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PubMed1998

Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism.

The present study was designed to determine whether sodium phenylbutyrate (phi B) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g.kg-1.day-1) of phi B were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an approximately 25% decline for a dose of 0.36 g phi B.kg-1.day-1. A second group of six healthy adults received 5-h infusions of L-[1-14C]leucine and L-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with phi B (0.36 g.kg-1.day-1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an approximately 26% decline in plasma glutamine concentration from 514 +/- 24 to 380 +/- 15 microM (means +/- SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 +/- 7 vs. 117 +/- 5 mumol.kg-1.h-1; not significant); 3) an approximately 22% rise in leucine oxidation (Ox) from 23 +/- 2 to 28 +/- 2 mumol.kg-1.h-1 (P < 0.01), resulting in an approximately 11% decline in nonoxidative leucine disposal (NOLD = Ra-Ox), an index of protein synthesis, from 100 +/- 6 to 89 +/- 5 mumol.kg-1.h-1 (P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a "glutamine trap" to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decrease estimates of whole body protein synthesis.

Adult↗
PubMed1993

Characterization of Na(+)-independent glutamine transport in rat liver.

In hepatic plasma membrane vesicles (HPMVs) from rat liver, we observed that approximately 40-45% of Na(+)-independent glutamine uptake occurs by a saturable carrier-mediated process. This component of glutamine uptake is mediated by a transport agency distinct from that of previously described systems for the Na(+)-independent transport of amino acids. Transport of glutamine was electroneutral and occurred into an osmotically active space with negligible membrane binding. The model system L substrate 2-amino-2-norbornane-carboxylic acid (BCH) showed no appreciable inhibition of Na(+)-independent glutamine uptake by HPMVs but effectively inhibited the uptake of leucine, a classic system L substrate, in identical vesicle preparations. Further evidence against system L-mediated glutamine transport was provided by the pH dependence and the lack of trans-stimulation of saturable uptake. Competition experiments with selected amino acids revealed a pattern of inhibition of glutamine transport that was inconsistent with assignment of glutamine entry to systems asc, T, or systems for the Na(+)-independent transport of the charged amino acids. This BCH-noninhibitable transport system in HPMVs was highly selective for glutamine, histidine, and, to a lesser extent, asparagine. Inhibition of Na(+)-independent glutamine transport by leucine was noncompetitive in nature. On the basis of Na+ independence, pH sensitivity, absence of trans-stimulation, and an amino acid selectivity similar to that of the previously described hepatic Na(+)-dependent system N, we have provisionally designated the glutamine transport agency described in this article as system "n."

Amino Acids↗
PubMed1991

Glutamine metabolism in a holostean (Amia calva) and teleost fish (Salvelinus namaycush).

Amino acid metabolism was examined in mitochondria from the lateral red muscle of a teleost (lake char, Salvelinus namaycush) and a nonteleost fish (bowfin, Amia calva). Isolated mitochondria oxidize a wide variety of substrates and have high respiratory control ratios. In both species, glutamine is oxidized more rapidly than any other amino acid. The rate of glutamine oxidation by bowfin mitochondria exceeds that of lake char mitochondria, and the bowfin displays correspondingly higher levels of mitochondrial phosphate-dependent glutaminase. It is suggested that amino acids in general, and glutamine in particular, are important oxidative substrates for nonteleost red muscle. The teleost red muscle, however, may rely on both glutamine and fatty acids as oxidative substrates. It appears that glutamate derived from glutamine is oxidized primarily via glutamate dehydrogenase, whereas exogenous glutamate is oxidized primarily via aspartate aminotransferase. Complete oxidation of glutamine may be accomplished in the absence of other substrates by conversion of glutamine-derived malate to pyruvate via malic enzyme. To assess the relative abilities of various tissues to synthesize and oxidize glutamine, the activities of glutamine synthetase and glutaminase were measured. The results of these studies indicate that the organization of glutamine metabolism of fish differs markedly from that in mammals.

Amino Acids↗
PubMed2002

Exercise-induced immunodepression- plasma glutamine is not the link.

