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PubMed1990

Neuronal glutamine utilization: glutamine/glutamate homeostasis in synaptosomes.

The synaptosomal metabolism of glutamine was studied under in vitro conditions that simulate depolarization in vivo. With [2-15N]glutamine as precursor, the [glutamine]i was diminished in the presence of veratridine or 50 mM KCl, but the total amounts of [15N]glutamate and [15N]aspartate formed were either equal to those of control incubations (veratridine) or higher (50 mM [KCl]). This suggests that depolarization decreases glutamine uptake and independently augments glutaminase activity. Omission of sodium from the medium was associated with low internal levels of glutamine which indicates that influx occurs as a charged Na(+)-amino acid complex. It is postulated that a reduction in membrane potential and a collapse of the Na+ gradient decrease the driving forces for glutamine accumulation and thus inhibit its uptake and enhance its release under depolarizing conditions. Inorganic phosphate stimulated glutaminase activity, particularly in the presence of calcium. At 2 mM or lower [phosphate] in the medium, calcium inhibited glutamine utilization and the production of glutamate, aspartate, and ammonia from glutamine. At a high (10 mM) medium [phosphate], calcium stimulated glutamine catabolism. It is suggested that a veratridine-induced increase in intrasynaptosomal inorganic phosphate is responsible for the enhancement of flux through glutaminase; calcium affects glutaminase indirectly by modulating the level of free intramitochondrial [phosphate]. Because phosphate also lowers the Km of glutaminase for glutamine, augmentation of the amino acid breakdown may occur even when depolarization lowers [glutamine]i. Reducing the intrasynaptosomal glutamate to 26 nmol/mg of protein had little effect on glutamine catabolism, but raising the pH to 7.9 markedly increased formation of glutamate and aspartate. It is concluded that phosphate and H+ are the major physiologic regulators of glutaminase activity.

Animals↗
PubMed1979

Characteristics of glutamine metabolism by rat kidney tubules: a carbon and nitrogen balance.

The metabolism of glutamine by a suspension of rat kidney tubules was studied in vitro. The influence of duration of incubation, glutamine concentration, and metabolic state of the donor animals was investigated. The relative importance of glucose synthesis, amino acid production, and oxidation to CO2 was estimated by drawing a complete balance of the nitrogens and the carbon chains of the extracted glutamine. It was found that the initial (first 15 min) rate of glutamine utilization was significantly greater than the subsequent rate due to an initial, but transient, extracellular accumulation of glutamate. This phenomenon was suppressed when a small amount of glutamate was added to the incubation medium. Glucose production constitutes the major fate for glutamine metabolism. No net oxidation of glutamine could be detected with 1 mM glutamine during the first 30 min. However, glutamine oxidation becomes significant after prolonged incubation (16% at 120 min). The metabolic fate of glutamine differs when 5 or 10 mM are presented to the tubules, glutamate production and oxidation to CO2 becoming more important. Metabolic acidosis or a 48-h fast increases glutamine extraction and enhances its utilization glucose synthesis while they depress glutamate accumulation and oxidation to CO2. Metabolic alkalosis has the opposite effect. It is concluded that the metabolism of glutamine in vitro is dependent on the conditions of the study. Furthermore, total oxidation to CO2 is not a major fate for glutamine metabolism at physiological concentration and is not enhanced by acidosis in the rat kidney in vitro.

Amino Acids↗
PubMed2006

Heat induction of heat shock protein 25 requires cellular glutamine in intestinal epithelial cells.

Glutamine is considered a nonessential amino acid; however, it becomes conditionally essential during critical illness when consumption exceeds production. Glutamine may modulate the heat shock/stress response, an important adaptive cellular response for survival. Glutamine increases heat induction of heat shock protein (Hsp) 25 in both intestinal epithelial cells (IEC-18) and mesenchymal NIH/3T3 cells, an effect that is neither glucose nor serum dependent. Neither arginine, histidine, proline, leucine, asparagine, nor tyrosine acts as physiological substitutes for glutamine for heat induction of Hsp25. The lack of effect of these amino acids was not caused by deficient transport, although some amino acids, including glutamate (a major direct metabolite of glutamine), were transported poorly by IEC-18 cells. Glutamate uptake could be augmented in a concentration- and time-dependent manner by increasing either media concentration and/or duration of exposure. Under these conditions, glutamate promoted heat induction of Hsp25, albeit not as efficiently as glutamine. Further evidence for the role of glutamine conversion to glutamate was obtained with the glutaminase inhibitor 6-diazo-5-oxo-l-norleucine (DON), which inhibited the effect of glutamine on heat-induced Hsp25. DON inhibited phosphate-dependent glutaminase by 75% after 3 h, decreasing cell glutamate. Increased glutamine/glutamate conversion to glutathione was not involved, since the glutathione synthesis inhibitor, buthionine sulfoximine, did not block glutamine's effect on heat induction of Hsp25. A large drop in ATP levels did not appear to account for the diminished Hsp25 induction during glutamine deficiency. In summary, glutamine is an important amino acid, and its requirement for heat-induced Hsp25 supports a role for glutamine supplementation to optimize cellular responses to pathophysiological stress.

