Human muscle protein turnover--why is it so variable?
We undertook a comprehensive review of the literature to unravel the nature of the variability in the reported rate of human muscle protein synthesis. We analyzed the results from studies that report the protein fractional synthesis rate (FSR) in the vastus lateralis in healthy, nonobese, untrained adults ≤50 yr of age in the postabsorptive state at rest by using the primed, constant tracer amino acid infusion method according to experimental design characteristics. We hypothesized that if the variability is methodological (rather than physiological) in nature, systematic clustering of FSR values would be evident, and outliers would become apparent. Overall, as expected, the mixed muscle protein FSR values were significantly (P < 0.001) greater when the muscle vs. the plasma free amino acid enrichment is used as the surrogate precursor pool enrichment, and the average mixed muscle protein FSR values were significantly greater (P = 0.05) than the myofibrillar/myosin heavy chain FSR values. The within-study variability (i.e., population variance) was somewhat smaller in studies that used plasma amino acid/ketoacid enrichments vs. muscle free amino acid enrichment (∼24 vs. ∼31%), but this was not apparent in all circumstances. Furthermore, the between-study consistency of measured FSR values (i.e., interquartile range) was inversely correlated with the average duration between biopsies. Aside from that, the variation in reported FSR values could not be explained by differences in the experimental design and analytical methods, and none of the most commonly used approaches stood out as clearly superior in terms of consistency of results and/or within-study variability. We conclude that the variability in reported values is in part due to 1) differences in experimental design (e.g., choice of precursor pool) and 2) considerable within-subject variability. The summary of the results from our analysis can be used as guidelines for "normal" average basal FSR values at rest in healthy adults.
Division of Geriatrics and Nutritional Science, Washington Univ. School of Medicine, 660 South Euclid Ave., Campus Box 8031, St. Louis, MO 63110, USA.
Gordon I
GI
Smith
Bruce W
BW
Patterson
Bettina
B
Mittendorfer
D000328:Adult; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism*
D009124:Muscle Proteins