The amino acid glutamine is known to be important for the function of some immune cells in vitro. It has been proposed that the decrease in plasma glutamine concentration in relation to catabolic conditions, including prolonged, exhaustive exercise, results in a lack of glutamine for these cells and may be responsible for the transient immunodepression commonly observed after acute, exhaustive exercise. It has been unclear, however, whether the magnitude of the observed decrease in plasma glutamine concentration would be great enough to compromise the function of immune cells. In fact, intracellular glutamine concentration may not be compromised when plasma levels are decreased postexercise. In addition, a number of recent intervention studies with glutamine feeding demonstrate that, although the plasma concentration of glutamine is kept constant during and after acute, strenuous exercise, glutamine supplementation does not abolish the postexercise decrease in in vitro cellular immunity, including low lymphocyte number, impaired lymphocyte proliferation, impaired natural killer and lymphokine-activated killer cell activity, as well as low production rate and concentration of salivary IgA. It is concluded that, although the glutamine hypothesis may explain immunodepression related to other stressful conditions such as trauma and burn, plasma glutamine concentration is not likely to play a mechanistic role in exercise-induced immunodepression.

Exercise↗
PubMed2001

Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling.

Adipose tissue is a major site for whole-body glutamine synthesis and we are investigating mechanisms and regulation of glutamine transport across the adipocyte membrane. Glutamine transport in adipocytes includes both high- and low-affinity Na+-dependent components (consistent with observed expression of ASCT2 and ATA2/SAT2 transporter mRNAs respectively) and a Na+-independent transport component (consistent with observed expression of LAT1/2 transporter mRNAs). Hypo-osmotic (235 mosmol/kg) swelling of adipocytes transiently stimulated glutamine uptake (180% increase at 0.05 mM glutamine) within 5 mins. Stimulation was blocked by the tyrosine kinase inhibitor genistein and the MAP kinase pathway inhibitors PD98059 and SB203580, but not by wortmannin (PI 3-kinase inhibitor) or rapamycin (mTOR pathway inhibitor). Cell-swelling also stimulated uptake of glucose but not MeAIB (indicating that ASCT2 rather than ATA2 was stimulated by swelling). Insulin (66 nM) treatment for up to 1 h stimulated Na+-dependent glutamine transport and increased adipocyte water space. Activation of the ERK1-2 MAP kinase pathway by cell swelling or insulin may be important for rapid activation of the ASCT2 glutamine transporter in adipocytes. Insulin may also exert a minor additional stimulatory effect on adipocyte glutamine transport indirectly via cell swelling. The mechanisms regulating glutamine transport in adipose tissue are distinct from those in other major sites of glutamine turnover in the body (notably liver and skeletal muscle).

Adipocytes↗
PubMed1996

New insights into the compartmentation of glutamate and glutamine in cultured rat brain astrocytes.

Studies from several groups have provided evidence that glutamate and glutamine are metabolized in different compartments in astrocytes. In the present study we measured the rates of 14CO2 production from U-[14C]glutamate and U-[14C]glutamine, and utilized both substrate competition experiments and the transaminase inhibitor aminooxyacetic acid (AOAA) to obtain more information about the compartmentation of these substrates in cultured rat brain astrocytes. The rates of oxidation of 1 mM glutamine and glutamate were 26.4 +/- 1.4 and 63.0 +/- 7.4 nmol/h/mg protein, respectively. The addition of 1 mM glutamate decreased the rate of oxidation of glutamine to 26.3% of the control rate, demonstrating that glutamate can effectively compete with the oxidation of glutamine by astrocytes. In contrast, the addition of 1 mM glutamine had little or no effect on the rate of oxidation of glutamate by astrocytes, demonstrating that the glutamate produced intracellularly from exogenous glutamine does not dilute the glutamate taken up from the media. The addition of 5 mM AOAA decreased the rate of 14CO2 production from glutamine to 29.2% of the control rate, consistent with earlier studies by our group. The addition of 5 mM AOAA decreased the rate of oxidation of concentrations of glutamate < or = 0.1 mM by approximately 50%, but decreased the oxidation of 0.5-1 mM glutamate by only approximately 20%, demonstrating that a substantial portion of glutamate enters the tricarboxylic acid (TCA) cycle via glutamate dehydrogenase (GDH) rather than transamination, and that as the concentration of glutamate increases the relative proportion entering the TCA cycle via GDH also increases. To determine if the presence of an amino group acceptor (i.e. a ketoacid) would increase the rate of metabolism of glutamate, pyruvate was added in some experiments. Addition of 1 mM pyruvate increased the rate of oxidation of glutamate, and the increase was inhibited by AOAA, consistent with enhanced entry of glutamate into the TCA cycle via transamination in the presence of pyruvate. Enzymatic studies showed that pyruvate increased the activity of mitochondrial aspartate aminotransferase (AAT). Overall, the data demonstrate that glutamate formed intracellularly from glutamine enters the TCA cycle primarily via transamination, but does not enter the same TCA cycle compartment as glutamate taken up from the extracellular milieu. In contrast, extracellular glutamate enters the TCA cycle in astrocytes via both transamination and GDH, and can compete with, or dilute, the oxidation of glutamate produced intracellularly from glutamine.

