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PubMed2005

Combined effects of bovine colostrum and glutamine in diclofenac-induced bacterial translocation in rat.

BACKGROUND AND AIMS: The aim of this study was to examine whether the combined administration of bovine colostrum and glutamine was able to prevent the non-steroidal anti-inflammatory drug (NSAID)-induced gut damage and bacterial translocation (BT) in the rats. METHODS: The animal model population of the study consisted of six groups; control group, diclofenac group, diclofenac with milk group, diclofenac with colostrum group, diclofenac with glutamine group and diclofenac with colostrum and glutamine group. The animals with milk, colostrum or glutamine were fed with low fat milk, liquid colostrum or glutamine by orogastric gavage for 5 days before the diclofenac administration. Intestinal permeability, serum biochemical profiles and intestinal adhesion for assessment of the gut damage, and enteric bacterial overgrowth and BT at the mesenteric lymph nodes, liver, spleen and systemic blood were measured. RESULTS: Diclofenac caused the increase in gut damage, enteric bacterial numbers and BT. Supplements with colostrum or glutamine reduced these changes induced by diclofenac, but this result was not seen for supplementation with low fat milk. Combined administration of colostrum and glutamine reduced diclofenac-induced gut damage and BT as compared to the use of bovine colostrum alone or glutamine alone. CONCLUSIONS: This study suggested that the combined administration of bovine colostrum and glutamine might effectively reduce NSAID-induced gut damage and BT in the rat.

Animals↗
PubMed2004

Insulin-like growth factor-2 activation of intestinal glutamine transport is mediated by mitogen-activated protein kinases.

Insulin-like growth factor-2 (IGF-2) plays a pivotal role in regulating intestinal epithelial metabolism, growth, and proliferation, but its regulatory effects on mucosal cell amino acid transport have not been well studied. The purpose of this in vitro study was to investigate the regulatory mechanisms and intracellular signaling pathways involved in the regulation of IGF-2 on glutamine transport in cultured intestinal cells. Continuous incubation with IGF-2 stimulated glutamine transport activity in cultured IEC-6 cells in a dose- and time-dependent fashion. Prolonged incubation (up to 48 hours) resulted in a 50% increase in transport activity (0.81+/-0.21 nmole/mg protein/min in IGF-2 cells vs. 0.57+/-0.15 nmole/mg protein/min in control cells) and a threefold increase in glutamine transporter ATB(0) mRNA levels. IGF-2 stimulated transport activity by increasing transport maximal capacity (V(max) 4.31+/-0.36 nmole/mg protein/min in IGF-2 cells vs. 2.51+/-0.23 nmole/mg protein/min in control cells) without affecting the transport affinity (K(m) 0.31+/-0.03 mmol/L glutamine in IGF-2 cells vs. 0.28+/-0.03 mmol/L glutamine in control cells). This IGF-2-induced glutamine transport activity was attenuated by actinomycin-D or cycloheximide. The levels of mitogen-activated protein kinases p42/44, MEK1/2, and p38 as well as protein kinase C levels were elevated in IGF-2-treated cells and inhibitors of mitogen-activated protein kinase MEK1 (PD 98059), mitogen-activated protein kinase p38, and protein kinase C (chelerythrine chloride) individually attenuated the IGF-2-induced glutamine transport. These data suggest that IGF-2 stimulates intestinal glutamine uptake in cultured rat intestinal epithelial cells via a mechanism that involves transcription and translation of the transporter. Activation of mitogen-activated protein kinases and protein kinase C cascades are involved in the regulation. This increase in glutamine uptake may occur to support intestinal cell growth and proliferation.

Animals↗
PubMed2005

Glutamine supplement with parenteral nutrition decreases whole body proteolysis in low birth weight infants.