Animals↗
PubMed1997

Glutamine utilization by rat neutrophils: presence of phosphate-dependent glutaminase.

The capacity of rat neutrophils to utilize glutamine was investigated by 1) determination of oxygen consumption in the presence of glucose or glutamine, 2) measurement of maximal activity of phosphate-dependent glutaminase, 3) Northern blot, Western blot, and immunocytochemical detection of glutaminase, and 4) measurement of glutamine utilization and also production of ammonia, glutamate, aspartate, alanine, and lactate and decarboxylation of [U-14C]glutamine in cells incubated for 1 h. The rate of respiration by isolated neutrophils in the absence of added substrate was 5.0 nmol x min(-1) x 10(7) cells(-1). Maximal activity of phosphate-dependent glutaminase was 56 nmol x min(-1) x mg protein(-1) in freshly obtained neutrophils; the Michaelis-Menten constant was 3.5 mM for glutamine. This enzyme activity was inhibited by 2 mM glutamate, 2 mM oxoglutarate, and 2 mM NH4Cl. The presence of glutaminase protein (65 kDa) was confirmed by Western blot and immunocytochemical detection and the presence of the mRNA (6.0 kb) by Northern blot analysis. Glutamine was utilized by neutrophils incubated for 1 h at a rate of 12.8 nmol x min(-1) x mg protein(-1) when the amino acid was added to the medium at 2 mM, which is three to four times higher than the physiological concentration. In the presence of 0.5 mM glutamine, the amino acid was utilized at a rate of 2.9 nmol x min(-1) x mg protein(-1). The addition of 0.5 mM glutamate to the incubation medium caused a marked reduction (by 70%) in glutamine utilization by neutrophils. Glucose was utilized at 7.7 nmol x min(-1) x mg protein(-1) when cells were incubated in 5 mM glucose. The conversion of [U-14C]glutamine to 14CO2 was very low: <1% was totally oxidized. The formation of ammonia was approximately 27% of glutamine utilization, and the conversion of glutamine to glutamate, aspartate, alanine, and lactate accounted for approximately 84.6% of the total amino acid utilized by neutrophils. In this study, evidence is presented that, in addition to lymphocytes and macrophages, neutrophils also utilize glutamine.

Animals↗
PubMed1986

Glutamine and glutamate kinetics in humans.

To study glutamate and glutamine kinetics, 4-h unprimed intravenous infusions of L-[15N]glutamate, L-[2-15N]glutamine, and L-[5-15N]-glutamine were administered to healthy young adult male subjects in the postabsorptive state. Arterialized-venous blood samples were drawn and analyzed for glutamate and glutamine 15N enrichments. The fractional turnover rates of the tracer-miscible glutamate and glutamine pools were fast, 8.0 and 2.8% min-1, respectively. The glutamate tracer-miscible pool accounted for less than one-tenth the estimated free glutamate pool in the body. The plasma glutamate amino N, glutamine amino N and glutamine amide N rates of appearance were 83 +/- 22 (means +/- SD), 348 +/- 33, and 283 +/- 31 mumol X kg-1 X h-1, respectively. The glutamine amide N appearance rate was 20% slower than the amino N appearance rate, indicating that glutamine transaminase is an active pathway in human glutamine metabolism. From measurement of transfer of tracer 15N, we found that only 5% of the glutamine synthesized in cells and released into plasma was derived from intracellular glutamate that had mixed with plasma. These data demonstrate that intravenously administered tracers of glutamate or glutamine do not mix thoroughly with the intracellular pools, and their measured kinetics reflect transport rates through plasma rather than whole-body fluxes.

