Effect of Infused Branched-Chain Amino Acids on Muscle and Whole-Body Amino Acid Metabolism in Man

1990 ◽  
Vol 79 (5) ◽  
pp. 457-466 ◽  
Author(s):  
Rita J. Louard ◽  
Eugene J. Barrett ◽  
Robert A. Gelfand
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Branched Chain Amino Acid ◽  
Branched Chain

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 μ-units/ml). 3. Whole-body phenylalanine flux, an index of proteolysis, was significantly suppressed by branched-chain amino acid infusion (P < 0.002), and forearm phenylalanine production was also inhibited (P < 0.03). With branched-chain amino acid infusion total leucine flux rose, with marked increments in both oxidative and non-oxidative leucine disposal (P < 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 < 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.

scholarly journals Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids

1988 ◽  
Vol 254 (2) ◽  
pp. 579-584 ◽  
Author(s):  
P J Garlick ◽  
I Grant
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Branched Chain Amino Acids ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Branched Chain

Rates of muscle protein synthesis were measured in vivo in tissues of post-absorptive young rats that were given intravenous infusions of various combinations of insulin and amino acids. In the absence of amino acid infusion, there was a steady rise in muscle protein synthesis with plasma insulin concentration up to 158 mu units/ml, but when a complete amino acids mixtures was included maximal rates were obtained at 20 mu units/ml. The effect of the complete mixture could be reproduced by a mixture of essential amino acids or of branched-chain amino acids, but not by a non-essential mixture, alanine, methionine or glutamine. It is concluded that amino acids, particularly the branched-chain ones, increase the sensitivity of muscle protein synthesis to insulin.

Removal of infused amino acids by splanchnic and leg tissues in humans

1986 ◽  
Vol 250 (4) ◽  
pp. E407-E413 ◽  
Author(s):  
R. A. Gelfand ◽  
M. G. Glickman ◽  
R. Jacob ◽  
R. S. Sherwin ◽  
R. A. DeFronzo
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Branched Chain Amino Acids ◽  
Acid Uptake ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Significant Uptake ◽  
Branched Chain

To compare the contributions of splanchnic and skeletal muscle tissues to the disposal of intravenously administered amino acids, regional amino acid exchange was measured across the splanchnic bed and leg in 11 normal volunteers. Postabsorptively, net release of amino acids by leg (largely alanine and glutamine) was complemented by the net splanchnic uptake of amino acids. Amino acid infusion via peripheral vein (0.2 g X kg-1 X h-1) caused a doubling of plasma insulin and glucagon levels and a threefold rise in blood amino acid concentrations. Both splanchnic and leg tissues showed significant uptake of infused amino acids. Splanchnic tissues accounted for approximately 70% of the total body amino acid nitrogen disposal; splanchnic uptake was greatest for the glucogenic amino acids but also included significant quantities of branched-chain amino acids. In contrast, leg amino acid uptake was dominated by the branched-chain amino acids. Based on the measured leg balance, body skeletal muscle was estimated to remove approximately 25-30% of the total infused amino acid load and approximately 65-70% of the infused branched-chain amino acids. Amino acid infusion significantly stimulated both the leg efflux and the splanchnic uptake of glutamine (not contained in the infusate). We conclude that when amino acids are infused peripherally in normal humans, splanchnic viscera (liver and gut) are the major sites of amino acid disposal.

Increase in anterior tibialis muscle protein synthesis in healthy man during mixed amino acid infusion: studies of incorporation of [1−13C]leucine

1989 ◽  
Vol 76 (4) ◽  
pp. 447-454 ◽  
Author(s):  
W. M. Bennet ◽  
A. A. Connacher ◽  
C. M. Scrimgeour ◽  
K. Smith ◽  
M. J. Rennie
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Body Protein ◽  
Anterior Tibial Muscle ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Anterior Tibial