OBJECTIVES: To examine the effect of supplemental glutamine (0.6 g.kg -1 .d -1 ) on whole body protein/nitrogen and glutamine kinetics in low birth weight (LBW) infants receiving parenteral nutrition in the immediate neonatal period. STUDY DESIGN: Premature infants < or =32 weeks gestation with a birth weight from 694 to 1590 g were randomly assigned to either a glutamine-supplemented group (n = 10) or to a control group (n = 10). Tracer isotope studies were performed when the infants were 6 to 7 days old and had been receiving an amino acid intake of approximately 3.0 g.kg -1 .d -1 for at least 3 days. Whole body glutamine and nitrogen kinetics were measured with [5-15N]glutamine, [2H5]phenylalanine, [1-13C, 15 N]leucine, [15N2]urea, and GC-mass spectrometry. RESULTS: Supplemental glutamine was associated with a lower rate of appearance of glutamine ( P = .003), phenylalanine ( P = .001), and leucine C ( P = .003). There was no significant difference in leucine N turnover, urea turnover and plasma cortisol, and C-reactive protein levels in the 2 groups. CONCLUSION: Parenteral glutamine supplement in LBW infants was associated with lower whole-body protein breakdown. Because the decrease in whole body proteolysis is associated with protein accretion, parenteral glutamine supplement may be beneficial in selected populations of LBW infants.

Amino Acids↗
PubMed2005

Glutamine stimulates amino acid transport during ischemia-reperfusion in human intestinal epithelial cells.

BACKGROUND: The potential mechanism of intestinal ischemia-reperfusion (I/R) injury includes oxygen-derived toxic free radicals. We tested the hypothesis that glutamine increases intracellular glutathione, a protective substrate against oxidative stress, by stimulating membrane amino acid transport during I/R using human intestinal epithelial cell line Caco-2. METHODS: Ischemic conditions were obtained by combining both hypoxic (1%O2-5%CO2-94% N2) and nutrient-deprived (Phosphate-Buffered Saline; PBS) conditions. After 2 h of ischemia, re-oxygenation (5%CO2-95% air) was initiated and the culture medium was changed to PBS, PBS supplemented with amino acids (A.A.), and PBS supplemented with 2 mm glutamine plus amino acids (Gln) (reperfusion). After 4 h of reperfusion, the transport of 3H-glutamine, 3H-glutamate, and 3H-leucine was assayed and intracellular glutathione was measured. 3H-thymidine incorporation was measured for the determination of DNA synthesis. Data (mean +/- SD) were analyzed by ANOVA. RESULTS: Ischemia decreased Na+-dependent glutamine, Na+-dependent glutamate, and Na+-independent leucine transport compared with control (P < 0.01). After reperfusion, glutamine and glutamate transport in the PBS and A.A. groups decreased significantly compared with control (P < 0.01), whereas glutamine supplementation increased glutamine transport to the levels in control (P < 0.01) and partially increased glutamate transport (P < 0.01). Leucine transport significantly increased in the A.A. and Gln groups compared with the PBS group. Glutamine significantly increased intracellular glutathione and DNA synthesis compared with the PBS and A.A. groups (P < 0.01). CONCLUSIONS: This study demonstrated that glutamine up-regulates amino acid transport during I/R in human intestinal epithelial cells, possibly resulting in increased intracellular glutathione and DNA synthesis.

Amino Acids↗
PubMed2006

Effects of acute exhaustive physical exercise upon glutamine metabolism of lymphocytes from trained rats.

Transitory immunosupression is reported after intense exercise, especially after an increase in training overload and in overtraining. The influence of intense exercise on plasma hormones and glutamine concentration may contribute to this effect. However, the effect of such exercise-induced changes upon lymphocyte and glutamine metabolism is not known. We compared glutamine metabolism in lymphocytes in sedentary (SED) and trained rats. Rats from the moderate group (MOD) swam for 6 weeks, 1 h/day, in water at 32+/-1 degrees C, with a load of 5.5% body weight attached to the tail. Animals from the exhaustive group (EXT) trained like MOD, with training increasing to 3 times 1 h a day during the last week, with 150 min rest between each bout. Animals were killed immediately after the last training bout. We observed reduced concentrations of plasma glucose (p<0.05), glutamine (p<0.05), glutamate (p<0.05) in EXT compared to SED. In MOD, decreases in glutamine (p<0.05) were observed. Analyzing lymphocyte metabolism, we observed an increase in lactate production and glutamine consumption (p<0.05) in MOD (p<0.05) compared to SED and a decrease in glutamine consumption (p<0.05) and aspartate production in EXT. An increase in the proliferative response of lymphocytes in MOD and EXT was also observed when stimulated by ConA and LPS similarly to SED. Acute exercise promoted decreased glutamine plasma concentration and changes in glutamine metabolism that did not impair lymphocyte proliferation in exhaustive trained rats.