Adult↗
PubMed1997

Glutamine or glutamate release by the liver constitutes a major mechanism for nitrogen salvage.

The aim of the present study was to investigate mechanisms of N salvage by the liver when a diet is protein deficient. For this purpose, rats were adapted to a slightly deficient (11% casein) or moderately surfeit (22% casein) dietary protein level. Animals were sampled during the postprandial or the postabsorptive period, and fluxes across the digestive tract and liver were determined. During the postabsorptive period there was a negative balance of glutamine across the digestive tract in both diet groups. During the postprandial period the digestive balance of glutamine was still negative, despite a substantial supply of dietary glutamine and glutamate, suggesting that glutamine utilization is maximal during this period. There was a net production of glutamate and glutamine by the liver in both diet groups, but glutamine release was 73% higher in rats fed the low-protein diet. In these animals, because of the relatively low capacity of ureagenesis, N utilization was shifted toward glutamine synthesis: overall uptake of amino acids by the liver was approximately 5.3 micromol/min, and net release of glutamine + glutamate was approximately 2.9 micromol/min (hence a 55% cycling, on a molar basis). This cycling was only 12% in rats adapted to the 22% casein diet. When liver ammonia uptake was taken into account, N cycling showed parallel changes: 64% or 15% in rats adapted to the 11% or 22% casein diet, respectively. Besides glutamine delivery, glutamate was also released by the liver, representing an N source for extrasplanchnic tissues. With protein-deficient diets, hepatic glutamine delivery mainly serves to fulfill substrate needs for intestinal metabolism, which represents a mechanism for N salvage. This shift of N metabolism from urea toward glutamine production may imply a glutamate transfer from periportal to glutamine-synthesizing perivenous hepatocytes.

Absorption↗
PubMed2000

Effect of cholera toxin on glutamine metabolism and transport in rabbit ileum.

The aim of the present study was to evaluate the effect of cholera toxin on energy balance from intestinal glutamine metabolism and oxidation, glutamine-dependent sodium absorption, and cholera toxin-dependent ion flux. Cholera toxin-stimulated sodium and L-glutamine ileal transport and metabolism were studied in Ussing chambers. Glutamine (10 mM) transport and metabolism were simultaneously studied using (14)C flux and HPLC. In the same tissues, the flux of each amino acid was studied by HPLC, and glutamine metabolism and oxidation were studied by the determination of amino acid specific activity and (14)CO(2) production. In control tissues, glutamine stimulated sodium absorption and was mainly oxidized. The transepithelial flux of intact glutamine represented 45% of glutamine flux across the luminal membrane. The other metabolites were glutamate and, to a lesser degree, citrulline, ornithine, and proline. Cholera toxin did not alter glutamine-stimulated sodium absorption, glutamine oxidation, transport, and metabolism. In conclusion, the present results indicate that cholera toxin does not alter glutamine intestinal function and metabolism. In addition, approximately 95% of the energy provided by glutamine oxidation remains available to the enterocyte.

Animals↗
PubMed2000

Interaction of glutamine and arginine on cerebrovascular reactivity to hypercapnia.

Glutamine is purported to inhibit recycling of citrulline to arginine and to limit nitric oxide release in vitro. However, vasoactive effects of glutamine have not been clearly demonstrated in vivo. During hyperammonemia, impaired cerebrovascular reactivity to CO(2) is related to glutamine accumulation. We tested the hypotheses that 1) glutamine infusion in the absence of hyperammonemia impairs cerebrovascular CO(2) reactivity and 2) arginine infusion preserves CO(2) reactivity during glutamine infusion and during hyperammonemia. Pentobarbital sodium-anesthetized rats were equipped with a closed cranial window for measuring pial arteriolar diameter. Intravenous infusion of 3 mmol. kg(-1). h(-1) of L-glutamine for 6 h produced threefold increases in plasma and cerebrospinal fluid concentrations. Dilation to hypercapnia was reduced by 45% compared with that of a time control group at 6 h but not at 3 h of glutamine infusion. Coinfusion of 2 mmol. kg(-1). h(-1) of L-arginine with glutamine maintained the hypercapnic vasodilation at the control value. Infusion of ammonium acetate at a rate known to produce threefold increases in cortical tissue glutamine concentration resulted in no significant hypercapnic vasodilation. Coinfusion of arginine with ammonium acetate maintained hypercapnic vasodilation at 60% of the control value. Arginine infusion did not augment hypercapnic vasodilation in a control group. We conclude that glutamine modulates cerebrovascular CO(2) reactivity in vivo. Glutamine probably acts by limiting arginine availability because the vascular inhibitory effect required >3 h to develop and because arginine infusion counteracted the vascular effect of both endogenously and exogenously produced increases in glutamine.

