finding safe nutritional alternatives to anabolic steroids and other performance-enhancing drugs has won him praise from athletes, trainers and fitness experts around the globe. Dr. Di Pasquale was a world-class athlete for over 15 years, winning the World Championships in powerlifting in 1976 and world games in 1981.