Ammonia↗
PubMed2006

Successful 40-hour preservation of the canine small intestine with the cavitary 2-layer method with glutamine supplementation.

BACKGROUND: We recently reported that the cavitary 2-layer method (cTLM) allowed stable 24-hour preservation of canine intestine. The aim of this study was to examine the possibility of the 40-hour preservation by cTLM that is supplemented with glutamine. METHODS: Canine jejunal segments (40 cm) were allotransplanted heterotopically without storage (group 1), after 40-hour cold storage with University of Wisconsin solution (group 2), cTLM (group 3), UW with 2% glutamine (group 4), or cTLM with 2% glutamine (group 5). Mucosal glutamine, histidine, tryptophan, glutathione, and adenosine triphosphate concentrations were determined immediately after preservation. At day 7 after the transplantation, maltose absorption test and histopathologic analysis were performed. RESULTS: Mucosal glutamine concentrations increased significantly with glutamine supplementation during preservation in groups 4 and 5 (P < .01). Mucosal adenosine triphosphate levels in cTLM groups (groups 3 and 5) were similar to those in group 1; group 4 showed very low levels after preservation, despite glutamine supplementation. Mucosal glutathione did not differ among groups 2, 3, 4, and 5 and were significantly lower than in group 1. In the absorption test, serum glucose curves showed a peak level by 30 minutes in groups 1 and 5; delayed peaks were seen in groups 2, 3, and 4 compared with group 1. The villous heights were 879, 555, 685, 688, and 773 microm in groups 1, 2, 3, 4, and 5, respectively (group 1 vs group 2, 3, and 4: P < .05). CONCLUSION: cTLM that was supplemented with glutamine extended a safe preservation period up to 40 hours in canine segmental small intestinal transplantation, although this study failed to elucidate a precise mechanism of the glutamine beneficial effect on the graft mucosa.

Adenosine Diphosphate↗
PubMed2000

Characteristics of L-glutamine transport during Caco-2 cell differentiation.

Glutamine is the main fuel of intestinal epithelial cells, as well as a precursor for the intense nucleotide biosynthesis which arises with the rapid turnover of enterocytes. In order to determine whether glutamine uptake may vary as a function of metabolic demand, glutamine transport across the brush-border membrane of differentiating Caco-2 cells has been investigated. The uptake of L-[(3)H]glutamine was measured between day 7 and day 21 post-seeding. Kinetic analysis with glutamine concentrations ranging from 6.25 microM to 12.8 mM revealed the involvement of high affinity Na(+)-dependent (K(t)=110 microM) and low affinity Na(+)-independent (K(t)=900 microM) transport components at day 7. Both components were partially inhibited by L-lysine in a competitive fashion, suggesting that four different systems were responsible for glutamine uptake: B(0), B(0,+), b(0,+) and L. All four systems were present during the differentiation process, with systems L and B(0) being responsible for up to 80% of glutamine uptake. Caco-2 cell differentiation was associated with a marked decrease in L-glutamine uptake, which affected both the Na(+)-dependent and the Na(+)-independent components. In contrast to glucose uptake, the development of L-glutamine uptake across the brush-border membrane of Caco-2 cells may reflect an adjustment to cell metabolic demand rather than the progressive appearance of a vectorial transport process.

Binding, Competitive↗
PubMed1997

Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery.