1. Anterior tibial muscle protein synthesis in seven healthy postabsorptive men was determined from increases in muscle protein bound leucine enrichment during a primed continuous infusion of l-[1−13C]leucine. Biopsies were taken 30 min after the beginning of leucine infusion (when plasma 13C enrichment was steady), 240 min later during continued fasting and again after 240 min of infusion of a mixed amino acid solution which increased plasma total amino acid concentrations by 37%. The mean enrichment of 13C in plasma α-ketoisocaproate was used as an index of the enrichment of the precursor pool for leucine metabolism. 2. Anterior tibial muscle mixed protein synthetic rate during fasting was 0.055 (sd 0.008) %/h and this increased by an average of 35% during infusion of mixed amino acid to 0.074 (sd 0.021) %/h (P < 0.05). 3. Whole-body protein breakdown (expressed as the rate of endogenous leucine appearance in plasma) was 121 (sd 8) μmol h−1 kg−1 during fasting and decreased (P < 0.01) by an average of 12% during amino acid infusion. Leucine oxidation was 18 (sd 3) μmol h−1 kg−1 during fasting and increased (P < 0.001) by 89% during amino acid infusion. Whole-body protein synthesis (non-oxidative leucine disappearance) was 104 (sd 6) μmol h−1 kg−1 during fasting and rose by 13% (P < 0.001) during mixed amino acid infusion. 4. 13C enrichment of muscle free leucine was only 61 (sd 19) % of that in plasma α-ketoisocaproate and this increased to 74 (sd 16) % (P < 0.02) during mixed amino acid infusion. 5. The results suggest that increased availability of amino acids reverses whole-body protein balance from negative to positive and a major component of this is the increase in muscle protein synthesis.

Response of rat heart and skeletal muscle protein in vivo to insulin and amino acid infusion

1993 ◽  
Vol 264 (6) ◽  
pp. E958-E965 ◽  
Author(s):  
P. H. McNulty ◽  
L. H. Young ◽  
E. J. Barrett
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Protein ◽  
Acid Infusion ◽  
Amino Acid Infusion

Whether insulin, at physiological concentrations, stimulates net muscle protein synthesis in vivo remains unresolved. To examine this, we infused either saline, insulin (2.8 mU.kg-1.min-1, euglycemic clamp), an amino acid solution, or insulin plus amino acids for 4 h into awake overnight-fasted rats. Heart and skeletal muscle protein synthesis was measured by either a continuous tracer infusion method, using L-[1-14C]leucine, L-[2,5-3H]leucine, or L-[ring-2,6-3H]phenylalanine or by injection of L-[ring-2,6-3H]phenylalanine with a pool-flooding bolus of unlabeled phenylalanine. In heart, synthesis rates obtained using the arterial plasma specific activity of [3H]phenylalanine administered as either a tracer infusion or flooding bolus were comparable in saline-treated rats (range 10.9 +/- 1.2 to 12.2 +/- 0.9%/day) and were not affected by infusion of insulin or amino acids. Estimates using continuous infusion of L-[1-14C]leucine were significantly lower (P < 0.001), except when unlabeled amino acids were given also. In skeletal muscle, rates estimated using the flooding bolus (6.7 +/- 0.8%/day) were also not affected by insulin or amino acids. Estimates using continuous infusion of [3H]leucine (2.6 +/- 0.3%/day) or [3H]phenylalanine (2.8 +/- 1.0%/day) were lower and were still lower using [14C]leucine (1.6 +/- 0.6%/day), but increased toward those estimated with the flooding bolus during amino acid infusion. We conclude that, in heart muscle of the mature rat in vivo, neither insulin nor amino acids affect protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

2007 ◽  
Vol 292 (6) ◽  
pp. E1534-E1542 ◽  
Author(s):  
Dominic S. C. Raj ◽  
Oladipo Adeniyi ◽  
Elizabeth A. Dominic ◽  
Michel A. Boivin ◽  
Sandra McClelland ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Breakdown ◽  
Protein Catabolism ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Muscle Protein Breakdown

Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol·min−1·100 ml −1) was more negative during HD-O compared with pre-HD (−33.7 ± 1.5 vs. −6.0 ± 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (−16.9 ± 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively ( P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

scholarly journals Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans

2016 ◽  
Vol 311 (4) ◽  
pp. E671-E677 ◽  
Author(s):  
Sarah Everman ◽  
Christian Meyer ◽  
Lee Tran ◽  
Nyssa Hoffman ◽  
Chad C. Carroll ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Insulin Infusion ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Essential Amino Acids ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Synthesis Rate ◽  
Branched Chain

Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change ( P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased ( P < 0.01) whole body phenylalanine rate of appearance (μmol·kg−1·min−1), indicating suppression of muscle proteolysis, in both the control (1.02 ± 0.04 vs 0.76 ± 0.04) and the BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments ( P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA.

scholarly journals Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs

2017 ◽  
Vol 117 (7) ◽  
pp. 911-922 ◽  
Author(s):  
Liufeng Zheng ◽  
Fangrui Zuo ◽  
Shengjun Zhao ◽  
Pingli He ◽  
Hongkui Wei ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Dietary Supplementation ◽  
Branched Chain Amino Acids ◽  
Young Pigs ◽  
Branched Chain ◽  
Net Fluxes ◽  
Venous Plasma

AbstractBranched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

Sign in / Sign up

Export Citation Format

Share Document