QUANTIFICATION OF AMINO ACID TRANSPORT THROUGH INTERSTITIAL FLUID: ASSESSMENT OF FOUR COMPARTMENT MODELING FOR MUSCLE PROTEIN KINETICS.

Testosterone administration (T) increases lean body mass and muscle protein synthesis. We investigated the effects of short-term T on leg muscle protein kinetics and transport of selected amino acids by use of a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis (FSR) and breakdown (FBR) rates of skeletal muscle protein were also directly calculated. Seven healthy men were studied before and 5 days after intramuscular injection of 200 mg of testosterone enanthate. Protein synthesis increased twofold after injection ( P < 0.05), whereas protein breakdown was unchanged. FSR and FBR calculations were in accordance, because FSR increased twofold ( P < 0.05) without a concomitant change in FBR. Net balance between synthesis and breakdown became more positive with both methodologies ( P< 0.05) and was not different from zero. T injection increased arteriovenous essential and nonessential nitrogen balance across the leg ( P < 0.05) in the fasted state, without increasing amino acid transport. Thus T administration leads to an increased net protein synthesis and reutilization of intracellular amino acids in skeletal muscle.

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Relationship between transmembrane amino acid transport and protein kinetics in muscle tissue of severely burned patients

Clinical Nutrition ◽

10.1016/0261-5614(93)90172-z ◽

1993 ◽

Vol 12 ◽

pp. 4 ◽

Cited By ~ 12

Author(s):

G. Biolo ◽

S.P. Maggi ◽

R.Y.D. Fleming ◽

D.N. Herndon ◽

R.R. Wolfe

Keyword(s):

Amino Acid ◽

Muscle Tissue ◽

Amino Acid Transport ◽

Acid Transport ◽

Protein Kinetics

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In vivo muscle amino acid transport involves two distinct processes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00092.2004 ◽

2004 ◽

Vol 287 (1) ◽

pp. E136-E141 ◽

Cited By ~ 23

Author(s):

Sharon Miller ◽

David Chinkes ◽

David A. MacLean ◽

Dennis Gore ◽

Robert R. Wolfe

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Amino Acid Transport ◽

Interstitial Fluid ◽

Muscle Blood Flow ◽

Amino Acid Uptake ◽

Transport Systems ◽

Acid Uptake ◽

Acid Transport ◽

Rate Limiting

We have tested the hypothesis that transit through the interstitial fluid, rather than across cell membranes, is rate limiting for amino acid uptake from blood into muscle in human subjects. To quantify muscle transmembrane transport of naturally occurring amino acids, we developed a novel 4-pool model that distinguishes between the interstitial and intracellular fluid compartments. Transport kinetics of phenylalanine, leucine, lysine, and alanine were quantified using tracers labeled with stable isotopes. The results indicate that interstitial fluid is a functional compartment insofar as amino acid kinetics are concerned. In the case of leucine and alanine, transit between blood and interstitial fluid was potentially rate limiting for muscle amino acid uptake and release in the postabsorptive state. For example, in the case of leucine, the rate of transport between blood and interstitial fluid compared with the corresponding rate between interstitial fluid and muscle was 247 ± 36 vs. 610 ± 95 nmol·min−1·100 ml leg−1, respectively ( P < 0.05). Our results are consistent with the process of diffusion governing transit from blood to interstitial fluid without selectivity, and of specific amino acid transport systems with varying degrees of efficiency governing transit from interstitial fluid to muscle. These results imply that changes in factors that affect the transit of amino acids from blood through interstitial fluid, such as muscle blood flow or edema, could play a major role in controlling the rate of muscle amino acid uptake.

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Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.3.e514 ◽

1995 ◽

Vol 268 (3) ◽

pp. E514-E520 ◽

Cited By ~ 157

Author(s):

G. Biolo ◽

S. P. Maggi ◽

B. D. Williams ◽

K. D. Tipton ◽

R. R. Wolfe

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Resistance Exercise ◽

Amino Acid Transport ◽

Protein Turnover ◽

Muscle Protein ◽

Acid Transport ◽

Isotopic Tracers ◽

Muscle Protein Turnover ◽

Synthesis And Degradation

The rates of protein synthesis and degradation and of amino acid transport were determined in the leg muscle of untrained postabsorptive normal volunteers at rest and approximately 3 h after a resistance exercise routine. The methodology involved use of stable isotopic tracers of amino acids, arteriovenous catheterization of the femoral vessels, and biopsy of the vastus lateralis muscle. During postexercise recovery, the rate of intramuscular phenylalanine utilization for protein synthesis increased above the basal value by 108 +/- 18%, whereas the rate of release from proteolysis increased by 51 +/- 17%. Muscle protein balance improved (P < 0.05) after exercise but did not become positive (from -15 +/- 12 to -6 +/- 3 nmol phenylalanine.min-1.100 ml leg volume-1). After exercise, rates of inward transport of leucine, lysine, and alanine increased (P < 0.05) above the basal state from 132 +/- 16 to 208 +/- 29, from 122 +/- 8 to 260 +/- 8, and from 384 +/- 71 to 602 +/- 89 nmol.min-1.100 ml leg-1, respectively. Transport of phenylalanine did not change significantly. These results indicate that, during recovery after resistance exercise, muscle protein turnover is increased because of an acceleration of synthesis and degradation. A postexercise acceleration of amino acid transport may contribute to the relatively greater stimulation of protein synthesis.

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Protein turnover and amino acid transport kinetics in end-stage renal disease

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00352.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. E136-E143 ◽

Cited By ~ 38

Author(s):

Dominic S. C. Raj ◽

Philip Zager ◽

Vallbh O. Shah ◽

Elizabeth A. Dominic ◽

Oladipo Adeniyi ◽

...

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Amino Acid Transport ◽

Protein Turnover ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Transport Kinetics ◽

Acid Transport ◽

Intracellular Amino Acid ◽

Stage Renal Disease

Protein and amino acid metabolism is abnormal in end-stage renal disease (ESRD). Protein turnover is influenced by transmembrane amino acid transport. The effect of ESRD and hemodialysis (HD) on intracellular amino acid transport kinetics is unknown. We studied intracellular amino acid transport kinetics and protein turnover by use of stable isotopes of phenylalanine, leucine, lysine, alanine, and glutamine before and during HD in six ESRD patients. Data obtained from amino acid concentrations and enrichment in the artery, vein, and muscle compartments were used to calculate intracellular amino acid transport and muscle protein synthesis and catabolism. Fractional muscle protein synthesis (FSR) was estimated by the precursor product approach. Despite a significant decrease in the plasma concentrations of amino acids in the artery and vein during HD, the intracellular concentrations remained stable. Outward transport of the amino acids was significantly higher than the inward transport during HD. FSR increased during HD (0.0521 ± 0.0043 vs. 0.0772 ± 0.0055%/h, P < 0.01). Results derived from compartmental modeling indicated that both protein synthesis (118.3 ± 20.6 vs. 146.5 ± 20.6 nmol·min-1·100 ml leg-1, P < 0.01) and catabolism (119.8 ± 18.0 vs. 174.0 ± 14.2 nmol·min-1·100 ml leg-1, P < 0.01) increased during HD. However, the intradialytic increase in catabolism exceeded that of synthesis (57.8 ± 13.8 vs. 28.0 ± 8.5%, P < 0.05). Thus HD alters amino acid transport kinetics and increases protein turnover, with net increase in protein catabolism.

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