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PubMed2000

Phorbol esters rapidly attenuate glutamine uptake and growth in human colon carcinoma cells.

BACKGROUND: The amino acid glutamine, while essential for gut epithelial growth, has also been shown to stimulate colon carcinoma proliferation and diminish differentiation. Human colon carcinomas are known to extract and metabolize glutamine at rates severalfold greater than those of normal tissues, but the regulation of this response is unclear. Previously we reported that phorbol esters regulate hepatoma System ASC/B(0)-mediated glutamine uptake and cell growth. As human colon carcinoma cells use this same transporter for glutamine uptake, the present studies were undertaken to determine whether similar regulation functions in colon carcinoma. MATERIALS AND METHODS: Human colon carcinoma cell lines (WiDr and HT29) were treated with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and initial-rate transport of glutamine and other nutrients was measured at specific times thereafter. Growth rates were monitored during culture +/- PMA or an excess of System ASC/B(0) substrates relative to glutamine. RESULTS: PMA treatment induced a rapid inhibition of glutamine uptake rates in WiDr and HT29 cells by 30 and 57%, respectively, after 1 h. Cycloheximide failed to block this response, indicating that the mechanism by which PMA exerts its effects is posttranslational. The inhibition of glutamine uptake by PMA was abrogated by the PKC inhibitor staurosporine, suggesting that this rapid System ASC/B(0) regulation may be mediated by a PKC-dependent pathway. PMA also significantly decreased transport via System y(+) (arginine) and System A (small zwitterionic amino acids). Chronic phorbol ester treatment inhibited WiDr cell growth, as did attenuation of System B(0)-mediated glutamine uptake with other transporter substrates. CONCLUSIONS: System ASC/B(0) uptake governs glutamine-dependent growth in colon carcinoma cell lines, and is regulated by a phorbol ester-sensitive pathway that may involve PKC. The results further establish the link between glutamine uptake and colon carcinoma cell growth, a relationship worthy of further investigation with the goal of discovering novel cancer therapeutic targets.

Arginine↗
PubMed1995

Glutamine metabolism in AS-30D hepatoma cells. Evidence for its conversion into lipids via reductive carboxylation.

A study was undertaken to assess the role of a physiological concentration of glutamine in AS-30D cell metabolism. Flux of 14C-glutamine to 14CO2 and of 14C-acetate to glutamate was detected indicating reversible flux between glutamate and TCA cycle alpha-ketoglutarate. These fluxes were transaminase dependent. A flux analysis was compared using data from three tracers that label alpha-ketoglutarate carbon 5, [2-14C]glucose, [1-14C]acetate and [5-14C]glutamine. The analysis indicated that the probability of flux of TCA cycle alpha-ketoglutarate to glutamate was, at minimum, only slightly less than the probability of flux of alpha-ketoglutarate through alpha-ketoglutarate dehydrogenase. The apparent Km for oxidative flux of [14C]glutamine to 14CO2, 0.07 mM, indicated that this flux was at a maximal rate at physiological, 0.75 mM, glutamine. Although oxidative flux through alpha-ketoglutrate dehydrogenase was the major fate of glutamine, flux of glutamine to lipid via reductive carboxylation of alpha-ketoglutarate was demonstrated by measuring incorporation of [5-14C]glutamine into 14C-lipid. In media containing glucose (6 mM), and glutamine (0.75 mM) 47 per cent of the lipid synthesized from substrates in the media was derived from glutamine via reductive carboxylation and 49 per cent from glucose. These findings of nearly equal fluxes suggest that lipogenesis via reductive carboxylation may be an important role of glutamine in hepatoma cells.

Animals↗
PubMed2000

Bidirectional supply of glutamine maintains enterocyte ATP content in the in vitro using chamber model.

