Transport kinetics of amino acids across the resting human leg.

Lundholm, Kent; Bennegård, K.; Zachrisson, Helen; Lundgren, Fredrik; Edén, Elisabeth; Möller‐Loswick, Ann‐Charlotte

doi:10.1172/jci113132

Cited by 61 publications

(66 citation statements)

References 26 publications

(20 reference statements)

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“…In contrast, intravenous infusion by stepwise increased loads of amino acids to unselected patients and healthy volunteers indicated that amino acids themselves are involved in the process of initiation of translation (29), whereas carbohydrates and fat entirely lacked such effects (45). Also, there was no indication that glutamine alone had stimulatory effects in vivo in human muscles (46), while we observed that branched-chain amino acids stimulated human muscle protein synthesis, whereas insulin lacked this effect at physiological concentrations (32).…”

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confidence: 62%

Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques

Iresjö

Svanberg

Lundholm

2005

American Journal of Physiology-Endocrinology and Metabolism

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Iresjö, Britt-Marie, Elisabeth Svanberg, and Kent Lundholm. Reevaluation of amino acid stimulation of protein synthesis in murineand human-derived skeletal muscle cells assessed by independent techniques. Am J Physiol Endocrinol Metab 288: E1028 -E1037, 2005. First published December 14, 2004; doi:10.1152 doi:10. /ajpendo.00295.2004 and human rhabdomyosarcoma cells were cultured standardized in low (0.28 mM) and normal (9 mM) amino acid (AA) concentrations to reevaluate by independent methods to what extent AA activate initiation of protein synthesis. Methods used were incorporation of radioactive AA into proteins, distribution analysis of RNA in density gradient, and Western blots on initiation factors of translation of proteins in cultured cells as well as in vivo (gastrocnemius, C57Bl mice) during starvation/refeeding. Incorporation rate of AA gave incorrect results in a variety of conditions, where phenylalanine stimulated the incorporation rate of phenylalanine into proteins, but not of tyrosine, and tyrosine stimulated incorporation of tyrosine but not of phenylalanine. Similar problems were observed when [35 S]methionine was used for labeling of fractionated cellular proteins. However, the methods entirely independent of labeled AA incorporation indicated that essential AA activate initiation of translation, whereas nonessential AA did not. Branched-chain AA and glutamine, in combination with some other AA, also stimulated initiation of translation. Starvation/refeeding in vitro agreed qualitatively with results in vivo evaluated by initiation factors. Insulin at physiological concentrations (100 M/ml) did not stimulate global protein synthesis at low or normal AA concentrations but did so at supraphysiological levels (3 mU/ml), confirmed by independent methods. Our results reemphasize that labeled AA should be used with caution for quantification of protein synthesis, since the precursor pool(s) for protein synthesis is not in complete equilibrium with surrounding AA. "Flooding" tracee experiments did not overcome this problem. amino acids; insulin; initiation of translation; protein synthesis; muscle cells AROUND 45% OF THE BODY WEIGHT in adult humans is skeletal muscles, an important nitrogen reserve in different stress conditions such as trauma, infection, and starvation with balanced regulation of muscle protein synthesis and degradation to maintain muscle mass at functional levels (51). Feeding stimulates synthesis, whereas acute and chronic starvation will increase and decrease degradation, respectively (35). Mechanisms behind controlled protein balance in skeletal muscles over time have been extensively described in humans and animals based on studies in a variety of models from subcellular to cellular and tissue to organ levels (51). Yet, integrated signals behind protein balance in skeletal muscles are not fully understood, although several studies suggest amino acids in combination with hormones (insulin, IGF-I, and growth hormone) as key factors (1) communicated by intracellular phosphoprotein...

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confidence: 62%

Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques

Iresjö

Svanberg

Lundholm

2005

American Journal of Physiology-Endocrinology and Metabolism

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“…Taurine residence time in muscle was estimated at 427 h in healthy men, nine times that of glutamine (29). The low fractional turnover of taurine might account for the slow isotopic equilibration, as it took 4 h of a constant infusion of [ 13 C 2 ]taurine to reach isotopic equilibrium.…”