Acetates↗
PubMed1995

Glutamine and glucose metabolism in enterocytes of the neonatal pig.

Glutamine and glucose metabolism was studied in 0- to 21-day-old pig enterocytes. Cells were incubated at 37 degrees C for 30 min in Krebs-Henseleit bicarbonate buffer (pH 7.4) in the presence of 2 mM [U-14C]glutamine with or without 5 mM glucose, or 5 mM [U-14C]glucose with or without 2 mM glutamine. Glutamine was metabolized to ammonia, glutamate, alanine, aspartate, CO2, citrulline, ornithine, and proline, whereas glucose was converted to lactate, pyruvate, and CO2 in pig enterocytes. CO2 production from glutamine accounted for 32-36% and 3-4% of utilized glutamine carbons in 0- to 7-day-old and 14- to 21-day-old pigs, respectively. The rates of O2 consumption and metabolism of glutamine and glucose decreased in enterocytes from 2- to 14-day-old pigs compared with 0-day-old pigs. By day 14 after birth, the oxidation of glutamine and glucose as well as citrulline production had decreased by 90-95%. Arginine synthesis from glutamine occurred in cells from 0- to 7-day-old pigs but not 14- to 21-day-old ones. Glucose (5 mM) had no effect on glutamine utilization and oxidation or the production of glutamate and arginine but stimulated the formation of alanine, citrulline, and proline at the expense of aspartate. In contrast, glutamine (2 mM) inhibited glycolysis and glucose oxidation in cells from 0- to 7-day-old pigs and had no effects in 14- to 21-day-old pigs. As a result, glutamine contributed approximately 2-fold greater amounts of ATP to 0- to 7-day-old pig enterocytes than glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

Tubular CO2 production from glutamine in the rat: segmental profile and modulation.

The present study was designed to test whether tubular carbon dioxide production from the carbon skeleton of uniformly 14C-labelled glutamine exhibits quantitative and qualitative segmental heterogeneity. Our results show that CO2 production from glutamine in the proximal convoluted tubule (PCT) was dependent on substrate concentrations and is saturable at 10(-4) M of glutamine. Glutamine oxidation was demonstrable in all nephron segments examined. The PCT is the quantitatively predominant site of glutamine oxidation. Intermediate nephron segments, however, such as the thick ascending limb (MAL) and the distal convoluted tubule possess a significant capacity for glutamine oxidation, particularly when examined in terms of tubular protein content. Modulation of glutamine oxidation by extracellular pH was segment specific. Stimulation by acidosis and inhibition by alkalosis were observed in the PCT while carbon dioxide production from glutamine in the MAL was pH-insensitive. Glutamine oxidation was closely linked to sodium transport and greatly decreased by inhibition of Na-K-ATPase. In both the PCT and MAL, glutamine oxidation was inhibited by high extracellular potassium concentrations and in the PCT enhanced by extracellular hypokalemia. N-Ethyl maleiamide, an inhibitor of proton ATPase, led to almost complete cessation of CO2 production from the substrate in both PCT and MAL. Acetazolamide, an inhibitor of carbonic anhydrase, led to a partial reduction in carbon dioxide formation in the PCT, but did not affect glutamine oxidation in the MAL. We conclude that segmental qualitative heterogeneity characterizes oxidation of the carbon skeleton of glutamine with proximal segments showing the predictable effects of pH changes and carbonic anhydrase inhibition. The MAL appears to be nonmodulating.

Animals↗
PubMed1972

The effect of glutamine administration on urinary ammonium excretion in normal subjects and patients with renal disease.