Glutamine is the principal energy source for enterocytes, but it is not known whether parenteral or enteral supplementation is most beneficial to gut integrity. The aim of this study was to evaluate the effects of glutamine in uni- or bidirectional supply on the viability of intestinal mucosa of starved rats during incubation in Ussing chambers. Segments of jejunum from rats starved for 48 h were randomly mounted in Ussing chambers with three nutrient solutions: Krebs buffer without glutamine; 6 mM glutamine added to the mucosal side; 6 mM glutamine added to the mucosal side and 0.6 mM glutamine to the serosal side. ATP content of the mucosa, electrophysiology, and 51Cr-ethylenediaminetetraacetate (EDTA) permeability were studied during 180 min of incubation. The addition of glutamine to both sides of the stripped mucosa improved ATP levels compared to the Krebs solution (P < 0.05), and the addition of glutamine resulted in an increase in short circuit current (P < 0.05). No significant differences were seen in 51Cr-EDTA permeability or epithelial electrical resistance. Glutamine supplementation to both the luminal and serosal side in the Ussing chamber was more effective than luminal glutamine only in maintaining ATP levels of intestinal mucosa. Bidirectional supplementation of glutamine might improve intestinal energy metabolism and viability in in vitro studies.

Adenosine Triphosphate↗
PubMed1999

Is glutamine essential for the maintenance of intestinal function? A study in the isolated perfused rat small intestine.

Glutamine has received considerable interest as a gut-targeted nutrient due to its proposed key role in the maintenance of intestinal structure and function. We used a preparation of isolated vascularly perfused rat small intestine to investigate whether glutamine is essential for the maintenance of intestinal function. When glutamine was available, arterial glutamine was extracted at 15 +/- 2%, and net uptake was -89 +/- 5 nmol min-1 g-1. Nitrogenous metabolites ammonia, alanine, and citrulline (41 +/- 7, 41 +/- 4, and 11 +/- 2 nmol min-1 g-1, respectively) were released into the venous perfusate, but only ammonia was also excreted into the lumen (36 +/- 3 nmol min-1 g-1). In the absence of exogenous glutamine alanine release was halved and that of citrulline and ammonia nullified. Additional inhibition of glutamine synthetase yielded the same results. In all cases variables of tissue function were fully maintained also in the absence of exogenous and/or endogenous glutamine. The inhibition of glutaminase/amidotransferase reactions, however, was accompanied by a reduction in glutamine consumption and a graded deterioration in tissue function. In conclusion, glutamine seems to be dispensable as a metabolic fuel to be fully oxidized by the mucosa. However, the inhibition of major glutamine consuming pathways was associated with impaired tissue function and viability. Therefore the role of intestinal glutamine metabolism seems to be threefold: (a) providing affluent amounts of nitrogen precursors for mucosal anabolic pathways to maintain intestinal structure and function, (b) feeding the liver with an optimal substrate mix, and (c) providing citrulline and thereby arginine for the whole organism.

Alanine↗
PubMed1998

Competitive sustained exercise in humans, lymphokine activated killer cell activity, and glutamine--an intervention study.

This study examined whether oral glutamine supplementation abolishes some of the exercise-induced changes in lymphocyte functions following long-term intense exercise. A group of 16 marathon runners participating in The Copenhagen Marathon 1996 were placed randomly in either a placebo (n = 7) or a glutamine receiving group (n = 9). Each subject received four doses of either placebo or glutamine (100 mg x kg(-1)) administered at 0, 30, 60, and 90-min post-race. In the placebo group the plasma glutamine concentrations were lower than pre-race values during the post-exercise period [mean 647 (SEM 32) compared to 470 (SEM 22) micromol x 1(-1) 90-min post-race, P < 0.05] whereas glutamine supplementation maintained the plasma glutamine concentration (at approximately 750 micromol x 1(-1)). Glutamine supplementation in vivo had no effect on the lymphokine activated killer (LAK) cell activity, the proliferative responses or the exercise-induced changes in concentrations or percentages of any of the leucocyte subpopulations examined. Glutamine addition in in vitro studies enhanced the proliferative response in both groups. These data would suggest that decreased plasma glutamine concentrations post-exercise are not responsible for exercise-induced decrease in LAK activity and that the influence of glutamine in vitro is not dependent on the plasma glutamine concentration at the time of sampling.