Section: Discussionmentioning

confidence: 99%

Taurine kinetics assessed using [1,2-¹³C₂]taurine in healthy adult humans

Rakotoambinina

Marks²,

Badran³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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Rakotoambinina, Benjamin, Lisa Marks, Abdul Monem Badran, Frank Igliki, François Thuillier, Pascal Crenn, Bernard Messing, and Dominique Darmaun. Taurine kinetics assessed using [1,2-13 C2]taurine in healthy adult humans. Am J Physiol Endocrinol Metab 287: E255-E262, 2004. First published March 9, 2004 10.1152/ajpendo.00333.2003.-To assess the dynamics of taurine metabolism in vivo, two sets of studies were carried out in healthy volunteers. First, pilot studies were carried in a single human subject to determine the time course of plasma and whole blood isotope enrichment over the course of an 8-h, unprimed continuous infusion of [1,2-13 C2]taurine. Second, five healthy adult males received two tracer infusions on separate days and in randomized order: 1) a 6-h continuous infusion of [1,2-13 C2]taurine (3.1 Ϯ 0.2 mol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) and 2) a bolus injection of [13 C2]taurine (3.0 Ϯ 0.1 mol/kg). Isotope enrichments in plasma and whole blood taurine were determined by gas chromatography-mass spectrometry. The pilot experiments allowed us to establish that steady-state isotope enrichment was reached in plasma and whole blood by the 5th h of tracer infusion. The plateau enrichment reached in whole blood was lower than that obtained in plasma taurine (P Ͻ 0.02). In the second set of studies, the appearance rate (Ra) of plasma taurine, determined from continuous infusion studies was 31.8 Ϯ 3.1 mol ⅐ kg Ϫ1 ⅐ h Ϫ1 . After a bolus injection of tracer, the enrichment decay over the subsequent 2 h was best fitted by a two-exponential curve. Taurine Ra was Ϸ85% higher when determined using the bolus injection technique compared with continuous infusion of tracer. We conclude that 1) taurine Ra into plasma is very low in healthy postabsorptive humans, and, due to taurine compartmentation between the extra-and intracellular milieus, may represent only interorgan taurine transfer and merely a small fraction of whole body taurine turnover; and 2) the bolus injection technique may overestimate taurine appearance into plasma. Further studies are warranted to determine whether alterations in bile taurine dynamics affect taurine Ra. constant infusion; bolus injection technique TAURINE (2-ETHANEAMINOSULFONIC ACID) IS, after glutamine, the second most abundant free amino acid in mammalian cells (2) and is involved in various physiological functions, including osmoregulation, defense against oxidative stress, detoxification of xenobiotics, membrane stabilization, retinal function, and bile conjugation (22). The two sources of body taurine are dietary intake and de novo taurine synthesis from methionine and cysteine, its sulfur amino acid precursors (22). Due to the limited taurine synthetic capacity of the newborn, taurine is considered a conditionally essential amino acid in infants (28). Taurine depletion has been described in adult patient populations as well (13, 50), as a result of either 1) increased utilization (11), 2) decreased intake (38), 3) decreased rate of de novo synthesis (45), or 4) various combinations of the thre...

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“…Because cataplerosis from TCA cycle is balanced with the inflow of carbon precursors (anaplerosis) (10), a higher glutamine flux would be expected in response to increased parenteral amino acid infusion. Lundholm and colleagues (23), in normal healthy adults, also showed an increased DGln across the leg in response to infusion of a balanced amino acid solution. A similar observation was made by Abumrad and colleagues (24) across forearm skeletal muscle during intravenous amino acid infusion.…”

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confidence: 88%

“…Although the above suggests skeletal muscle to be the major site for glutamine synthesis during amino acid infusion, it is not likely to be the predominant contributor. Studies in human adults show that only 25-30% of infused amino acid nitrogen is taken up by the skeletal muscle and 70% is removed by the splanchnic compartment (23,27,28). Thus, it is likely that the observed increase in Ra of glutamine in response to increased amino acid infusion is contributed by both the skeletal muscle as well as by the splanchnic organs.…”

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confidence: 99%

Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants

et al. 2005

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Glutamine has been proposed to be conditionally essential for premature infants, and the currently used parenteral nutrient mixtures do not contain glutamine. De novo glutamine synthesis (DGln) is linked to inflow of carbon into and out of the tricarboxylic acid (TCA) cycle. We hypothesized that a higher supply of parenteral amino acids by increasing the influx of amino acid carbon into the TCA cycle will enhance the rate of DGln. Very low birth weight infants were randomized to receive parenteral amino acids either 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5 h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics were examined using [5][6][7][8][9][10][11][12][13][14][15] 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase in DGln, leucine transamination, and urea synthesis, but had no effect on Ra phenylalanine (AA-Ext). These data show an acute increase in parenteral amino acid-suppressed proteolysis, however, such an effect was not seen when amino acids were infused for 20 h and resulted in an increase in glutamine synthesis. Glutamine participates in a number of key metabolic processes (1) and is also proposed to play an important role in enhancing immune function (2-4). A decrease in plasma glutamine concentration in response to stress (acute illness, burns, trauma, etc.) suggests that the rate of DGln is unable to keep pace with the rate of utilization/requirement. This has led several investigators to suggest that glutamine is a conditionally essential amino acid. Studies in adults show that parenteral nutrition supplemented with glutamine decreased both the morbidity and mortality (5,6).Because the concentration of plasma glutamine is lower in VLBW infants, and the currently used parenteral nutrient solutions do not contain glutamine, VLBW premature infants were identified as another group of subjects who could potentially benefit from supplementation of enteral and parenteral nutrition with glutamine (7-9). However, whether provision of a higher amount of parenteral amino acids to these VLBW infants enhances the rate of DGln has not been examined.Glutamine is synthesized by transamination of ␣-ketoglutarate to glutamate and conversion of glutamate to glutamine. The latter reaction is catalyzed by glutamine synthase. The sources of carbon skeleton for the synthesis of glutamine, i.e. glutamate and ␣-ketoglutarate, are derived from the amino acids entering the TCA cycle (anaplerosis). An increase influx of these amino acids would be anticipated to result in an increase in DGln (cataplerosis) (10). Studies in human adults show that supplementation of parenteral nutrition with analogues of ␣-ketoglutarate enhances the intracellular pool of glutamine in the muscle (11,12). We have previously shown that th...

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Transport kinetics of amino acids across the resting human leg.

Cited by 61 publications

References 26 publications

Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques

Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques

Taurine kinetics assessed using [1,2-¹³C₂]taurine in healthy adult humans

Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants

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Transport kinetics of amino acids across the resting human leg.

Cited by 61 publications

References 26 publications

Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques

Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques

Taurine kinetics assessed using [1,2-13C2]taurine in healthy adult humans

Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants

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Taurine kinetics assessed using [1,2-¹³C₂]taurine in healthy adult humans