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At least 1,315 records · Page 73Linked to original sources
PubMed1991

L-glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis.

Rotavirus enteritis is the leading cause of diarrhea in infants worldwide. A research priority of the World Health Organization is to develop oral rehydration solutions containing amino acids or other additives that will stimulate intestinal absorption more efficiently than the current glucose-based oral rehydration solutions. Glutamine is the principal metabolic fuel of the small bowel and a putative stimulator of mucosal repair. This report describes the transport response to mucosal L-glutamine following intestinal injury caused by porcine rotavirus. Peak symptoms and mucosal damage were observed 2-7 days after oral rotavirus inoculation. In vitro transport studies of the maximally injured region, the midjejunum (80% reduction in lactase), surprisingly, showed transport responses to L-glutamine (30 mmol/L) and L-alanine (30 mmol/L) that were similar qualitatively and quantitatively to those observed in control tissue. Subsequent application of mucosal D-glucose (30 mmol/L) caused additional stimulation of electrogenic Na+ transport, but the response to glucose was blunted (P less than 0.05) in the infected tissues. Glutamine and alanine enhanced Na+ absorption to a similar degree (2-2.5 muEq.cm-2.h-1), but glutamine stimulated equal amounts of electrogenic and electroneutral NaCl absorption, whereas alanine had no significant effect on net Cl- flux. Glutamine is a potentially useful substrate for investigation in oral rehydration solutions for infant diarrhea.

Alanine↗
PubMed1992

Altered glutamine metabolism in rat portal drained viscera and hindquarter during hyperammonemia.

In normal rats, muscle is the major glutamine releasing organ and gut is the major glutamine consuming organ. It has been suggested that enhanced muscle ammonia detoxification and gut ammonia production occurs during liver insufficiency-induced hyperammonemia. Therefore, ammonia and amino acid fluxes across portal-drained viscera and hindquarter, and muscle concentrations were measured in portacaval shunted and acute liver ischemia rats. Arterial ammonia and most amino acids were increased after portacaval shunting and increased progressively during liver ischemia, but net hindquarter ammonia uptake was not observed. Net hindquarter glutamine efflux was increased during portacaval shunting, but it decreased during liver ischemia, while muscle glutamine concentrations increased. The comparable net portal drained viscera glutamine uptake in normal and portacaval shunted rats changed during liver ischemia from net uptake to release, coinciding with release of most other amino acids. These results cast doubt on the ammonia detoxifying role of muscle during acute liver ischemia-induced hyperammonemia in the rat. The portal drained viscera glutamine release during severe hyperammonemia could be due to intestinal damage.

Amino Acids↗
PubMed1991

The effect of tumour bearing on skeletal muscle glutamine metabolism.

1. The effects of tumour bearing on glutamine metabolism in rat skeletal muscle were examined using the Walker 256 carcinosarcoma. 2. There was a rapid and marked decrease in skeletal muscle glutamine content, which was correlated with the size of the tumour, and a decrease in plasma glutamine concentration. 3. The rate of release of glutamine from EDL muscle in vitro was increased in cachectic, tumour bearing animals, but was unaffected from the soleus muscle of the same animals. 4. It is hypothesized that the increase in the rate of muscle glutamine release during cachexia represents a response of this tissue in order to satisfy the demand for glutamine by the tumour or by cells of the immune system.

Animals↗
PubMed1989

Proton nuclear magnetic resonance studies on glutamine-binding protein from Escherichia coli. Formation of intermolecular and intramolecular hydrogen bonds upon ligand binding.