Adult↗
PubMed2002

Gut glutamine metabolism at different stages of sepsis in rats.

PURPOSE: To investigate gut glutamine metabolism and determine the effects of glutamine supplementation in different stages of sepsis in a rat model. METHODS: Sepsis was induced by cecal ligation and puncture (CLP), and control rats underwent a sham operation. In the first experiment, a continuous infusion of normal saline was started at the end of the operation. Intestinal blood flow, glutamine concentrations of the abdominal aorta and superior mesenteric vein (SMV) were measured, and gut glutamine extraction and flux were calculated 5 h after the sham operation, and 5 and 20 h after CLP, being groups Ia ( n = 9), Ib ( n = 8), and Ic ( n = 8), respectively. In the second experiment, animals received a continuous infusion of alanyl-glutamine instead of normal saline and were divided into groups IIa ( n = 8), IIb ( n = 8), and IIc ( n = 6). The same parameters were measured in each group and compared with those of the corresponding group in the first experiment. RESULTS: In the first experiment, no significant difference in SMV blood flow was seen among the groups. The arterial glutamine concentration was increased in group Ic ( P < 0.05) compared with that in groups Ia and Ib. Gut glutamine extraction was significantly increased in group Ib ( P < 0.01) and significantly decreased in group Ic ( P < 0.05) compared with that in group Ia. In the second experiment, gut glutamine flux was significantly increased in group Ilb ( P < 0.01) compared with that in group Ib, but the increase did not reach statistical significance between groups Ia and IIa or between groups Ic and IIc. CONCLUSION: These results indicate that intestinal glutamine uptake is increased and glutamine utilization is enhanced by glutamine supplementation in early sepsis.

Animals↗
PubMed2006

Free glutamine as a major precursor of brown products and fluorophores in Maillard reaction systems.

Glutamine is one of the most abundant free amino acid found in raw food. In this study, the contribution of free glutamine to nonenzymatic browning and fluorescence was investigated using an aqueous model system with methylglyoxal. The results indicated that glutamine contributed to the Maillard reaction via two pathways. First, the hydrolysis of the amide bond of glutamine led to the release of ammonia which was implicated in the formation of brown color and fluorescence. Among other nitrogen donors tested (asparagine, glutamic acid and urea) our results demonstrated that free glutamine was a major source of ammonia during heating. When heated at 120 and 180 degrees C, 100% of ammonia was released from glutamine after 60 and 10 min, respectively. The second pathway involved a direct Maillard reaction with the alpha-amino group of glutamine. Both pathways led to a rapid and complete destruction of glutamine when heated in the model systems. With reference to the Maillard browning (absorbance at 420 nm) glutamine turned out to be the most reactive amine, followed by asparagine, glutamate, ammonia and urea. Maximum fluorescence (excitation and emission wavelengths at 330 and 450 nm, respectively) was also observed with glutamine followed by urea and ammonia. Overall this study suggested that free glutamine predominantly contributes to the color and fluorescence formations of foodstuffs.

Glutamine↗
PubMed1988

Multiple mechanisms by which glutamine synthetase levels are controlled in murine tissue culture cells.

We report the isolation of a complimentary DNA (cDNA) clone encoding glutamine synthetase, derived from a population of methionine sulfoxime-resistant mouse GF1 fibroblasts. When GF1 cells are incubated for 48 h in the presence of the glucocorticoid hormone dexamethasone, the specific activity of glutamine synthetase (GS), assayed as glutamyltransferase activity, increases by threefold. Based on dot hybridization analysis, hormonal treatment also produces a similar increase in the level of GS mRNA. When GF1 cells or mouse Neuro 2A neuroblastoma cells are transferred from medium containing 4 mM glutamine to glutamine-free medium, glutamyltransferase activity increases by at least fivefold. However, the presence or absence or glutamine in the medium does not affect the relative level of glutamine synthetase mRNA in either cell line. With both GF1 and Neuro 2A cells, the half-time for the decline in glutamine synthetase enzyme activity on addition of glutamine to the medium is approximately 1.5 h. This rapid decline, coupled with the lack of effect of glutamine on the level of GS messenger RNA in Neuro 2A cells, renders it unlikely that neural cells alter glutamine synthetase levels in response to glutamine by a biosynthetic mechanism, as suggested by previous authors [L. Lacoste, K.D. Chaudhary, and J. Lapointe (1982) J. Neurochem. 39, 78-85].