The effect of acute changes in the delivery rate of glutamine to the kidney on urinary ammonium excretion was studied in man. Healthy subjects and patients with intrinsic renal disease were studied under three different acid-base conditions: unaltered acid-base balance; NH(4)Cl-induced acidosis; and NaHCO(3)-induced alkalosis. Anhydrous L-glutamine was administered orally in a single dose of 260 mmoles during each of these three acid-base states. We found that endogenous venous plasma glutamine concentration fell during acidosis and rose during alkalosis in both healthy subjects and patients with renal disease. In healthy subjects, orally administered glutamine raised plasma glutamine concentration markedly over a 2-3 hr period. This was accompanied by an increase in urinary ammonium excretion and a rise in urine pH under normal acid-base conditions and during metabolic acidosis. No increase in ammonium excretion occurred when glutamine was administered during metabolic alkalosis in spite of an equivalent rise in plasma glutamine concentration. In patients with renal disease, endogenous venous plasma glutamine concentration was lower than in healthy subjects, perhaps as a result of mild metabolic acidosis. Acute oral glutamine loading failed to increase urinary ammonium excretion significantly during either unaltered acid-base conditions or after NH(4)Cl-induced acidosis, even though plasma glutamine rose as high as in healthy subjects. We conclude from these observations that glutamine delivery to the kidney is a rate-limiting factor for ammonium excretion in healthy subjects, both before and after cellular enzyme adaptation induced by metabolic acidosis. In contrast, in patients with renal disease, glutamine delivery is not rate-limiting for ammonium excretion. Presumably other factors, such as surviving renal mass and the activity of intracellular enzymes necessary for ammonia synthesis limit ammonium excretion in these patients.

Acidosis↗
PubMed1974

Glutamine transport in rat kidney mitochondria in metabolic acidosis.

In order to study factors regulating renal ammoniagenesis, the transport and metabolism of L-glutamine were studied in mitochondria from kidneys of control and acidotic rats. On incubation in 1 mM [(14)C]glutamine, there was production and accumulation of [(14)C]glutamate within the matrix space. However no [(14)C]glutamine was detected in the matrix space, even with 10 mM [(14)C]glutamine as substrate or with inhibition of glutamine deamidation (low temperature, p-chloromercuribenzoate, mersalyl). These results suggest that glutamine crosses the inner membrane by a carrier-mediated step and that this step is rate-limiting in glutamine deamidation. In chronic acidosis there is a fourfold increase in the uptake of radioactivity from [(14)C]glutamine, but not from alpha-ketoglutarate, glutamate, or acetate. In 3-h acidosis, before any increase in extracted glutaminase levels, there is a significant and reproducible increase (39+/-3.8%, n = 25) in matrix uptake of radioactivity from [(14)C]glutamine and also an increased ammonia production (17+/-3.7%, n = 12). Administration of furosemide produces a similar degree of potassium depletion and a greater degree of sodium depletion over 3 h when compared to a 3-h acidosis. However, it produces no change in mitochondrial uptake of radioactivity. These results show that the adaptation of renal glutamine metabolism observed in acidosis is due to the acidosis and is demonstrable in isolated rat kidney mitochondria. The site of adaptation is in the carrier system, which transports glutamine across the inner membrane. The increased transport in acidosis delivers more glutamine to glutaminase, which results in the increased renal ammonia production.

Acetates↗
PubMed1992

Glutamine content of whole proteins: implications for enteral formulas.

In two recent clinical trials in surgical patients, supplementation of total parenteral nutrition with daily doses of 12 or 20 g of glutamine resulted in a diminished loss of free glutamine in skeletal muscle tissue. Studies in animals exploring the use of both enteral and parenteral glutamine supplementation suggest that glutamine may be an essential nutrient in the maintenance of gut structure and function during critical illness. These findings have led to heightened interest in the glutamine content of enteral formulas. This article describes a method for estimating the glutamine content of whole-protein enteral formulas. The average amount of glutamine in selected, whole-protein formulas ranges from a minimum of 3.55 g/4200 kJ to a maximum of 5.15 g/4200 kJ. Although it is still too early to define the safest and most effective dose of glutamine, there are two points regarding glutamine supplementation that clearly merit further investigation: no clinical trials have been conducted to assess the potential benefits of glutamine supplementation of an enteral diet or to assess the effects of using diets containing protein-bound glutamine rather than free glutamine.

Enteral Nutrition↗
PubMedDate not supplied

Safety and metabolic effects of L-glutamine administration in humans.

