Effect of infused branched-chain amino acids on muscle and whole-body amino acid metabolism in man.
1. Using the forearm balance method, together with systemic infusions of L-[ring-2,6-3H]phenylalanine and L-[1-14C]leucine, we examined the effects of infused branched-chain amino acids on whole-body and skeletal muscle amino acid kinetics in 10 postabsorptive normal subjects; 10 control subjects received only saline. 2. Infusion of branched-chain amino acids caused a four-fold rise in arterial branched-chain amino acid levels and a two-fold rise in branched-chain keto acids; significant declines were observed in circulating levels of most other amino acids, including phenylalanine, which fell by 34%. Plasma insulin levels were unchanged from basal levels (8 +/- 1 mu-units/ml). 3. Whole-body phenylalanine flux, an index of proteolysis, was significantly suppressed by branched-chain amino acid infusion (P less than 0.002), and forearm phenylalanine production was also inhibited (P less than 0.03). With branched-chain amino acid infusion total leucine flux rose, with marked increments in both oxidative and non-oxidative leucine disposal (P less than 0.001). Proteolysis, as measured by endogenous leucine production, showed a modest 12% decrease, although this was not significant when compared with saline controls. The net forearm balance of leucine and other branched-chain amino acids changed from a basal net output to a marked net uptake (P less than 0.001) during branched-chain amino acid infusion, with significant stimulation of local leucine disposal. Despite the rise in whole-body non-oxidative leucine disposal, and in forearm leucine uptake and disposal, forearm phenylalanine disposal, an index of muscle protein synthesis, was not stimulated by infusion of branched-chain amino acids. 4. The results suggest that in normal man branched-chain amino acid infusion suppresses skeletal muscle proteolysis independently of any rise of plasma insulin. Muscle branched-chain amino acid uptake rose dramatically in the absence of any apparent increase in muscle protein synthesis, as measured by phenylalanine disposal, or in branched-chain keto acid release. Thus, an increase in muscle branched-chain amino acid concentrations and/or local branched-chain amino acid oxidation must account for the increased disposal of branched-chain amino acids.
Louard
R J
RJ
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Barrett
E J
EJ
Gelfand
R A
RA
D000293:Adolescent; D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005542:Forearm; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D010649:Phenylalanine / Q000008:administration & dosage / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine; D007930:Leucine