Aminooxyacetic Acid↗
PubMed1996

Mass isotopomer study of glutamine oxidation and synthesis in primary culture of astrocytes.

The metabolism of [1, 2-13C2] acetate via the tricarboxylic acid (TCA) cycle leads to the formation of a number of key mass isotopomers of glutamate. The distribution of these isotopomers which is a function of pyruvate carboxylase, pyruvate dehydrogenase and pyruvate recycling was used to determine the relative anaplerotic flux and glutamine oxidation of astrocytes in culture under different substrate conditions. Combinatory analysis of mass isotopomers formed from the condensation of labeled oxaloacetate with labeled acetyl-CoA was used to determine precursor enrichment and fractional glutamine synthesis. When glucose or glutamine was supplied in the medium, the effective anaplerotic flux (Y') was about 1.5 times that of the TCA cycle flux. Under substrate-limiting conditions, Y' and glutamine synthesis was significantly reduced. A unique feature of the use of [1, 2-13C2] acetate in this study is the formation of singly labeled isotopomer of glutamine in the C4 or C5 position when glutamine is irreversibly loss in net oxidation. We observed very little [4-13C] or [5-13C] glutamine either because of the lack of pyruvate recycling or the lack of pyruvate dehydrogenase activity. The lack of 13C recycling to the C4 and C5 position of glutamine suggests that less than 10% of the glutamine is oxidized into astrocytes for energy production. Therefore, glutamine is not a major energy substrate for astrocytes in culture.

Astrocytes↗
PubMed1984

Renal recovery from metabolic acidosis in the rat: no role for glutamine synthetase.

The role of renal glutamine synthesis for the rapid decrease in renal ammoniagenesis occurring early in the recovery phase (24 h) of metabolic acidosis was studied in rats. L-Methionine-DL-sulfoximine (MSO), an irreversible inhibitor of glutamine synthetase, depressed the renal enzyme activity by 50% but did not impair the recovery from acidosis. Since extrarenal glutamine synthesis was decreased by this manoeuvre with lowering of blood glutamine, an intravenous load of L-glutamine sufficient to elevate blood concentration to 1 mM was superimposed on the MSO treatment. The glutamine load did not increase the ammoniuria. Infusion of glutamine alone to rats recovering from metabolic acidosis for 12-24 h did not change their ammoniuria. In contrast, glutamine administration together with HCl produced a marked ammoniuric response in rats recovering from acidosis. Conversely, the administration of bicarbonate to chronically acidotic rats acutely depressed renal ammonia production. It is concluded that glutamine synthetase activity is probably not required for recovery from metabolic acidosis, and that the post-acidosis alkaline rebound occurring in the rat may play a direct role in suppressing the ammoniagenic pathway either by drastic reduction in mitochondrial permeability for glutamine or acute inhibition of intramitochondrial deamidation of this amino acid.

Acidosis↗
PubMedDate not supplied

Is muscle protein turnover regulated by intracellular glutamine during sepsis?

BACKGROUND: Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. It is not known if this is a causal or coincidental relationship. We tested the hypothesis that muscle protein turnover rates are directly regulated by glutamine. METHODS: Paired extensor digitorum longus muscles from nonseptic (sham-operated) and septic rats (16 hours after cecal ligation and puncture) were incubated in the absence or presence of 15 mmol glutamine/L. The effect of glutamine was tested in unsupplemented medium or in medium containing 1 mU/mL of insulin or a mixture of amino acids at normal plasma concentrations. Protein synthesis was measured as incorporation of 14C-phenylalanine into protein; total and myofibrillar protein breakdown was determined by measuring tyrosine and 3-methylhistidine, respectively. RESULTS: Muscles accumulated intracellular glutamine well above normal concentrations in the presence of 15 mmol glutamine/L. In spite of this, protein synthesis was not affected by glutamine, neither when muscles were incubated in unsupplemented medium nor in medium containing insulin or amino acid mixture. Total protein breakdown was not influenced by glutamine when muscles were incubated in unsupplemented medium or with insulin but was reduced by glutamine in the presence of an amino acid mixture. Myofibrillar protein breakdown was unaffected by glutamine in unsupplemented medium and in medium containing insulin but was increased by glutamine in the presence of amino acid mixture. CONCLUSION: Reduced muscle protein synthesis and increased myofibrillar protein breakdown during sepsis are probably not caused by the low intracellular glutamine levels noticed in this condition.