A series of dose-response studies was conducted to evaluate the clinical safety, pharmacokinetics, and metabolic effects of L-glutamine administered to humans. Initial studies in normal individuals evaluated the short-term response to oral loads of glutamine at doses of 0, 0.1, and 0.3 g/kg. A dose-related increase in blood glutamine occurred after oral loading and elevation of amino acids known to be end products of glutamine metabolism occurred (including alanine, citrulline, and arginine). No evidence of clinical toxicity or generation of toxic metabolites (ammonia and glutamate) was observed. Glutamine was infused intravenously in normal subjects over 4 hr at doses of 0.0125 and 0.025 g/kg/hr. In addition, glutamine was evaluated as a component of parenteral nutrition solutions (0.285 and 0.570 g/kg/day) administered for 5 days to normal subjects. Intravenous administration of glutamine was well tolerated without untoward clinical or biochemical effects. Subsequent studies in patients receiving glutamine-enriched parenteral nutrition for several weeks confirmed the clinical safety of this approach in a catabolic patient population. In addition, nitrogen retention appeared to be enhanced when glutamine was administered at a dose of 0.570 g/kg/day in a balanced nutritional solution providing adequate calories (145% of basal) and protein (1.5 g/kg/day). Nitrogen balance in patients receiving lower doses of glutamine (0.285 g/kg/day) was similar to that in patients receiving standard formulations. Further controlled clinical trials of the metabolic efficacy, tolerance, and dose response of glutamine in other patient groups are necessary to determine the appropriate use of glutamine enrichment of nutrient solutions.

Administration, Oral↗
PubMedDate not supplied

L-glutamine supplementation in home total parenteral nutrition patients: stability, safety, and effects on intestinal absorption.

A study was conducted to determine safety and efficacy of L-glutamine when added to total parenteral nutrition (TPN) solutions of patients receiving TPN in the home. Stability studies were first performed on various concentrations of L-glutamine in TPN solutions mixed by the Pharmix method. These showed that glutamine was stable in home TPN solutions for at least 22 days. The daily home TPN solutions of seven stable patients were then supplemented with glutamine at a dose of 0.285 g/kg of body weight for 4 weeks. The glutamine-TPN solutions were prepared weekly. Five patients received the full 4 weeks of glutamine-TPN. In two patients, administration of glutamine-TPN mixtures was stopped at the end of week 2 and week 3 because of elevations in liver enzymes. A third patient's liver enzymes rose at the end of week 4. These abnormalities subsided after discontinuation of the glutamine-TPN solution. Plasma levels of glutamine increased during the first 3 weeks of supplementation but these increases were not statistically significant. D-Xylose absorption studies performed before and after the administration of glutamine-TPN did not reveal any improvement in small-bowel absorptive capacity. In conclusion, stable glutamine-TPN solutions for use by home TPN patients can be formulated. However, supplementation of home TPN solutions at this dose was associated with apparent hepatic toxicity and did not demonstrate a beneficial effect on intestinal absorptive capacity as measured by D-xylose absorption. Therefore, on the basis of this study, routine supplementation of home TPN solution with glutamine cannot be recommended.

Adult↗
PubMedDate not supplied

Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats.

BACKGROUND: Since tumor-bearing rats are deficient in glutamine, we investigated whether (1) glutamine and glutathione deficiency occur in tumor-bearing rats, (2) glutamine supplementation caused an increase of glutathione levels in host tissues and tumor, (3) glutamine enhances protein synthesis in host tissues, and (4) glutamine stimulated the tumor to synthesize protein and DNA. METHODS: Male Donryu rats were randomized into four groups: (1) non-tumor-bearing rat (NTB) + standard total parenteral nutrition (STPN); (2) NTB + glutamine-supplemented TPN (GTPN); (3) tumor-bearing rat (TB) + STPN; (4) TB + GTPN. On day 0 AH109A rat hepatoma cells were subcutaneously injected into the backs of rats to induce tumor. The animals were maintained on TPN for 6 days from day 10 through day 15. On day 15, 1-14C-leucine was given by a 5-hour continuous infusion (2.0 microCi/h per rat) to determine the fractional synthesis rate and endogenous leucine production. The levels of glutamine and glutathione were measured by HPLC. the tumor DNA synthesis was estimated by bromodeoxyuridine labeling index. RESULTS: Tumor development led to a significant weight loss, but this weight loss was significantly lessened by glutamine supplementation because of an increase in muscle protein synthesis. Glutamine did not enhance tumor weight, protein, and DNA synthesis in the tumor. Tumor development caused a significant reduction of glutathione in the muscle, jejunum, and liver, but supplemented glutamine increased the levels of glutathione in the jejunum. CONCLUSION: Glutamine supplementation is beneficial in preventing deficiencies of glutamine and glutathione and in improving protein metabolism in tumor-bearing rats.