Animals↗
PubMed1989

Transport of glutamine in rat intestinal brush-border membrane vesicles.

Transport of glutamine across the brush-border membrane of the rat intestine was examined using brush-border membrane vesicle (BBMV) technique. Osmolarity and temperature studies indicated that the uptake of glutamine by BBMV is mostly the result of transport of the substrate into the intravesicular space. Transport of glutamine was Na+-gradient dependent (out greater than in) with a distinct 'overshoot' phenomenon. Initial rate of transport of glutamine as a function of concentration was saturable both in the presence and absence of a Na+ gradient (out greater than in). Apparent Km of 3.50 and 3.34 mM and Vmax of 707 and 282 pmol/mg protein per 7 s, were calculated for the Na+-dependent and the Na+-independent transport processes of glutamine. The transport of [3H]glutamine by the Na+-dependent and the Na+-independent processes was severely inhibited by the addition to the incubation medium of other amino acids and unlabelled glutamine. Inducing a relatively negative intravesicular compartment with the use of valinomycin and an outwardly directed K+ gradient stimulated glutamine transport. This indicates that transport of the substrate by the Na+-dependent process is electrogenic in nature. Transport of glutamine by the Na+-independent process, however, appeared to be electroneutral in nature. These results demonstrate the existence of two carrier-mediated transport processes for glutamine in the rat intestinal BBMV, one is Na+-dependent and the other is Na+-independent. Furthermore, the results suggest that glutamine transport by the Na+-dependent process probably occurs by a glutamine/Na+ cotransport mechanism.

Animals↗
PubMed1986

Effect of metabolic acidosis on hindquarter glutamine and alanine release.

The relationship between hindquarter glutamine release and renal glutamine extraction was studied in rats undergoing chronic metabolic acidosis. Metabolic acidosis was induced by maintaining rats on NH4CL for four days; controls were pair-fed NH4HCO3. Metabolic acidosis increased renal glutamine extraction 8-fold and decreased arterial plasma glutamine concentration 40%. Hindquarter glutamine release rose 5-fold in acidosis due to an increased arteriovenous glutamine concentration difference and a significant rise in blood flow through the hindquarters. Both ammonia and glutamate extraction in the hindquarter increased in acidosis and could account for 25% of the glutamine nitrogen released. Alanine release by hindquarters, which exceeded glutamine release in the control animals, was greatly depressed in metabolic acidosis. The reduction in alanine nitrogen release during acidosis could account for 25% of the glutamine nitrogen released. Consequently, metabolic acidosis stimulates hindquarter glutamine release at the expense of alanine and is also supported by greater extraction of ammonia and glutamate. However, other N sources must supply nearly 50% of the glutamine nitrogen released based on balance studies.

Acidosis↗
PubMed1992

Partial enterectomy in the rat does not diminish muscle glutamine production.

The hypothesis was posed that consumption of the amino acid glutamine by the splanchnic tissues is an important regulating mechanism for its production in muscle. Therefore, glutamine consumption or production in portal-drained viscera (PDV), liver, and hindquarter was measured by determining fluxes and intracellular concentrations after 80% enterectomy or SHAM operation in rats. Moreover, fluxes and intracellular concentrations of several other amino acids, ammonia, and liver urea production were determined concomitantly. After enterectomy, arterial glutamine concentration was increased, PDV glutamine consumption was decreased by 77%, and liver glutamine consumption was unchanged compared with values in SHAM-operated rats. Although hindquarter glutamine production remained unchanged after enterectomy, intracellular glutamate concentration (glutamine precursor) was lower, suggesting that enterectomy induces changes in muscle metabolism without changing the flux of glutamine. For the remaining gut, it was calculated that after enterectomy glutamine consumption per gram remaining gut tissue increased. These results cast doubt on the hypothesis that diminished splanchnic glutamine uptake can reduce muscle glutamine production.