Amino Acids↗
PubMedDate not supplied

Isocaloric glutamine-free diet and the morphology and function of rat small intestine.

BACKGROUND: The importance of L-glutamine as metabolic fuel for enterocytes and its role in prevention of mucosal atrophy during total parenteral nutrition is well documented. No data are available to date that document whether a glutamine-free complete enteral diet, requiring full energy expenditure for hydrolysis and absorption, is associated with changes in the morphology and function of the small intestine. Our aim was to examine the effect of such a diet during a 4-week period on the morphology and function of the small intestine of rats. METHODS: Three isocaloric solid rat food, containing 0%, 4%, and 8% of glutamate, respectively, were fed to three groups of rats. On the 7th and 28th days the morphology of the jejunum, the subcellular structure of enterocytes on transmission electron microscopy, enzyme activities, blood, and muscle glutamine were examined and compared in the three groups. RESULTS: The rats on the glutamine-free diet had significantly lower mucosal wet weight, protein and DNA content, and number of intraepithelial lymphocytes on the 7th day, whereas the number of mitoses in the Lieberkuhn's crypts was significantly less on the 28th day. The height of the enterocytes and villi was 20% higher on average in the glutamine-free group. Electron microscopy revealed either early (swelling of cristae) or terminal (swelling of matrix) mitochondrial degenerative changes, homogenization of apical cytoplasm, and degeneration and fragmentation of microvilli with loss of their rootlets. The Na+, K(+)-ATPase activity was markedly decreased in the glutamine-free group compared with that of the other groups, most likely because of a diminished energy supply. Among brush border membrane enzymes, lactase activity decreased markedly (p < .05) in the first week. The glutamine-free diet resulted in an increase of the lung glutamine synthetase activity and decrease in muscle glutamine content by the 28th day of the diet. CONCLUSIONS: Our study shows for the first time that a complete enteral diet, deficient only in glutamine, is associated with significant early morphologic and functional changes in the small intestine. The precise effect on intracellular events and the time of onset of these changes needs to be clarified in the future.

Animals↗
PubMedDate not supplied

Glutamine content of protein and peptide-based enteral products.

BACKGROUND: Glutamine is a conditionally essential amino acid for patients with severe catabolic illness, intestinal dysfunction, or immunodeficiency syndromes. Glutamine is a natural component in many enteral preparations, yet lacking methodology hampers its quantitative determination in dietary products. OBJECTIVE: The present study was assigned to assess glutamine contents in selected enteral products by using a newly developed method enabling the assessment of protein/peptide bound glutamine. METHODS: Fourteen commercially available enteral diets (10 protein based and 4 peptide based) were investigated. After removal of interfering fat and carbohydrates, the nitrogen content of the purified preparations was determined by chemiluminescence and protein/peptide bound glutamine was assessed using a three-step procedure; by using a novel prehydrolysis derivatization technique with bis(1,1-trifluoroacetoxy)iodobenzene, glutamine is converted to acid stable diaminobutyric acid. The derivatives are hydrolyzed with a new microwave technology, and subsequently the amino acid composition is determined by reversed phase-high-performance liquid chromatography after dansyl-chloride derivatization. RESULTS: The content in the protein-based preparations varied between 5.2 and 8.1 g/16 g nitrogen. In the peptide-based products, considerably lower glutamine contents were measured (1.3 to 5.6 g/16 g nitrogen). CONCLUSION: In the present study, we report for the first time glutamine contents in ready to use enteral products. The daily amount might be satisfactory for healthy individuals but probably not sufficient for the adequate support of the stressed patient. Reliable assessment of glutamine in enteral formulae is a prerequisite t perform clinical studies investigating glutamine requirements in the catabolic state.

Aminobutyrates↗
PubMedDate not supplied

Glutamine transport and human hepatocellular transformation.