Animals↗
PubMedDate not supplied

Role of glutamine in bacterial transcytosis and epithelial cell injury.

BACKGROUND: L-Glutamine is the principal energy source for small intestinal enterocytes. Diminution of intestinal function, mucosal atrophy, and increased bacterial translocation have been noted during total parenteral nutrition (TPN). In a rat model of glutamine starvation, we previously showed that luminal glutamine is essential for optimal intestinal function. In this study, we examined the effect of apical vs basolateral glutamine on bacterial translocation in a Caco-2 cell culture system and bacteria-induced tissue injury in a weanling rabbit ileal loop model. METHODS: Caco-2 cells were grown in a transwell system. After confluence, apical and basolateral chambers received defined media, and glutamine deprivation was carried out over a 4- to 48-hour period. Escherichia coli transcytosis and structure/function studies were then performed. In a second series of experiments, the effect of intraluminal glutamine supplementation was evaluated in an E. coli-induced tissue injury model in weanling rabbit ileal loops. RESULTS: Expression of disaccharidases, glucoamylase, and Na+/K(+)-adenosine 5'-triphosphatase (ATPase) were significantly reduced when cells were deprived of glutamine from the apical side, and there was increased bacterial translocation across the monolayer. Transepithelial epithelial resistance (TEER) across the monolayer was also reduced in the glutamine-free cultures. Glutamine replenishment over 24 to 48 hours restored the original functions. Basolateral deprivation had a smaller effect on the Caco-2 cells. Typical necrotic mucosal injury caused by E. coli in the ileal loops was blocked by co-infiltration of the loops with glutamine. CONCLUSIONS: This study demonstrates for the first time that the supply of glutamine from the apical side is of critical importance for maintaining optimal structure and function of the enterocytes. The effects are not acute or energy related. These observations have important clinical implications in the management of patients under critical care, including premature infants and patients receiving TPN, for whom lack of glutamine from the luminal side could produce mucosal dysfunction, resulting ultimately in severe atrophic/necrotic complications.

Animals↗
PubMed2007

Enteral glutamine supplementation in critically ill patients with burn injuries: a retrospective case-control evaluation.

STUDY OBJECTIVES: To evaluate the clinical application of enteral glutamine supplementation in critically ill patients and compare the frequency of nosocomial infections in these patients with a historical control group in a burn intensive care unit (BICU), and to assess lengths of stay in the hospital and BICU, mortality rates, and safety profile of glutamine. DESIGN: Retrospective case-control descriptive study. SETTING: A university-affiliated hospital BICU. PATIENTS: Seventeen patients receiving enteral glutamine supplementation and 15 historical control patients who were admitted to the BICU for thermal burn injuries from January 1, 2001-September 30, 2004. MEASUREMENTS AND MAIN RESULTS: Data for patients receiving enteral glutamine supplementation were identified through the pharmacy database, and data for the control patients were identified through the BICU patient registry. No significant differences were noted in baseline characteristics or nutritional parameters and outcomes between the two groups. The mean daily dose and duration of glutamine were 0.52 g/kg and 21.6 days, respectively. The mean number of infections/patient between the glutamine and control groups was similar (2.47 and 2.73, respectively) as was the number of gram-negative infections (1.29 and 1.20, respectively). Bloodstream infections occurred more frequently in the glutamine group (24 vs 8 patients, p=0.0006); however, cellulitis (4 vs 11, p=0.05) and pneumonia (9 vs 15, p=0.15) occurred less often. For the glutamine group versus control group, BICU length of stay (17.9 vs 15.3 days, p=NS), hospital length of stay (32.3 vs 26 days, p=NS), and mortality rates (0% vs 6.7%, p=NS) were similar between groups. No adverse events were attributed to glutamine supplementation. CONCLUSION: Enteral glutamine supplementation was not associated with a change in the cumulative rate of infectious complications compared with the control group, but this was attributed to more cases of bloodstream infections and fewer cases of pneumonia and cellulitis in the glutamine group. Large, prospective, randomized trials designed to detect small but clinically relevant outcomes are needed to definitively determine the effect of enteral glutamine supplementation in the BICU population.

Adolescent↗