Premium
Effect of hyperinsulinaemia–hyperaminoacidaemia on leg muscle protein synthesis and breakdown: reassessment of the two‐pool arterio‐venous balance model
Author(s) -
Smith Gordon I.,
Patterson Bruce W.,
Klein Seth J.,
Mittendorfer Bettina
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270774
Subject(s) - chemistry , amino acid , phenylalanine , protein catabolism , tracer , medicine , muscle hypertrophy , protein turnover , endocrinology , biochemistry , protein biosynthesis , biology , physics , nuclear physics
Key points Accurate measurements of muscle protein synthesis and breakdown rates are critical for understanding the processes underlying muscle atrophy and hypertrophy. Several mathematical approaches have been described to derive muscle protein synthesis and breakdown rates from a two‐pool (artery–vein) model including metabolic tracers. We found that only some of the published approaches provide accurate protein turnover rates and only when the computations are made with mole percent excess as the measure of tracer enrichment and the sum of tracer and tracee as the corresponding concentration in the artery and vein; errors, up to several‐fold in magnitude, result when computations are made with unlabelled concentration only, and/or enrichment expressed as tracer‐to‐tracee ratio or with any of the other equations (irrespective of how concentration and enrichment are expressed). Interpretation of muscle protein turnover rates and their validity requires careful attention to the mathematical approach used to calculate them.Abstract Accurate measurement of muscle protein turnover is critical for understanding the physiological processes underlying muscle atrophy and hypertrophy. Several mathematical approaches, used in conjunction with a tracer amino acid infusion, have been described to derive protein synthesis and breakdown rates from a two‐pool (artery–vein) model. Despite apparently common underlying principles, these approaches differ significantly (some seem to not take into account arterio‐venous shunting of amino acids, which comprises ∼80–90% of amino acids appearing in the vein) and most do not specify how tracer enrichment (i.e. mole percent excess (MPE) or tracer‐to‐tracee ratio (TTR)) and amino acid concentration (i.e. unlabelled only or total labelled plus unlabelled) should be expressed, which could have a significant impact on the outcome when using stable isotope labelled tracers. We developed equations that avoid these uncertainties and used them to calculate leg phenylalanine (Phe) kinetics in subjects who received a [ 2 H 5 ]Phe tracer infusion during postabsorptive conditions and during a hyperinsulinaemic–euglycaemic clamp with concomitant protein ingestion. These results were compared with those obtained by analysing the same data with previously reported equations. Only some of them computed the results correctly when used with MPE as the enrichment measure and total (tracer+tracee) Phe concentrations; errors up to several‐fold in magnitude were noted when the same approaches were used in conjunction with TTR and/or unlabelled concentration only, or when using the other approaches (irrespective of how concentration and enrichment are expressed). Our newly developed equations should facilitate accurate calculation of protein synthesis and breakdown rates.