Among other functions, the liver serves to regulate both glucose and nitrogen economy in the body, and in humans, the amino acid glutamine is a major gluconeogenic substrate and the primary extrahepatic ammonia shuttle. Accordingly, the liver acinus possesses a unique heterogeneous metabolic architecture suited to carry out these functions with glutamine-consuming urea cycle and gluconeogenic enzymes in the periportal hepatocytes and a high capacity for glutamine synthesis in the perivenous hepatocytes, resulting in net glutamine balance across the hepatic bed under most conditions. Cytoplasmic levels of glutamine are significantly governed by the activity of the System N transporter in the plasma membrane of parenchymal cells; in this capacity, this glutamine carrier has been shown to represent a rate-limiting step in metabolism via glutaminase. The unique properties of System N allow it to rapidly adapt in support of the dynamic demands of whole body ammonia and glucose homeostasis. In contrast to System N in normal hepatocytes, human hepatoma cells take up glutamine at rates several-fold faster through a broad-specificity higher affinity transporter with characteristics of System ASC or B0. It is currently hypothesized that the expression of this high activity carrier by hepatoma cells combined with accelerated metabolism and tumor-induced derangements in hepatocellular architecture result in net glutamine consumption, and may underlie the diminished plasma glutamine levels observed in patients with hepatocellular carcinoma (HCC). The transport of glutamine through System ASC has been shown to regulate growth in some human hepatoma cells, which suggests this transporter may warrant consideration as a therapeutic target for HCC.

Biological Transport↗
PubMed2002

Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study.

Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28-30 wk; birth weight, 820-1610 g) receiving parenteral nutrition supplying 1.5 g x kg(-1) x d(-1) amino acids and approximately 60 nonprotein kcal x kg(-1) x d(-1) were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g x kg(-1) x d(-1); glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH(13)CO(3) to assess the recovery of (13)C in breath, immediately followed by a 3-h L-[1-(13)C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 +/- 94 versus 503 +/- 83 microM, mean +/- SD; p < 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (-16%, p < 0.05) and leucine oxidation (-35%, p < 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (-20%, p < 0.05), and 4) no change in protein balance (nonoxidative leucine disposal - leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants.

Breath Tests↗
PubMed2003

The swamp eel Monopterus albus reduces endogenous ammonia production and detoxifies ammonia to glutamine during 144 h of aerial exposure.

The swamp eel Monopterus albus inhabits muddy ponds, swamps, canals and rice fields, where it can burrow within the moist earth during the dry summer season, thus surviving for long periods without water. This study aimed to elucidate the strategies adopted by M. albus to defend against endogenous ammonia toxicity when kept out of water for 144 h (6 days). Like any other fish, M. albus has difficulties in excreting ammonia during aerial exposure. In fact, the rates of ammonia and urea excretions decreased significantly in specimens throughout the 144 h of aerial exposure. At 144 h, the ammonia and urea excretion rates decreased to 20% and 25%, respectively, of the corresponding control values. Consequently, ammonia accumulated to high levels in the tissues and plasma of the experimental specimens. Apparently, M. albus has developed relatively higher ammonia tolerance at the cellular and subcellular levels compared with many other teleost fish. Since the urea concentration in the tissues of specimens exposed to air remained low, urea synthesis was apparently not adopted as a strategy to detoxify endogenous ammonia during 144 h of aerial exposure. Instead, ammonia produced through amino acid catabolism was detoxified to glutamine, leading to the accumulation of glutamine in the body during the first 72 h of aerial exposure. Complementing the increased glutamine formation was a significant increase in glutamine synthetase activity in the liver of specimens exposed to air for 144 h. Formation of glutamine is energetically expensive. It is probably because M. albus remained relatively inactive on land that the reduction in energy demand for locomotory activity facilitated its exploitation of glutamine formation to detoxify endogenous ammonia. There was a slight decrease in the glutamine level in the body of the experimental animals between 72 h and 144 h of aerial exposure, which indicates that glutamine might not be the end product of nitrogen metabolism. In addition, these results suggest that suppression of endogenous ammonia production, possibly through reductions in proteolysis and amino acid catabolism, acts as the major strategy to avoid ammonia intoxication in specimens exposed to air for >/=72 h. It is concluded that glutamine formation and reduction in ammonia production together served as effective strategies to avoid the excessive accumulation of ammonia in the body of M. albus during 144 h of aerial exposure. However, these strategies might not be adequate to sustain the survival of M. albus in the mud for longer periods during drought because ammonia and glutamine concentrations had already built up to high levels in the body of specimens exposed to air for 144 h.

Air↗
PubMed2000

Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation.

