Muscle and splanchnic glutamine and glutamate metabolism in postabsorptive and starved man

Eb, Marliss; Aoki, Thomas T.; Pozefsky, Thomas; Most, Albert S.; Cahill, George F.

doi:10.1172/jci106552

Cited by 264 publications

(90 citation statements)

References 21 publications

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“…Splanchnic uptake of glutamine from plasma has recently been shown to be comparable to that of alanine (11). However, whereas blood cells add substantially to the total splanchnic uptake of alanine, they do not have a similar role with regard to splanchnic extraction of glutamine (Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…Individual acidic and neutral amino acids were determined by the automated ionexchange chromatographic technique (10) on a Beckman model 120C amino-acid analyzer (Beckman Instrument Co., Palo Alto, Calif.). By this technique, glutamine and asparagine emerge as a single peak, and are referred to collectively as glutamine, since inter-organ exchange of asparagine is negligible (11). Glutamate values on the other hand are often artifactually elevated with the chromatographic technique (12) and consequently are not reported.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Evidence of Inter-organ Amino-Acid Transport by Blood Cells in Humans

Felig

Wahren²,

Räf

1973

Proc. Natl. Acad. Sci. U.S.A.

211

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To evaluate the contribution of blood cellular elements to inter-organ transport of amino acids, net exchange across the leg and splanchnic bed of 17 amino acids was determined in seven healthy postabsorptive subjects by use of both whole blood and plasma for analysis. Arterial-portal venous differences were measured in five additional subjects undergoing elective cholecystectomy. By use of whole blood, significant net release of amino acids was noted from the leg and gut, while a consistent uptake was observed by the splanchnic bed. The output of alanine from the leg and gut and the uptake of this amino acid by the splanchnic bed exceeded that of all other amino acids and accounted for 35-40% of total amino-acid exchange. Transport by way of plasma could not account for total tissue release or uptake of alanine, threonine, serine, glutamine, methionine, leucine, isoleucine, tyrosine, and citrulline. For each of these amino acids, significant tissue exchange was calculated to occur by way of the blood cellular elements, the direction of which generally paralleled the net shifts occurring in plasma. For alanine, 30% of its output from the leg and gut and 22% of its uptake by the splanchnic area occurred by way of blood cells. We conclude that the blood cellular elements, presumably erythrocytes, contribute substantially to the net flux of amino acids from muscle and gut to liver in normal postabsorptive humans. Alanine predominates in the inter-organ transfer of amino acids occurring by way of blood cells as well as plasma.It is generally believed that plasma rather than erythrocytes is the vehicle of amino-acid exchange between tissues (1). The slow equilibration time of amino-acid transport across erythrocyte membranes, as indicated by in vitro studies (2), has led to the widely held notion that erythrocytes are of little, if any, significance in the inter-organ transfer of amino acids. As a consequence, studies of amino-acid metabolism in physiologic as well as pathologic circumstances have generally been restricted to measurements of amino-acid concentrations in plasma rather than whole blood (1, 3). However, recent observations on glutamate flux in intact humans suggest a dynamic role for erythrocytes in the transport of this amino acid across muscle tissue (4). In addition, studies in dogs indicate that erythrocytes and plasma may play independent and occasionally opposing roles in the exchange of several amino acids across the liver and gut (5, 6). The present investigation was consequently undertaken to determine the contribution of blood cells, primarily erythrocytes, to inter-organ amino-acid transport in normal humans. This was done by examination of peripheral, splanchnic, and portal exchange of 17 individual amino acids in the postabsorptive state; whole blood as well as plasma was used for the determination of arterio-venous differences. In particular, we were interested in the contribution of the blood cellular elements to the tissue exchange of alanine. Plasma analyses have emphasized the ...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Evidence of Inter-organ Amino-Acid Transport by Blood Cells in Humans

Felig

Wahren²,

Räf

1973

Proc. Natl. Acad. Sci. U.S.A.

211

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“…As it contains in its structure two nitrogen groups that can be mobilized, Gln may be a vehicle for tissue nitrogen exchange, and may play an essential role in several important metabolic pathways (Marliss et al, 1971;Smith, 1990).…”

Section: Glutamine Action On the Immune Responsementioning

confidence: 99%

Influence of glutamine and vitamin E on the performance and the immune responses of broiler chickens

Sakamoto

Murakami

Silveira

et al. 2006

Rev. Bras. Cienc. Avic.

