scholarly journals Amino Acids Stimulate Translation Initiation and Protein Synthesis through an Akt-Independent Pathway in Human Skeletal Muscle

2002 ◽  
Vol 87 (12) ◽  
pp. 5553-5558 ◽  
Author(s):  
Zhenqi Liu ◽  
Linda A. Jahn ◽  
Liping Wei ◽  
Wen Long ◽  
Eugene J. Barrett
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Human Skeletal Muscle

Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle

2001 ◽  
Vol 281 (3) ◽  
pp. E466-E471 ◽  
Author(s):  
Jeffrey S. Greiwe ◽  
Guim Kwon ◽  
Michael L. McDaniel ◽  
Clay F. Semenkovich
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
S6 Kinase ◽  
Signaling Mechanism ◽  
Insulin Resistant ◽  
Branched Chain ◽  
Plasma Leucine

Amino acids and insulin have anabolic effects in skeletal muscle, but the mechanisms are poorly understood. To test the hypothesis that leucine and insulin stimulate translation initiation in human skeletal muscle by phosphorylating 70-kDa ribosomal protein S6 kinase (p70S6k), we infused healthy adults with leucine alone ( n = 6), insulin alone ( n= 6), or both leucine and insulin ( n = 6) for 2 h. p70S6k and protein kinase B (PKB) serine473phosphorylation were measured in vastus lateralis muscles. Plasma leucine increased from ∼116 to 343 μmol/l during the leucine-alone and leucine + insulin infusions. Plasma insulin increased to ∼400 pmol/l during the insulin-alone and leucine + insulin infusions and was unchanged during the leucine-alone infusion. Phosphorylation of p70S6k increased 4-fold in response to leucine alone, 8-fold in response to insulin alone, and 18-fold after the leucine + insulin infusion. Insulin-alone and leucine + insulin infusions increased PKB phosphorylation, but leucine alone had no effect. These results show that physiological concentrations of leucine and insulin activate a key mediator of protein synthesis in human skeletal muscle. They suggest that leucine stimulates protein synthesis through a nutrient signaling mechanism independent of insulin, raising the possibility that administration of branched-chain amino acids may improve protein synthesis in insulin-resistant states.

Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle

1995 ◽  
Vol 268 (1) ◽  
pp. E75-E84 ◽  
Author(s):  
G. Biolo ◽  
R. Y. Fleming ◽  
S. P. Maggi ◽  
R. R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Human Skeletal Muscle ◽  
De Novo ◽  
Transmembrane Transport ◽  
Acid Transport ◽  
De Novo Synthesis ◽  
Intracellular Amino Acid

We have used stable isotopic tracers of amino acids to measure in vivo transmembrane transport of phenylalanine, leucine, lysine, alanine, and glutamine as well as the rates of intracellular amino acid appearance from proteolysis, de novo synthesis, and disappearance to protein synthesis in human skeletal muscle. Calculations were based on data obtained by the arteriovenous catheterization of the femoral vessels and muscle biopsy. We found that the fractional contribution of transport from the bloodstream to the total intracellular amino acid appearance depends on the individual amino acid, varying between 0.63 +/- 0.02 for phenylalanine and 0.22 +/- 0.02 for alanine. Rates of alanine and glutamine de novo synthesis were approximately eight and five times their rate of appearance from protein breakdown, respectively. The model-derived rate of protein synthesis was highly correlated with the same value calculated by means of the tracer incorporation technique. Furthermore, amino acid transport rates were in the range expected from literature values. Consequently, we conclude that our new model provides a valid means of quantifying the important aspects of protein synthesis, breakdown, and amino acid transport in human subjects.

scholarly journals Amino acids are necessary for the insulin-induced activation of mTOR/S6K1 signaling and protein synthesis in healthy and insulin resistant human skeletal muscle

2008 ◽  
Vol 27 (3) ◽  
pp. 447-456 ◽  
Author(s):  
Micah J. Drummond ◽  
Jill A. Bell ◽  
Satoshi Fujita ◽  
Hans C. Dreyer ◽  
Erin L. Glynn ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Human Skeletal Muscle ◽  
Insulin Resistant

Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise

2002 ◽  
Vol 93 (3) ◽  
pp. 1168-1180 ◽  
Author(s):  
Scot R. Kimball ◽  
Peter A. Farrell ◽  
Leonard S. Jefferson
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Translation Initiation ◽  
Translational Control ◽  
Initiation Factor ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Amino Acid Availability

Protein synthesis in skeletal muscle is modulated in response to a variety of stimuli. Two stimuli receiving a great deal of recent attention are increased amino acid availability and exercise. Both of these effectors stimulate protein synthesis in part through activation of translation initiation. However, the full response of translation initiation and protein synthesis to either effector is not observed in the absence of a minimal concentration of insulin. The combination of insulin and either increased amino acid availability or endurance exercise stimulates translation initiation and protein synthesis in part through activation of the ribosomal protein S6 protein kinase S6K1 as well as through enhanced association of eukaryotic initiation factor eIF4G with eIF4E, an event that promotes binding of mRNA to the ribosome. In contrast, insulin in combination with resistance exercise stimulates translation initiation and protein synthesis through enhanced activity of a guanine nucleotide exchange protein referred to as eIF2B. In both cases, the amount of insulin required for the effects is low, and a concentration of the hormone that approximates that observed in fasting animals is sufficient for maximal stimulation. This review summarizes the results of a number of recent studies that have helped to establish our present understanding of the interactions of insulin, amino acids, and exercise in the regulation of protein synthesis in skeletal muscle.

Role of Amino Acids and Peptides in the Molecular Signaling in Skeletal Muscle after Resistance Exercise

2007 ◽  
Vol 17 (s1) ◽  
pp. S47-S57 ◽  
Author(s):  
René Koopman
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Translation Initiation ◽  
Intracellular Signaling ◽  
Muscle Protein ◽  
Mrna Translation ◽  
Molecular Signaling ◽  
Stimulation Of

Resistance exercise can effectively result in an increase in muscle mass, or hypertrophy, which generally becomes apparent after several weeks of training. Muscle hypertrophy requires muscle protein synthesis to exceed protein breakdown during an extended time period. It has been firmly established that the interaction between exercise and nutrition (i.e., protein intake) is necessary to attain net protein accretion in skeletal muscle. The stimulation of protein synthesis is caused in part by stimulation of mRNA translation initiation. There is relatively little information on the response of intracellular signaling controlling mRNA translation to exercise and nutrition, especially in humans, but the available data in humans seem to suggest that a single bout of resistance exercise does not substantially enhance PI-3 kinase/mTOR signaling during the first 2 h after exercise. Moreover, it is demonstrated that the ingestion of protein or amino acids after exercise is crucial to further stimulate molecular signaling that controls translation initiation. The aim of this review is to provide an overview of the intracellular signaling related to translational control and to provide a summary of the current knowledge about the response of the signaling pathways controlling the anabolic response to exercise and nutrient intake in vivo in humans.

scholarly journals Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

2009 ◽  
Vol 106 (4) ◽  
pp. 1374-1384 ◽  
Author(s):  
Micah J. Drummond ◽  
Hans C. Dreyer ◽  
Christopher S. Fry ◽  
Erin L. Glynn ◽  
Blake B. Rasmussen
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Essential Amino Acids ◽  
Skeletal Muscle Protein ◽  
Mtorc1 Signaling

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

scholarly journals Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Humberto Nicastro ◽  
Claudia Ribeiro da Luz ◽  
Daniela Fojo Seixas Chaves ◽  
Luiz Roberto Grassmann Bechara ◽  
Vanessa Azevedo Voltarelli ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Protein Turnover ◽  
Protein Translation ◽  
Branched Chain Amino Acids ◽  
Inflammatory Status ◽  
Branched Chain ◽  
Muscle Remodeling

Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs), especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

Glucocorticoids modulate amino acid-induced translation initiation in human skeletal muscle