OBJECTIVE: To determine the effect of glutamine suspension on mucositis associated with the administration of high-dose preparative regimens for bone marrow transplantation. METHODS: We performed a retrospective analysis of 21 consecutive patients receiving high-dose paclitaxel and melphalan as the preparative regimen for autologous peripheral blood stem-cell transplantation for metastatic breast cancer between January 1997 and December 1997. Glutamine suspension was given as swish-and-swallow administration every four hours around the clock starting day-7, for a total dose of 24 g/d. RESULTS: The group given oral glutamine suspension demonstrated significantly fewer days of mucositis and a lower maximum grade of mucositis. The treatment group also had fewer days of parenteral morphine for pain relief. The group that did not receive glutamine required an average of 5.22 days of patient-controlled analgesia (PCA) morphine; the glutamine group did not require PCA morphine. The total days of narcotic pain relief were decreased in the glutamine group; however, this did not reach statistical significance. Qualitatively, the patients in the glutamine group had less oral ulceration and bleeding, and were able to tolerate liquids sooner than those in the nonglutamine group. Patients tolerated the glutamine suspension well. CONCLUSIONS: This study showed that around-the-clock administration of oral glutamine may decrease both the severity and duration of mucositis associated with high-dose bone marrow transplant preparative regimens. The decrease in severity and duration of mucositis translated into reduced parenteral narcotic use. A prospective, randomized, controlled trial is needed to determine future applications of glutamine in the support of patients undergoing high-dose chemotherapy.

Adult↗
PubMed1987

Renal ammonia production from the nitrogens of glutamine in intact acidotic dogs before and after bicarbonate infusions.

Renal ammonia is produced from the amide nitrogen of glutamine, approximately 33-50%. The remainder derives from the amino nitrogen of glutamine and other non amide sources, probably the amino nitrogens of other amino acids. We investigated the acute effects of acid-base perturbations on ammonia production from amide and non amide nitrogen sources to determine how they interrelate. Infusions of glutamine were given to some intact dogs to vary the renal load. Following an acute alkali challenge to dogs in metabolic acidosis, ammoniagenesis from the amide nitrogens decreased significantly when the presentation of glutamine to the kidney was normal or relatively low, but changed less or even increased when the glutamine load was relatively high. In contrast, ammonia from the non amide sources consistently decreased during acute alkalotic challenge at any glutamine load-high or low. Since decreased glutamine deamination leading to glutamate accumulation is generally associated with decreased deamidation in dogs with normal plasma glutamine concentrations, we explain the discrepancy of deamidation at high glutamine loads to an unmasking of a separate effect on the glutaminase (phosphate-dependent) pathway by the acute acid-base changes. Accordingly, our results indicate more than one influence from acute acid-base changes in vivo on renal ammonia formation, one stimulatory and other inhibitory. Nevertheless, the influence of glutamate removal predominates over the other effect on the phosphate-dependent glutaminase pathway at physiological concentrations of glutamine in the intact dog.

Acidosis↗
PubMed1990

Glutamine uptake and utilization by preimplantation mouse embryos in CZB medium.

At least 71% of CF1 x B6SJLF1/J embryos developed from the 1-cell stage to the blastocyst stage in an optimum glutamine concentration of 1 mM, as long as glucose was present after the first 48 h of culture. Blastocysts raised under these conditions had significantly more cells than did blastocysts raised in CZB medium alone (glutamine present, glucose absent). Embryos raised in vivo accumulated 170-200 fmol glutamine/embryo/h at the unfertilized egg and 1-cell stages with a decline to 145 fmol/embryo/h at the 2-cell stage, followed by sharp increases to 400 and 850 fmol/embryo/h at the 8-cell and blastocyst stages. The presence or absence of glucose in the labelling medium had no effect on glutamine uptake by these embryos. Embryos raised in vitro accumulated 2-3 times more glutamine at stages comparable to those of embryos raised in vivo. In all cases in which 1-cell to blastocyst development in vitro was successful, glucose was present in the culture medium and the incremental uptake of glutamine between the 8-cell stage and the blastocyst stage was approximately 2-fold. This was also the increment for in-vivo raised embryos. When glucose was not present after the first 48 h, the 8-cell to blastocyst glutamine increment was not significant, and development into blastocysts was reduced. The results also show that glutamine can be used as an energy source for the generation of CO2 through the TCA cycle by all stages of preimplantation mouse development, whether raised in vivo or in vitro from the 1-cell stage. Two-cell embryos raised in vivo converted as much as 70% of the glutamine uptake into CO2, consistent with an important role for glutamine in the very earliest stages of preimplantation development. Cultured blastocysts appeared to convert less glutamine and the presence of glucose in the culture medium seemed to inhibit this conversion.

Animals↗
PubMed2004

Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants.

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known. METHODS: We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis. RESULTS: Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation. CONCLUSIONS: Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population.

Dietary Supplements↗