Proton nuclear magnetic resonance studies have revealed several structural and dynamic properties of the glutamine-binding protein of Escherichia coli. When this protein binds L-glutamine, six low-field, exchangeable proton resonances appear in the region from +5.5 to +10 parts per million downfield from water (or +10.2 to +14.7 parts per million downfield from the methyl proton resonance of 2,2-dimethyl-2-silapentane-5-sulfonate). This suggests that the binding of L-glutamine induces specific conformational changes in the protein molecule, involving the formation of intermolecular and intramolecular hydrogen bonds between the glutamine-binding protein and L-glutamine, and within the protein molecule. The oxygen atom of the gamma-carbonyl group of L-glutamine is likely to be involved in the formation of an intermolecular hydrogen bond between the ligand and the binding protein. We have shown that at least one phenylalanine and one methyl-containing residue are spatially close to this intermolecular hydrogen-bonded proton. The intermolecular and intramolecular hydrogen-bonded protons of the ligand-protein complex undergo solvent exchange. The local conformations around these intermolecular and intramolecular hydrogen bonds are quite stable when subjected to pH and temperature variations. From these results, the utility of proton nuclear magnetic resonance spectroscopy for investigating such binding proteins has been shown, and a picture of the ligand-binding process can be drawn.

Amides↗
PubMed1990

Oral glutamine reduces bacterial translocation following abdominal radiation.

The effect of dietary glutamine on bacterial translocation was studied in rats following administration of a single dose of abdominal radiation (1000 rad) that causes a reproducible mucosal injury and results in a high incidence of culture-positive mesenteric lymph nodes after radiation (XRT). Following XRT, rats received only the amino acid glutamine (3%, +GLN) in their drinking water or a control nonessential amino acid (glycine, -GLN). Diets were isonitrogenous and isovolumetric. Four days after XRT, rats were anesthetized and a laparotomy was performed. Mesenteric lymph nodes were sterilely excised and cultured. Arterial blood was also obtained for whole blood glutamine determination. Control rats received no XRT but received identical diets. In XRT rats who received the GLN-free diet, the incidence of culture-positive mesenteric lymph nodes was 89% (eight of nine rats) while in the radiated rats receiving the GLN-enriched diet, the incidence fell to 20% (P less than 0.05). In non-radiated control rats receiving GLN-enriched and GLN-depleted diets for 4 days, bacterial translocation occurred in zero of eight and one of eight rats, respectively (NS). Provision of glutamine to XRT rats resulted in higher blood levels of glutamine (408 +/- 25 microM in XRT +GLN vs 311 +/- 19 microM in XRT -GLN, P less than 0.05). In addition, provision of GLN maintained mucosal mass and reduced weight loss (P less than 0.05). The data lend further support to the hypothesis that glutamine helps maintain the gut mucosal barrier and thereby decreases the incidence of bacterial translocation following bowel injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1991

The effects of endotoxin on glutamine transport by pulmonary artery endothelial cells.

The effects of endotoxin on glutamine transport by cultured pulmonary artery endothelial cells (PAECs) were studied in order to gain further insight into the regulation of the altered lung glutamine metabolism that characterizes severe infection. Incubation of PAECs with endotoxin (1 micrograms/ml) resulted in a significant increase in System ASC-mediated glutamine transport which did not occur for 8 hr and was maximal after 12 hr of exposure. Kinetic studies indicated that the increase in carrier-mediated activity was not due to a change in Km (101 +/- 6 microM in controls vs 97 +/- 4 microM in endotoxin-treated cells, P = NS), but rather to a 73% increase in Vmax (840 +/- 60 pmole/mg protein/30 sec in controls vs 1450 +/- 80 in endotoxin-treated cells, P less than 0.001). The increase in glutamine uptake by PAECs was completely blocked by actinomycin D and cycloheximide, indicating that the accelerated glutamine transport was most probably due to an increase in transporter synthesis. Endotoxin stimulates glutamine uptake by PAECs, either directly or indirectly, an adaptive response which may be necessary to support cellular metabolism, structure, and function.

Animals↗
PubMed1992

The early response of the jejunal brush border glutamine transporter to endotoxemia.