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This study aimed at evaluating the influence of Glutamine (Gln) and Vitamin E (VE) supplementation on the performance and immune response of broilers. A completely randomizes experimental design with a 2 x 3 (VE x Gln) factorial arrangement was used. VE was supplemented at 10 and 500 mg/kg feed, with or without Gln (1%) addition, and two periods of supplementation in the starter diets (1-7 and 1-14 days of age), with five replicates of 50 birds each. The analyzed parameters were: live performance (weight gain, feed intake, and feed conversion ratio); relative weights of the spleen, bursa, and thymus; antibody titers (with sheep red blood cells suspension -SRBC) and cutaneous basophilic hypersensivity (CBH). Data were submitted to the analysis of variance, and means were compared using the test of Tukey. Treatments did not influence (P>0.05) live performance parameters or antibody titers. VE reduced (P=0.01) CBH, with the level of 10 mg VE/kg allowing higher cell proliferation as compared to 500 mg VE/kg. As to lymphoid organs, only the spleen was affected (P=0.035) by Gln, which resulted in higher spleen relative weight when fed during the first week of age. Results showed that 10 mg VE/kg with Gln (1-7 days) promoted better immune responses.

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“…Furthermore, glutamine tracer also enters the intracellular pools of all other organs and is used for protein synthesis in all organs of the body. Liver and the splanchnic bed extract glutamine very efficiently, as they have high glutaminase (EC 3.5.1.2) activities and a high oxidative capacity for glutamine (Marliss et al 1971;Matthews et al 1993). Thus, the enrichment measured by Biolo et al (1995a), particularly that in the 5 h biopsy samples, seems a gross overestimation.…”

Section: Three-compartment Modelmentioning

confidence: 99%

Tracers to investigate protein and amino acid metabolism in human subjects

Wagenmakers

1999

Proc. Nutr. Soc.

110

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Abbreviations: FSR, fractional synthesis rate; IRMS, isotope-ratio mass spectrometry; α-KIC, α-ketoisocaproic acid; MS, mass spectrometry; nb, net balance of tracer; NB, net balance of tracee; Ra, rate of appearance; Rd, rate of disappearance. The contribution of whole-body methods to the future gain of knowledge is expected to be limited due to the fact that most physiological disturbances have been investigated extensively, and due to the lack of information on the relative contribution of various tissues and proteins to whole-body changes.Tracer amino acid-incorporation methods are most suited to investigate these latter aspects of protein metabolism. These methods have shown that some tissues (liver and gut) have much higher turnover rates and deposit much more protein than others (muscle). Massive differences also exist between the fractional synthesis rates of individual proteins. The incorporation methods have been properly validated, although minor disagreements remain on the identity of the true precursor pool (the enrichment of which should be used in the calculations). Arterio-venous organ balance studies have shown that little protein is deposited in skeletal muscle following a proteincontaining meal, while much more protein is deposited in liver and gut. The amount deposited in the feeding period in each of these tissues is released again during overnight fasting. The addition of tracers to organ balance studies allows the simultaneous estimation of protein synthesis and protein breakdown, and provides information on whether changes in net protein balance are caused primarily by a change in protein synthesis or in protein breakdown. In the case of a small arterio-venous difference in a tissue with a high blood flow, estimates of protein synthesis and breakdown become very uncertain, limiting the value of using the tracer. An additional measurement of the intracellular free amino acid pool enrichment allows a correction for amino acid recycling and quantification of the inward and outward transmembrane transport. However, in order to obtain reliable estimates of the intramuscular amino acid enrichment and, therefore, of muscle protein synthesis and breakdown in this so-called three-pool model, the muscle should be freeze-dried and the resulting fibres should be freed from connective tissue and small blood clots under a dissection microscope. Even when optimal precautions are taken, the calculations in these tracer balance methods use multiple variables and, therefore, are bound to lead to more variability in estimates of protein synthesis than the tracer amino acid incorporation methods. In the future, most studies should focus on the measurement of protein synthesis and breakdown in specific proteins in order to understand the mechanisms behind tissue adaptation in response to various stimuli (feeding, fasting, exercise, trauma, sepsis, disuse and disease). The tracer laboratories, therefore, should improve the methodology to allow the measurement of low tracer amino acid enrichments in small amount...

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Muscle and splanchnic glutamine and glutamate metabolism in postabsorptive and starved man

Cited by 264 publications

References 21 publications

Evidence of Inter-organ Amino-Acid Transport by Blood Cells in Humans

Evidence of Inter-organ Amino-Acid Transport by Blood Cells in Humans

Influence of glutamine and vitamin E on the performance and the immune responses of broiler chickens

Tracers to investigate protein and amino acid metabolism in human subjects

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