Assessing the Role of Muscle Protein Breakdown in Response to Nutrition and Exercise in Humans

Abstract

Muscle protein breakdown (MPB) is an important metabolic component of muscle remodeling, adaptation to training, and increasing muscle mass. Degradation of muscle proteins occurs via the integration of three main systems-autophagy and the calpain and ubiquitin-proteasome systems. These systems do not operate independently, and the regulation is complex. Complete degradation of a protein requires some combination of the systems. Determination of MPB in humans is technically challenging, leading to a relative dearth of information. Available information on the dynamic response of MPB primarily comes from stable isotopic methods with expression and activity measures providing complementary information. It seems clear that resistance exercise increases MPB, but not as much as the increase in muscle protein synthesis. Both hyperaminoacidemia and hyperinsulinemia inhibit the post-exercise response of MPB. Available data do not allow a comprehensive examination of the mechanisms behind these responses. Practical nutrition recommendations for interventions to suppress MPB following exercise are often made. However, it is likely that some degree of increased MPB following exercise is an important component for optimal remodeling. At this time, it is not possible to determine the impact of nutrition on any individual muscle protein. Thus, until we can develop and employ better methods to elucidate the role of MPB following exercise and the response to nutrition, recommendations to optimize post exercise nutrition should focus on the response of muscle protein synthesis. The aim of this review is to provide a comprehensive examination of the state of knowledge, including methodological considerations, of the response of MPB to exercise and nutrition in humans.

Fig. 1

Methods of assessing skeletal muscle protein breakdown (MPB). Skeletal muscle proteins are broken down by a combination of the three main protein breakdown systems. These breakdown systems do not work in isolation but rather work together to remodel skeletal muscle. (1) The calpain proteases disassemble myofibrils into smaller component parts, (2) the ubiquitin-proteasome system degrades these component into individual amino acids, and can label proteins (membrane receptors, channels and transporters) for destruction by the third system, (3) the autophagy-lysosome system, which predominantly breaks down membrane based proteins. Dynamic MPB measures use labelled amino-acid tracers (such as phenylalanine stable-isotopes) and provide a dynamic view of whole MPB. 3-Methylhistidine is a unique metabolite of myofibrillar protein breakdown and its appearance in blood and urine can be assumed to have come from the processes of myofibrillar protein breakdown. Skeletal muscle is the body’s largest depot of myofibrillar protein so changes in plasma/urinary/interstitial 3-methylhistidine are believed reflective of skeletal MPB. Other static markers of protein breakdown include the assessment of the messenger RNA (mRNA)/protein expression/activity/localization of components of the breakdown machinery. Markers are available to estimate changes in the activity of each of the three breakdown systems. L-Phe l-phenylalanine, AV arterio-venous, MuRF muscle ring finger protein, FKHR forkhead transcription factor