Regulative capacity of glutamine

Oehler, Rudolf; Roth, Erich

doi:10.1097/01.mco.0000068962.34812.ac

Cited by 47 publications

(33 citation statements)

References 51 publications

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“…During the septic state, increased glutamine production in skeletal muscle is likely very important, because plasma glutamine is an important energy as well as nitrogen source for some immune cells (18). Thus, because the BCAAs contribute to glutamine production in skeletal muscle (3,4,19), these amino acids also play important roles during sepsis.…”

Section: Effects Of Lps Treatment On the Dynamics Of Plasma Free Bcaamentioning

confidence: 99%

The Effects of Endotoxin on Plasma Free Amino Acid Concentrations in Rats

Asai

Bajotto

Yoshizato

et al. 2008

J Nutr Sci Vitaminol

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SummaryWe examined the effects of lipopolysaccharide (LPS) injection on body temperature and plasma free amino acid concentrations in rats. A catheter was placed in the jugular vein of the rats in order to draw blood from and to inject LPS into awake animals. On the day of the experiment, body temperature was recorded during the experiment (330 min) and blood was drawn before and at several time points after injection of LPS (10 g/kg body weight). Body temperature in LPS-treated rats began to rise ~30 min after injection with a peak at 120 min, and afterward remained ~1˚C higher than that in control rats through the end of the experiment. Concentrations of many plasma free amino acids were decreased by LPS treatment, with a nadir at ~120 min, and then were increased to the level of or over the control. It appears that thermoregulatory responses induced by LPS treatment may be related to alterations in plasma free amino acid concentrations. Effects of LPS treatment on the dynamics of plasma free branched-chain amino acid (BCAA) concentrations in rats with peroral or intravenous administration of BCAAs were also examined. The results showed that the rise in plasma BCAA concentrations after peroral BCAA administration was significantly suppressed by LPS treatment, but the dynamics of plasma BCAAs after intravenous administration was not affected by LPS, suggesting that LPS treatment inhibited the intestinal absorption of BCAAs into the circulation. These results suggest that the availability of administered BCAAs to the body tissues during sepsis is higher following parenteral than peroral administration. Key Words endotoxin, lipopolysaccharide, plasma amino acids, branched-chain amino acids (BCAA), body temperature Sepsis induces several metabolic responses including negative nitrogen balance and loss of lean body mass. This catabolic phase is associated with muscle protein breakdown ( 1 , 2 ) and increased whole body amino acid metabolism ( 3 ). Glutamine metabolism and branchedchain amino acid (BCAA) catabolism are especially prominent; glutamine production is increased through proteolysis and BCAAs are actively oxidized in skeletal muscles during sepsis ( 4 , 5 ). Therefore, administration of these amino acids is considered to have a potential to alleviate the septic conditions ( 6 , 7 ).Administration of bacterial lipopolysaccharide (LPS) preparations to laboratory animals is widely used to reproduce the septic state, in which various metabolic as well as thermoregulatory responses are induced in association with systemic inflammation. It has been reported that the thermoregulatory response to LPS administration is dependent upon the dose of LPS and ambient temperature ( 8 ). In many studies ( 5 , 9 -12 ), high, shock-inducing doses such as 500 g LPS/kg body weight (BW) or more have been used and these doses caused pronounced hypothermia ( 8 ). On the other hand, it has been reported that intravenous administration of low or intermediary doses (less than 10 g/kg BW) of LPS elicits fever when animals are kept i...

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Section: Effects Of Lps Treatment On the Dynamics Of Plasma Free Bcaamentioning

confidence: 99%

The Effects of Endotoxin on Plasma Free Amino Acid Concentrations in Rats

Asai

Bajotto

Yoshizato

et al. 2008

J Nutr Sci Vitaminol

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“…Consequently, l-Gln has been proposed as a key factor in growth and maintenance of mammalian tissues (14), and l-Gln availability and losses from muscle may be important contributors to wasting illness and clinical outcome in seriously ill patients (15). A crucial factor is active transport of l-Gln across the plasma membrane (15), maintaining an intracellular concentration at least 20 times higher than the 0.5 to 1 mM found in extracellular fluid (16).…”