Alanine↗
PubMed2005

Identification of the promoter elements involved in the stimulation of ASCT2 expression by glutamine availability in HepG2 cells and the probable involvement of FXR/RXR dimers.

Expression of the glutamine transport protein ASCT2 in the human hepatoma cell line HepG2 is increased when cells are cultured in the presence of glutamine and this has been shown to be due to stimulation of the ASCT2 promoter. Analysis of a number of promoter constructs localised the activation site to be between bases -653 and -543. Gel shift assays identified an IR-1 repeat within a 24bp region of this sequence which bound at least two nuclear proteins. Protein binding to this site was significantly higher in cells grown in glutamine-containing medium than when glutamine was absent. The identity of the higher molecular weight species binding to this promoter element was likely to be FXR/RXR dimers. Simultaneous overexpression of FXR and RXR increased the promoter activity in cells grown without glutamine to the same extent as did glutamine addition; the effects of glutamine and FXR/RXR expression were not additive. Mutagenesis of the FXR/RXR binding site in the promoter construct abolished glutamine and FXR/RXR stimulation. Real-time PCR showed levels of FXR mRNA were significantly increased in response to glutamine. The activity of the FXR promoter was also increased in response to glutamine. These results show that the stimulation of ASCT2 expression in response to glutamine in part involves binding of FXR/RXR to the ASCT2 promoter.

Amino Acid Transport System ASC↗
PubMed2004

Indole-3-acetic acid increases glutamine utilization by high peroxidase activity-presenting leukocytes.

Indole-3-acetic acid (IAA) is toxic for human tumor cells and in association with horseradish peroxidase (HRP) can be used as a new prodrug/enzyme combination for targeted cancer therapy. The toxic effect of IAA on neutrophils, macrophages and lymphocytes is associated with cell peroxidase activity, which is high in neutrophils and low in lymphocytes. The effect of IAA on glucose and glutamine metabolism in leukocytes presenting different peroxidase activities: neutrophils, thioglycollate-elicited macrophages and lymphocytes was investigated. A time-course effect (from 6 to 48 h in culture) of IAA on glucose and glutamine metabolism of neutrophils, thioglycollate-elicited macrophages, and lymphocytes was then carried out. Addition of IAA (0.25 mM) did not have a marked effect on glucose utilization and lactate formation by the three cell types but it raised glutamine consumption and glutamate production by neutrophils and macrophages. IAA had no effect on glutamine consumption and glutamate production by lymphocytes. A strong relationship was found between glutamine utilization (0.999) and glutamate production (0.999) and peroxidase activity. IAA did not change the activities of hexokinase, glucose-6-phosphate dehydrogenase, citrate synthase, lactate dehydrogenase, and phosphate-dependent glutaminase of 24 h cultured neutrophils and lymphocytes. The effect of IAA (1 mM) on glucose and glutamine metabolism was also investigated by 1 h incubated leukocytes in PBS. IAA did not affect glucose and glutamine metabolism of lymphocytes but enhanced glucose and glutamine metabolism by 1 h incubated neutrophils and thioglycollate-elicited macrophages. IAA caused a marked increase on oxygen consumption by neutrophils, which was more pronounced in the presence of the glutamine as compared to glucose. The stimulation of oxygen consumption leads to a reduction in NADH/NAD+ ratio that activates the flux of substrates through the Krebs cycle. Since glutamine is mainly metabolized through the left hand side of the Krebs cycle, a reduction in the redox state of the cells may accelerate the flux of substrates through glutaminolysis. The toxic results presented here show that the affect of IAA in association with peroxidase involves activation of glutamine metabolism.