Taurine and glutamine are the most abundant intracellular free amino acids in mammalian hearts where changes in their intracellular concentrations are likely to influence a number of cellular activities. In this study we investigated the effects of ischaemia and reperfusion on the intracellular concentrations of taurine and glutamine in the hearts of patients undergoing coronary artery bypass surgery using cold crystalloid or cold blood cardioplegic solutions. Ischaemic arrest (30 min), using cold crystalloid cardioplegic solution (n = 19), decreased the intracellular concentrations (micromol/g wet weight) of taurine (from 9.8 +/- 0.8 to 7.7 +/- 0.7, P < 0.05) and glutamine (8.7 +/- 0.5 to 7.2 +/- 0.6). After 20 min of normothermic reperfusion the fall in taurine and glutamine was maintained (7.5 +/- 0.5 and 7.4 +/- 0.7 for taurine and glutamine respectively). Myocardial ischaemic arrest with cold blood cardioplegic solution (n = 16) did not cause a significant fall in tissue taurine or glutamine. However, on reperfusion there was a marked fall in the intracellular concentrations of taurine (9.4 +/- 0.5 to 6.5 +/- 0.7) and glutamine (8.0 +/- 0.7 to 5.8 +/- 0.4). The fall in amino acids was associated with a fall in ATP and a rise in tissue lactate. This work demonstrates that irrespective of the cardioplegic solution used to arrest the heart, there is a marked fall in tissue taurine and glutamine which may influence the extent of recovery following surgery. The fall in taurine is largely due to efflux whereas changes in glutamine are due to both transport and metabolism. Ischaemia, hypothermia and changes in the transmembrane concentration gradients are the likely factors responsible for the changes in tissue amino acids.

Adenosine Triphosphate↗
PubMed2001

Glutamine is the major precursor for GABA synthesis in rat neocortex in vivo following acute GABA-transaminase inhibition.

The objective of the present study was to assess the degree to which astrocytic glutamine provides carbon for net synthesis of GABA in the rat neocortex in vivo. Isotopic labeling of GABA and glutamate from astrocytic glutamine was followed in halothane anesthetized and ventilated rats during an intravenous infusion of [2-(13)C]glucose. A net increase in GABA was achieved by administration of the GABA-transaminase inhibitor, gabaculine to suppress catabolism of GABA and recycling of (13)C label. (13)C Percentage enrichments of GABA, glutamate and glutamine were assessed in tissue extracts using (13)C-edited (1)H nuclear magnetic resonance at 8.4 T. GABA levels increased 2.6 micromol/g at 2 h and 6.1 micromol/g at 5 h after gabaculine, whereas glutamate and glutamine decreased in toto by 5.6 micromol/g at 2 h and 3.1 micromol/g at 5 h. Selective enrichment of glutamine, glutamate, and GABA C3's over other carbon positions was observed consistent with a precursor role for astrocytic glutamine. Between 1 h (control) and 3 h (gabaculine-treated) of [2-(13)C]glucose infusion, (13)C percentage enrichment increased in glutamine C3 (from 3.2+/-0.5 to 7.0+/-0.9%), glutamate C3 (from 1.8+/-0.5 to 3.4+/-0.9%), and GABA C3 (from 2.7+/-1.6 to 4.8+/-0.4%). The measured incremental [3-(13)C]GABA concentration (0.15 micromol/g) was close to the predicted value (0.13 micromol/g) that would be expected if the increase in GABA were produced entirely from glutamine compared to glutamate (0.07 micromol/g) based on the average precursor enrichments between 1 and 3 h. We conclude that glutamine is the major source of GABA carbon in the rat neocortex produced acutely following GABA-T inhibition by gabaculine in vivo.

4-Aminobutyrate Transaminase↗
PubMed1997

Glutamine transport in cerebellar granule cells in culture.