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confidence: 99%

Acidosis-Sensing Glutamine Pump SNAT2 Determines Amino Acid Levels and Mammalian Target of Rapamycin Signalling to Protein Synthesis in L6 Muscle Cells

Evans¹,

Nasim²,

Brown³

et al. 2007

Journal of the American Society of Nephrology

104

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Wasting of lean tissue as a consequence of metabolic acidosis is a serious problem in patients with chronic renal failure. A possible contributor is inhibition by low pH of the System A (SNAT2) transporter, which carries the amino acid L-glutamine (L-Gln) into muscle cells. The aim of this study was to determine the effect of selective SNAT2 inhibition on intracellular amino acid profiles and amino acid-dependent signaling through mammalian target of rapamycin in L6 skeletal muscle cells. Inhibition of SNAT2 with the selective competitive substrate methylaminoisobutyrate, metabolic acidosis (pH 7.1), or silencing SNAT2 expression with small interfering RNA all depleted intracellular L-Gln. SNAT2 inhibition also indirectly depleted other amino acids whose intracellular concentrations are maintained by the L-Gln gradient across the plasma membrane, notably the anabolic amino acid L-leucine. Consequently, SNAT2 inhibition strongly impaired signaling through mammalian target of rapamycin to ribosomal protein S6 kinase, ribosomal protein S6, and 4E-BP1, leading to impairment of protein synthesis comparable with that induced by rapamycin. It is concluded that even though SNAT2 is only one of several L-Gln transporters in muscle, it may determine intracellular anabolic amino acid levels, regulating the amino acid signaling that affects protein mass, nucleotide/nucleic acid metabolism, and cell growth.

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“…Glutamine is the most abundant amino acid in blood with a concentration of 0.6 mM/l, which is higher than any other amino acid [12,13]. Glutamine is known to be one of the main sources of energy for the intestinal epithelium by generating adenosine 5′-triphosphate (ATP).…”

Section: Introductionmentioning

confidence: 99%

“…Glutamine is known to be one of the main sources of energy for the intestinal epithelium by generating adenosine 5′-triphosphate (ATP). It is also the precursor of many other amino acids such as proline, arginine, citruline, and alanine, which play an important coadjuvant role during gut healing [13,14]. The intestinal uptake of glutamine is enhanced when the body is subjected to stressful conditions, such as chemotherapy challenge [15,16].…”

Section: Introductionmentioning

confidence: 99%

Alanyl-Glutamine and Glutamine Supplementation Improves 5-Fluorouracil-Induced Intestinal Epithelium Damage In Vitro

et al. 2008

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In this study, we have examined the role of glutamine derivatives in reducing 5-fluorouracil (5-FU)-induced epithelial damage in an undifferentiated crypt intestinal cell line, IEC-6. In this model, we have investigated proliferation indirectly by detecting the enzyme-derived formazan dye from the tetrazolium salt WST-1 in viable cells at 24 and 48 h after 5-FU treatment. Migration was measured at 12 and 24 h after razor scraping of the cell monolayer. Cell death was measured by quantifying the percentage of apoptotic and necrotic figures by flow cytometry at 12 and 24 h following 5-FU challenge. Neither glutamine nor alanyl-glutamine prevented 5-FU-induced apoptosis and necrosis in IEC-6 cells at 12 and 24 h after 5-FU challenge. However, glutamine and alanyl-glutamine enhanced migration and proliferation when compared with 5-FU-treated controls (P <0.05). These new findings support our earlier study on the benefit of oral glutamine in enhancing epithelial recovery after 5-FU challenge.

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Regulative capacity of glutamine

Abstract: These data show that glutamine-utilizing cells possess molecular mechanisms to detect the availability of glutamine and to respond specifically to changes in the extracellular glutamine concentration.

Cited by 47 publications

References 51 publications

The Effects of Endotoxin on Plasma Free Amino Acid Concentrations in Rats

The Effects of Endotoxin on Plasma Free Amino Acid Concentrations in Rats

Acidosis-Sensing Glutamine Pump SNAT2 Determines Amino Acid Levels and Mammalian Target of Rapamycin Signalling to Protein Synthesis in L6 Muscle Cells

Alanyl-Glutamine and Glutamine Supplementation Improves 5-Fluorouracil-Induced Intestinal Epithelium Damage In Vitro

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