Analysis of Variance↗
PubMed2006

Glutamine in the mechanism of ammonia-induced astrocyte swelling.

Brain edema and the subsequent increase in intracranial pressure are the major neurological complications in fulminant hepatic failure (FHF). Brain edema in FHF is predominantly "cytotoxic" due principally to astrocyte swelling. It is generally believed that ammonia plays a key role in this process, although the mechanism by which ammonia brings about such swelling is yet to be defined. It has been postulated that glutamine accumulation in astrocytes subsequent to ammonia detoxification results in increased osmotic forces leading to cell swelling. While the hypothesis is plausible and has gained support, it has never been critically tested. In this study, we examined whether a correlation exists between cellular glutamine levels and the degree of cell swelling in cultured astrocytes exposed to ammonia. Cultured astrocytes derived from rat brain cortices were exposed to ammonia (5 mM) for different time periods and cell swelling was measured. Cultures treated with ammonia for 1-3 days showed a progressive increase in astrocyte cell volume (59-127%). Parallel treatment of astrocyte cultures with ammonia showed a significant increase in cellular glutamine content (60-80%) only at 1-4 h, a time when swelling was absent, while glutamine levels were normal at 1-3 days, a time when peak cell swelling was observed. Thus no direct correlation between cell swelling and glutamine levels was detected. Additionally, acute increase in intracellular levels of glutamine by treatment with the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine (DON) after ammonia exposure also did not result in swelling. On the contrary, DON treatment significantly blocked (66%) ammonia-induced astrocyte swelling at a later time point (24 h), suggesting that some process resulting from glutamine metabolism is responsible for astrocyte swelling. Additionally, ammonia-induced free radical production and induction of the mitochondrial permeability transition (MPT) were significantly blocked by treatment with DON, suggesting a key role of glutamine in the ammonia-induced free radical generation and the MPT. In summary, our findings indicate a lack of direct correlation between the extent of cell swelling and cellular levels of glutamine. While glutamine may not be acting as an osmolyte, we propose that glutamine-mediated oxidative stress and/or the MPT may be responsible for the astrocyte swelling by ammonia.

Ammonia↗
PubMed2003

Glutamate-dependent glutamine, aspartate and serine release from rat cortical glial cell cultures.

Glia play a pivotal role in glutaminergic excitatory neurotransmission in the central nervous system by regulating synaptic levels of glutamate and by providing glutamine as the sole precursor for the neurotransmitter pool glutamate to neurons through the glutamate-glutamine cycle. In the present investigation, we examined the influence of glutamate application on glutamine, serine and aspartate release from rat cortical glial cultures. The glial glutamate transporters rapidly cleared exogenously applied glutamate and this was accompanied by rapid increases in aspartate and glutamine, and a delayed increase in serine levels in the glial-conditioned medium. While glutamate-induced increases in glutamine and serine were sustained for up to 24 h, increases in aspartate lasted only for up to 6 h. The glutamate-induced increases in aspartate and glutamine were dependent both on the concentration and the duration of glutamate stimulus, but were largely insensitive to the inhibition of non-N-methyl-D-aspartate receptors or the metabotropic glutamate receptor 5. Inhibition of the glutamate transporter function by L-trans-pyrrolidine 2,4-dicarboxylate decreased the rate of glutamate uptake but not completely abrogated the uptake process, and this resulted in the attenuation of rate of glutamate induced glutamine synthesis. Dexamethasone treatment increased serine and glutamine levels in conditioned medium and increased glutamate induced glutamine release suggesting an upregulation of glutamine synthase activity. These results further substantiate coupling between glutamate and glutamine, and shed light on glutamate-dependent release of serine and aspartate, which may further contribute to excitatory neurotransmission.

Analysis of Variance↗
PubMed2001

Insulin-like growth factor-I stimulates amino acid transport in a glutamine-deprived human neuroblastoma cell line.