In the present study, uptake of glutamine by rat cerebellar granule cells, a predominantly glutamatergic nerve cell population, has been investigated. Glutamine is taken up by granule cells via at least three transport systems, A, ASC and L. The L-type low affinity system (K(m) = 2.6 mM) is the major transport system in the absence of Na+. The systems A and ASC represent the Na(+)-dependent transport routes, both with almost identical high affinity for glutamine (K(m) = 0.26 mM). Similar transport systems for glutamine are also found in cerebral cortical neurons, a predominantly GABAergic nerve cell population, and cerebral cortical astrocytes. The glutamine transport properties in granule cells, however, show a series of differences from that of cortical neurons and astrocytes: (1) uptake of glutamine by granule cells is primarily mediated by system A (54%), while contributions by system A in cortical neurons and astrocytes are less than 30%; (2) granule cells exhibit strikingly higher transport efficiency for glutamine (V(max)/K(m) = 20 min(-1) for system A as compared to the V(max)/K(m) ratio of 5 min(-1) in cortical neurons and astrocytes), and (3) the initial uptake rates and the steady-state accumulation levels of glutamine are two- to threefold higher in granule cells than that of cortical neurons and astrocytes. These results taken together suggest that in accordance with the important need to replenish the neurotransmitter pool of glutamate, glutamatergic neurons exhibit highly efficient transport systems to accumulate glutamine, one of the major precursors of glutamate.

Animals↗
PubMed1998

Enteral glutamine does not enhance the effects of hepatocyte growth factor in short bowel syndrome.

PURPOSE: This study was designed to determine if luminally administered glutamine alone functions as a growth factor or is synergistic with hepatocyte growth factor (HGF) after massive small bowel resection (MSBR). METHODS: Twenty Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later the rats were divided into four groups: group 1, control, no further treatment (n = 5); group 2 received glutamine (4% of total food intake per day) via an orogastric tube (n = 5); group 3 received intraluminal HGF via a jejunostomy tube at 75 microg/kg/d (n = 5); and group 4 received glutamine and HGF at the same doses, respectively. After a 14-day HGF infusion, glutamine feeding, or both combined, [C14] glycine absorption (micromol/L/cm2 intestine) and mucosal DNA and protein content (microg/mg mucosa) were measured in the remaining small bowel. RESULTS: Glutamine alone had no effect on substrate absorption and protein or DNA content. HGF increased galactose absorption (106% increase over control, P<.01), glycine absorption (95% increase over control, P<.05), protein content (44% increase over control, P<.01), and DNA content (32% increase over control, P<.01). The combination of glutamine and HGF did not prove to be synergistic. CONCLUSIONS: These data demonstrate that in this short bowel model, glutamine alone did not enhance intestinal function. Furthermore, glutamine is not synergistic with HGF. This study suggests that glutamine alone may not be useful clinically in patients with inadequate intestinal function.

Adaptation, Physiological↗
PubMed1995

Glutamine-mediated regulation of heat shock protein expression in intestinal cells.

BACKGROUND: Glutamine is crucial in the growth and protection of intestinal mucosa; the molecular mechanisms for these effects are not known. Heat shock proteins (hsp) are stress-responsive genes that protect cells from various injuries. The purpose of this study was to determine whether glutamine alters hsp expression in intestinal cells after injury. METHODS: IEC-6 (rat intestinal crypt) cells were grown to 80% confluence, rinsed free of medium and serum, and then grown in medium containing various concentrations of L-glutamine (0.5 to 8.0 mmol/L) for 24 hours. Cells were then exposed to heat shock (43 degrees C for 1 hour) and RNA and protein were extracted at 0, 2, 8, and 24 hours after heat shock. Northern hybridizations were performed using an hsp 70 complementary DNA. Western blots were performed by using antibodies specific to the inducible and constitutive forms of hsp70. RESULTS: Northern blot analysis demonstrated a fourfold stimulation of hsp70 messenger RNA 2 hours after heat shock in IEC-6 cells supplemented with 8.0 mmol/L glutamine compared with 0.5 and 1.0 mmol/L glutamine. In addition, inducible Hsp70 protein levels were increased threefold in IEC-6 cells given glutamine (8.0 mmol/L) at 24 hours after heat shock. CONCLUSIONS: Glutamine augments hsp70 messenger RNA and protein expression in gut-derived IEC-6 cells after injury. Our findings demonstrate a novel mechanism for the enhanced cytoprotection of gut mucosa conferred by administration of glutamine and suggest that supplemental glutamine may be required after injury to enhance expression of stress-responsive genes in the gut.