2004 ◽  
Vol 287 (2) ◽  
pp. E275-E281 ◽  
Author(s):  
Zhenqi Liu ◽  
Guolian Li ◽  
Scot R. Kimball ◽  
Linda A. Jahn ◽  
Eugene J. Barrett
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Amino Acid ◽  
Translation Initiation ◽  
Human Skeletal Muscle ◽  
Mrna Translation ◽  
Nucleotide Exchange ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Guanine Nucleotide Exchange

Amino acids are unique anabolic agents in that they nutritively signal to mRNA translation initiation and serve as substrates for protein synthesis in skeletal muscle. Glucocorticoid excess antagonizes the anabolic action of amino acids on protein synthesis in laboratory animals. To examine whether excessive glucocorticoids modulate mixed amino acid-signaled translation initiation in human skeletal muscle, we infused an amino acid mixture (10% Travasol) systemically to 16 young healthy male volunteers for 6 h in the absence ( n = 8) or presence ( n = 8) of glucocorticoid excess (dexamethasone 2 mg orally every 6 h for 3 days). Vastus lateralis muscles were biopsied before and after amino acid infusion, and the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1), ribosomal protein S6 kinase (p70S6K), and eIF2α and the guanine nucleotide exchange activity of eIF2B were measured. Systemic infusion of mixed amino acids significantly stimulated the phosphorylation of 4E-BP1 ( P < 0.04) and p70S6K ( P < 0.001) and the dephosphorylation of eIF2α ( P < 0.003) in the control group. Dexamethasone treatment did not alter the basal phosphorylation state of 4E-BP1, p70S6K, or eIF2α; however, it abrogated the stimulatory effect of amino acid infusion on the phosphorylation of 4E-BP1 ( P = 0.31) without affecting amino acid-induced phosphorylation of p70S6K ( P = 0.002) or dephosphorylation of eIF2α ( P = 0.003). Neither amino acid nor dexamethasone treatment altered the guanine nucleotide exchange activity of eIF2B. We conclude that changes of amino acid concentrations within the physiological range stimulate mRNA translation by enhancing the binding of mRNA to the 43S preinitiation complex, and the activity of p70S6K and glucocorticoid excess blocks the former action in vivo in human skeletal muscle.

scholarly journals Amino acid-induced stimulation of translation initiation in rat skeletal muscle

1999 ◽  
Vol 277 (6) ◽  
pp. E1077-E1086 ◽  
Author(s):  
Thomas C. Vary ◽  
Leonard S. Jefferson ◽  
Scot R. Kimball
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Translation Initiation ◽  
Amino Acid Supplementation ◽  
Initiation Factors ◽  
Eukaryotic Initiation Factors ◽  
Amino Acid Concentrations ◽  
Stimulation Of

Amino acids stimulate protein synthesis in skeletal muscle by accelerating translation initiation. In the two studies described herein, we examined mechanisms by which amino acids regulate translation initiation in perfused skeletal muscle hindlimb preparation of rats. In the first study, the effects of supraphysiological amino acid concentrations on eukaryotic initiation factors (eIF) 2B and 4E were compared with physiological concentrations of amino acids. Amino acid supplementation stimulated protein synthesis twofold. No changes were observed in eIF2B activity, in the amount of eIF4E associated with the eIF4E-binding protein (4E-BP1), or in the phosphorylation of 4E-BP1. The abundance of eIF4E bound to eIF4G and the extent of phosphorylation of eIF4E were increased by 800 and 20%, respectively. In the second study, we examined the effect of removing leucine on translation initiation when all other amino acids were maintained at supraphysiological concentrations. Removal of leucine from the perfusate decreased the rate of protein synthesis by 40%. The inhibition of protein synthesis was associated with a 40% decrease in eIF2B activity and an 80% fall in the abundance of eIF4E ⋅ eIF4G complex. The fall in eIF4G binding to eIF4E was associated with increased 4E-BP1 bound to eIF4E and a reduced phosphorylation of 4E-BP1. In contrast, the extent of phosphorylation of eIF4E was unaffected. We conclude that formation of the active eIF4E ⋅ eIF4G complex controls protein synthesis in skeletal muscle when the amino acid concentration is above the physiological range, whereas removal of leucine reduces protein synthesis through changes in both eIF2B and eIF4E.

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