It is still unknown how insulin-like growth factor-I (IGF-I) regulates cancer cell growth in the condition of the limited availability of key nutrients, such as glutamine. We investigated the effects of IGF-I on cell growth and amino acid transport in a glutamine-deprived human neuroblastoma cell line, SK-N-SH. Cell growth was measured, and 3H-labeled amino acid transport was assayed after treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 microM glutamine concentrations. Cell growth rates were dependent on glutamine concentrations. IGF-I stimulated cell growth in both 2 mM and 100 microM glutamine. IGF-I stimulated glutamine transport in 100 microM glutamine with the mechanism of increasing carrier Vmax, but had no effect in 2 mM glutamine. IGF-I also stimulated leucine, glutamate and 2-(methylamino)isobutyric acid transport in 100 microM glutamine. There were significant increases in [3H]thymidine and [3H]leucine incorporation in IGF-I-treated cells in both 2 mM and 100 microM glutamine. These data suggest that IGF-I stimulates cell growth by increasing amino acid transport in the condition of low glutamine levels in a human neuroblastoma cell line. This mechanism may allow to maintain cell growth even in nutrient-deprived tumor tissues.

Amino Acids↗
PubMedDate not supplied

Glutamine requirement of proliferating T lymphocytes.

Glutamine is required for lymphocyte proliferation but the site of glutamine action is not yet known. In this study, the effect of glutamine on key events that occur during lymphocyte activation [interleukin-2 (IL-2) production, IL-2 use, IL-2 receptor expression, transferrin receptor expression] was investigated. Rat or mouse spleen lymphocytes were cultured in the presence of the T-cell mitogen concanavalin A (Con A) and various concentrations of glutamine. There was a trend (not significant) for the ratio of CD4+:CD8+ spleen lymphocytes to increase (from 1.9 to 2.6) as the concentration of glutamine in culture medium increased from 0 to 2 mmol/L. As the concentration of glutamine increased, there was an increase in the proportion of cells expressing the IL-2 receptor (from 30 to 45%) and the transferrin receptor (from 34% to 55%). As the concentration of glutamine increased there was a 2.7-fold increase in the concentration of IL-2 in the culture medium. The IL-2 concentration was decreased when an IL-2 receptor-blocking antibody was included in the culture medium; the IL-2 concentrations measured were taken to indicate the initial Con A-stimulated production of IL-2. In these conditions, the IL-2 concentration in the medium increased 39-fold as the glutamine concentration increased. The use of IL-2 by an IL-2-dependent cell line was dependent on the glutamine concentration in the culture medium. Thus, all four components of lymphocyte activation investigated (IL-2 production, IL-2 use, IL-2 receptor expression, transferrin receptor expression) were dependent on the concentration of glutamine present in the culture medium. Thus, glutamine might provide an early signal in the lymphocyte activation process.

Animals↗
PubMedDate not supplied

Glutamine: an essential amino acid for the gut.

Glutamine is a non-essential amino acid which is produced in sufficient amount by the healthy human body. From experimental work it is known that glutamine is an important nutrient for rapidly dividing cells such as cells from the immune system and the gut. During several conditions a lack of glutamine may occur. This will result in functional disturbances of the immune system and/or the gut. Glutamine is produced mainly by the muscle tissue. A decrease in muscle mass during nutritional depletion may result in decreased glutamine production capacity. Furthermore during critical illness, there is an increased demand for glutamine probably as a result of an increased utilization by the immune system. In addition, patients receiving standard parenteral nutrition do not receive glutamine, until recently, commercial parenteral nutrition did not contain glutamine because of instability of this amino acid during prolonged storage. One of the important functions of the gut is to prevent migration of bacteria and/or toxins from the gut lumen into the systemic circulation. A lack of glutamine may result in deterioration of this intestinal barrier. Supplementation of glutamine to certain patients could be essential. The relation between glutamine and the gut in several situations (nutritional depletion, critical illness, parenteral nutrition) is discussed in this paper.

Amino Acids, Essential↗