Animals↗
PubMed1999

Glutamine effects on permeability and ATP content of jejunal mucosa in starved rats.

INTRODUCTION: Starvation induces an increase in intestinal permeability that can be of importance to intestinal integrity. Glutamine is the principal energy source for intestinal enterocytes and is considered essential for gut metabolism, structure and function. The aim of this study was to investigate whether glutamine could improve the ATP content of the mucosa of starved rats and attenuate the permeability perturbation during incubation in vitro in Ussing chamber. METHODS: Segments of jejunum from rats starved for 48 h were mounted in Ussing chambers. Glutamine was added to Krebs-buffer at 0.6mM, 3mM, 6mM and 30mM concentrations on the mucosal side. Cr-EDTA permeation, ATP content of the epithelium mucosa and electrophysiology were studied during 180 min of incubation in Ussing chambers. RESULT: These was a negative linear correlation between ATP content and(51)Cr-EDTA permeability in stripped mucosa. ATP content was reduced in all groups during the experiment. When 30 mM glutamine was added on the mucosal side there was an increase in(51)Cr-EDTA permeability (P< 0.001). There was no effect of glutamine on transepithelial resistance but higher concentrations of glutamine (>3mM) significantly increased the short circuit current. CONCLUSION: Supplementing glutamine to the mucosal side in the Ussing chamber led to an increase in ion pump activity and to an increase in paracellular permeability at the 30mM glutamine concentration. Glutamine did not restore the intracellular ATP level. The increase in permeability was inversely correlated to the mucosal ATP content.

Adenosine Triphosphate↗
PubMed2003

Prevention of chemotherapy and radiation toxicity with glutamine.

GOALS OF THE WORK: Malignancy produces a state of physiologic stress that is characterized by a relative deficiency of glutamine, a condition that is further exacerbated by the effects of cancer treatment. Glutamine deficiency may impact on normal tissue tolerance to antitumor treatment, and may lead to dose reductions and compromised treatment outcome. Providing supplemental glutamine during cancer treatment has the potential to abrogate treatment-related toxicity. We reviewed the available data on the use of glutamine to decrease the incidence and severity of adverse effects due to chemotherapy and/or radiation in cancer patients. METHODS: We performed a search of the MEDLINE database during the time period 1980-2003, and reviewed the English language literature of both human and animal studies pertaining to the use of glutamine in subjects with cancer. We also manually searched the bibliographies of published articles for relevant references. MAIN RESULTS: The available evidence suggests that glutamine supplementation may decrease the incidence and/or severity of chemotherapy-associated mucositis, irinotecan-associated diarrhea, paclitaxel-induced neuropathy, hepatic veno-occlusive disease in the setting of high dose chemotherapy and stem cell transplantation, and the cardiotoxicity that accompanies anthracycline use. Oral glutamine supplementation may enhance the therapeutic index by protecting normal tissues from, and sensitizing tumor cells to chemotherapy and radiation-related injury. CONCLUSIONS: The role of glutamine in the prevention of chemotherapy and radiation-induced toxicity is evolving. Glutamine supplementation is inexpensive and it may reduce the incidence of gastrointestinal, neurologic, and possibly cardiac complications of cancer therapy. Further studies, particularly placebo-controlled phase III trials, are needed to define its role in chemotherapy-induced toxicity.

Anthracyclines↗
PubMed2002

II. Glutamine and glutamate.

Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine via glutamate is converted to alpha-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue. Our aim here is to review on some amino acids with high functional priority such as glutamine and to define their effective activity in human health and pathologies.

