Protein turnover and amino acid transport kinetics in end-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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Testosterone injection stimulates net protein synthesis but not tissue amino acid transport

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.275.5.e864 ◽

1998 ◽

Vol 275 (5) ◽

pp. E864-E871 ◽

Cited By ~ 48

Author(s):

Arny A. Ferrando ◽

Kevin D. Tipton ◽

David Doyle ◽

Stuart M. Phillips ◽

Joaquin Cortiella ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Amino Acid Transport ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Acid Transport ◽

Skeletal Muscle Protein ◽

Net Protein

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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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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Human muscle protein synthesis and breakdown during and after exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.91481.2008 ◽

2009 ◽

Vol 106 (6) ◽

pp. 2026-2039 ◽

Cited By ~ 148

Author(s):

Vinod Kumar ◽

Philip Atherton ◽

Kenneth Smith ◽

Michael J. Rennie

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Protein Turnover ◽

Acute Exercise ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Mitochondrial Protein ◽

Human Muscle ◽

Muscle Protein Turnover ◽

Amino Acid Availability

Skeletal muscle demonstrates extraordinary mutability in its responses to exercise of different modes, intensity, and duration, which must involve alterations of muscle protein turnover, both acutely and chronically. Here, we bring together information on the alterations in the rates of synthesis and degradation of human muscle protein by different types of exercise and the influences of nutrition, age, and sexual dimorphism. Where possible, we summarize the likely changes in activity of signaling proteins associated with control of protein turnover. Exercise of both the resistance and nonresistance types appears to depress muscle protein synthesis (MPS), whereas muscle protein breakdown (MPB) probably remains unchanged during exercise. However, both MPS and MPB are elevated after exercise in the fasted state, when net muscle protein balance remains negative. Positive net balance is achieved only when amino acid availability is increased, thereby raising MPS markedly. However, postexercise-increased amino acid availability is less important for inhibiting MPB than insulin, the secretion of which is stimulated most by glucose availability, without itself stimulating MPS. Exercise training appears to increase basal muscle protein turnover, with differential responses of the myofibrillar and mitochondrial protein fractions to acute exercise in the trained state. Aging reduces the responses of myofibrillar protein and anabolic signaling to resistance exercise. There appear to be few, if any, differences in the response of young women and young men to acute exercise, although there are indications that, in older women, the responses may be blunted more than in older men.

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Amino Acid Transport Kinetics and Protein Turnover in Hemodialysis

Hemodialysis International ◽

10.1046/j.1492-7535.2003.01267.x ◽

2003 ◽

Vol 7 (1) ◽

pp. 73-104

Author(s):

Raj Dominic ◽

Blandon Pedro ◽

Ferrando Arny ◽

Adeniyi Oladipo ◽

Shah Vallabh ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Transport ◽

Protein Turnover ◽

Transport Kinetics ◽

Acid Transport

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Effects of high versus standard essential amino acid intakes on whole-body protein turnover and mixed muscle protein synthesis during energy deficit: A randomized, crossover study

Clinical Nutrition ◽

10.1016/j.clnu.2020.07.019 ◽

2020 ◽

Cited By ~ 3

Author(s):

Jess A. Gwin ◽

David D. Church ◽

Adrienne Hatch-McChesney ◽

Emily E. Howard ◽

Christopher T. Carrigan ◽

...

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Protein Turnover ◽

Essential Amino Acid ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Energy Deficit ◽

Whole Body ◽

Body Protein ◽

Randomized Crossover Study

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Protein turnover, growth and proliferation in CHO cells. Variation within and between mutant classes for salvage pathway enzymes

Biochemical Journal ◽

10.1042/bj2820049 ◽

1992 ◽

Vol 282 (1) ◽

pp. 49-57 ◽

Cited By ~ 2

Author(s):

J M Gunn ◽

M R Brancheau

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Protein Degradation ◽

Amino Acid Transport ◽

Cho Cells ◽

Protein Turnover ◽

Transport Protein ◽

Clonal Variation ◽

Acid Transport ◽

Salvage Pathways

We have examined the clonal variation in rates of amino acid transport, protein synthesis, protein degradation, growth and proliferation for CHO cells with mutations in the purine and pyrimidine salvage pathways. First we compared three clonal cell lines, each with a different mutation, with the heterozygous parental line AT3-2. Overall, the correlation between rates of protein turnover, growth and proliferation was excellent. The slower growth and proliferation of one mutant, AB3 (TK-, APRT-), is explained by a low intrinsic rate of protein synthesis coupled with a smaller response in rates of amino acid transport, protein synthesis and protein degradation to insulin, serum and dexamethasone. Secondly, we compared seven aza-adenine-resistant and 14 thioguanine-resistant mutants of AT3-2 and found significant differences in control and insulin-stimulated rates of protein turnover both within and between mutant populations. A significant difference between the populations was unexpected because each individual cell line was cloned from a spontaneous pre-existing mutation in AT3-2, and each population should have the same average rate. Remarkably, all 24 mutants had lower rates of protein synthesis than AT3-2. We cannot explain the data solely in terms of mutations in the salvage pathways. Rather, we propose that the mutant survivors have randomly down-regulated the intrinsically fixed growth factor-regulated pathways of protein turnover, resulting in a broad spectrum of lower metabolic rates.

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