Basal muscle intracellular amino acid kinetics in women and men

Abstract

Sexual dimorphism in skeletal muscle mass is apparent, with men having more muscle mass and larger individual muscle cells. However, no sex-based differences have been detected in blood forearm phenylalanine turnover, although whole body leucine oxidation has been reported to be greater in men than in women. We hypothesized that sex differences in intracellular amino acid turnover may account for these discrepancies, with men having a higher intracellular turnover than women. We studied young, healthy women (women, n = 8) and men (men, n = 10) following an overnight fast. Phenylalanine, leucine, and alanine muscle intracellular kinetics were assessed using stable isotope methodologies, femoral arteriovenous blood sampling, and muscle biopsies. Muscle intracellular amino acid kinetics were reported relative to both leg volume and lean leg mass because of sex differences in leg volume and in muscle and fat distribution. When expressed per leg volume (nmol.min(-1).100 ml leg volume(-1)), phenylalanine net balance (women: -16 +/- 4, men: -31 +/- 5), release from proteolysis in the blood (women: 46 +/- 9, men: 75 +/- 10) and intracellular availability (women: 149 +/- 23, men: 241 +/- 35), and alanine production, utilization, and intracellular availability were higher in men (P < 0.05). However, when the kinetic parameters were normalized per unit of lean leg mass, all differences disappeared. Muscle fractional synthetic rate was also not different between women and men. We conclude that there are no sex-based differences in basal muscle intracellular amino acid turnover when the data are normalized by lean mass. It remains to be determined if there are sex differences in intracellular amino acid metabolism following anabolic or catabolic stimuli.

Figures

Fig. 1

Two- and three-pool models of leg amino acid kinetics. Free amino acid pools in femoral artery (A), femoral vein (V), and muscle (M) are connected by arrows indicating unidirectional amino acid flow between each compartment. With both models, amino acids enter the leg via the femoral artery (Fin) and leave the leg via the femoral vein (Fout). Two-pool model: Rd, rate of amino acid disappearance (an estimate of muscle protein synthesis when using the phenylalanine tracer, and synthesis and oxidation when using the leucine and alanine tracers); Ra, rate of amino acid appearance in blood from breakdown (with phenylalanine and leucine), or breakdown and de novo synthesis (with alanine). Three-pool model: FV,A, direct amino acid flow from artery to vein without entering intracellular pool; FM,A and FV,M, inward and outward amino acid transport from artery to muscle and from muscle to vein, respectively; FM,0, rate of intracellular appearance from proteolysis (with phenylalanine and leucine), or proteolysis and de novo synthesis (with alanine); F0,M, intracellular amino acid utilization for protein synthesis (with phenylalanine), or synthesis and oxidation (with leucine and alanine); r, amino acid recycling from breakdown into synthesis (with phenylalanine).

Fig. 2

Mixed muscle protein fractional synthesis rate (FSR). Error bars indicate SE.