Animals↗
PubMed2002

Relation between glutamine, branched-chain amino acids, and protein metabolism.

The branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) are the major nitrogen source for glutamine and alanine synthesis in muscle. Synthesis of glutamine, alanine, and BCAA use is activated in critical illnesses such as in sepsis, cancer, and trauma. The use of glutamine often exceeds its synthesis, resulting in the lack of glutamine in plasma and tissues. In critical illness, resynthesis of BCAA from branched-chain keto acids is activated, particularly in hepatic tissue. The BCAA released to circulation may be used for protein synthesis or synthesis of alanine and glutamine. Glutamine and/or alanine infusion has an inhibitory effect on the breakdown of body proteins and decreases BCAA catabolism in postabsorptive control, endotoxemic, and irradiated rats. Decreased protein breakdown also was observed when glutamine synthesis was activated by ammonia infusion. In conclusion some favorable effects of BCAA supply can be explained by its role in the synthesis of glutamine and some positive effects of glutamine exogenous supply can be explained by its effect on metabolism of BCAA.

Alanine↗
PubMed2002

Is glutamine beneficial in ischemic heart disease?

OBJECTIVE: Glutamine enhances recovery from acute normothermic ischemia in isolated rat heart by a dose-dependent effect (Khogali et al. J Mol Cell Cardiol 1998;30:819). We compared the cardioprotective effects of equimolar concentrations of glutamine, glutamate, and aspartate in isolated rat heart. We also explored the potential cardioprotective effects of glutamine in patients with chronic stable angina. METHODS: The isolated perfused working rat heart was subjected to ischemia, followed by reperfusion with or without an amino acid (2.5 mM). Patients with chronic stable angina received a single oral dose of glutamine (80 mg/kg) or placebo in a double-blind, random fashion 40 min before a standard Bruce exercise test. RESULTS: Postischemic reperfusion of isolated rat heart with glutamine (but not with glutamate or aspartate) resulted in full recovery of cardiac output. Only glutamine prevented the decrease in the myocardial ratio between adenosine triphosphate to adenosine diphosphate and significantly enhanced the myocardial ratio of reduced to oxidized glutathione. A single oral dose of glutamine given to patients with chronic stable angina significantly increased plasma glutamine concentration from 419 to 649 microM and delayed time to onset of more than 1.0 mm of ST segment depression on the ECG by 38 s. CONCLUSION: Glutamine may be cardioprotective in patients with coronary heart disease.

Adenosine Diphosphate↗
PubMedDate not supplied

The use of glutamine in the treatment of gastrointestinal disorders in man.

The human gastrointestinal tract (GIT) is a major site of glutamine utilisation accounting for more than half of the net splanchnic utilisation (approximately 15 g/day) of glutamine obtained from the systemic circulation. Dietary glutamine (approximately 5 g/day) is less important than circulating glutamine, especially in disease conditions associated with substantial reduction in food intake. Glutamine has multiple effects on the structure and function of the GIT, and effects in improving morbidity and mortality in animal models of GIT damage has led to a series of studies in man, which have produced variable results. Glutamine administration to treat mucositis of the upper GIT (mouth, oesophagus) due to cytotoxic drug therapy, has produced no evidence of benefit. Early studies suggested improved healing, as do recent studies of small intestinal mucositis resulting from chemotherapy. Investigations in colitis are lacking although in experimental rat models of colitis no benefit has been reported. Multiple explanations can be put forward to explain the overall results, including the GIT distribution of enzymes involved in glutamine metabolism. Apart from the lower stomach in man (upper stomach in the rat) there is very little weak activity of glutamine synthetase, suggesting that the gut derives glutamine formed in other tissues and from the diet. The activity of glutaminase, which is key flux generating enzyme involved in glutaminolysis is very weak in mucosa with stratified squamous epithelium (oesophagus), where intermediate in the same intestine, and highest in the small intestinal mucosa which accounts for about 80% of the total glutaminase in the entire human GIT mucosa.

Administration, Oral↗