The early effects of endotoxin (4 hr after a single dose of Escherichia coli LPS, 7.5 mg/kg) on L-glutamine (GLN) transport across the jejunal brush border of rats were studied. Jejunal brush border membrane vesicles (BBMVs) were prepared by a Mg2+ aggregation/differential centrifugation technique. Vesicle purity and integrity were confirmed by a 15-fold enrichment of brush border marker enzymes, osmotic activity, transport overshoots in the presence of sodium, and similar 1- and 2-hr equilibrium values. L-[3H]GLN transport in jejunal BBMVs was measured by a millipore filtration technique. Na(+)-dependent glutamine transport, which accounted for greater than 80% of total transport, was increased twofold in BBMVs from endotoxin-treated rats (67 +/- 5 pmole/mg protein/15 sec vs 38 +/- 3, P less than 0.01). Endotoxin treatment did not alter the activity of the Na(+)-independent carrier. Simultaneously, intestinal extraction of glutamine from the bloodstream fell by 56% (15.1 +/- 2.3% in controls vs 6.6 +/- 1.3% in endotoxin-treated rats, P less than 0.01). This reduction in the uptake of circulating glutamine could not be accounted for by a fall in the arterial concentration. Thus, soon after endotoxemia brush border glutamine uptake is increased while consumption of glutamine across the basolateral membrane is decreased. This increased uptake may support protein synthesis and may provide a biochemical rationale for the use of early enteral nutrition after the onset of critical illness.

Animals↗
PubMed1989

Influence of molecular structure and plasma hydrolysis on the metabolism of glutamine-containing dipeptides in humans.

Glutamine-containing dipeptides may serve as a source of glutamine in parenteral nutrition solutions. To study the metabolism of glycyl-L-glutamine (gly-gln) and L-alanyl-L-glutamine (ala-gln) bolus injections of both dipeptides (0.1 mmol/kg within 40 seconds) were performed in five healthy male volunteers. Furthermore, plasma hydrolase activity against both peptides was tested by in vitro incubation. Both peptides were rapidly cleared from plasma after injection; however clearance was significantly greater for ala-gln than for gly-gln (1,595 +/- 124 v 507 +/- 14 mL/min). Arterial concentrations of constituent amino acids rose after peptide injection, indicating hydrolysis of the peptides. Glutamine concentration, for example, rose from 573 +/- 29 to a maximum of 718 +/- 34 mumol/L after gly-gln and from 570 +/- 15 to 900 +/- 53 mumol/L after ala-gln injection. Both peptides were hydrolyzed by plasma hydrolases during in vitro incubation. Hydrolysis was greater for ala-gln than for gly-gln. Half-lives of ala-gln and gly-gln were 46 +/- 3 and 553 +/- 160 minutes, respectively. For both peptides, plasma hydrolysis was too low to contribute significantly to in vivo clearance. Our results indicate that gly-gln and ala-gln are suitable sources for glutamine in parenteral nutrition solutions. Furthermore, plasma hydrolases do not play a significant role in peptide metabolism. Both peptides therefore appear to be primarily metabolized via extracellular hydrolysis, presumably by hydrolases on the cell membranes and consecutive uptake of the liberated amino acid residues.

Adult↗
PubMed1989

Availability of glutamine supplied intravenously as alanylglutamine.

In this review, new knowledge about the potential use of glutamine containing dipeptides as substrates in the frame of parenteral nutrition is presented. Using chemical and biotechnological methods, the stable and highly soluble peptide L-alanyl-L-glutamine (Ala-Gln) can be synthesized in high yields. Studies in experimental rats and dogs demonstrate the effective utilization of intravenously supplied Ala-Gln and the rapid provision of free glutamine for maintenance of the intracellular muscle-free glutamine pool in catabolic situations. Subsequent studies in healthy volunteers provide firm evidence that the infused Ala-Gln is rapidly eliminated from plasma (t1/2:3.8 minutes), associated by a prompt equimolar increase in the concentrations of free alanine and glutamine. Bolus injection and continuous infusion of the peptide was not accompanied by any side effects, and no complaints by the subjects were noted. These results may indicate a safe and efficient use of Ala-Gln as source of free glutamine in parenteral nutrition.

Animals↗
PubMed1989

Influence of alanylglutamine infusion on gastrointestinal glutamine and alanine metabolism in anesthetized dogs.

In this study we administered an infusion of alanylglutamine (10 mumol/kg.min) for 60 minutes to postoperative anaesthetized dogs with catheters placed in the portal and hepatic veins. Arterial plasma levels of alanylglutamine were 83 +/- 27 mumol/L 20 minutes after the onset of the infusion and remained constant throughout the infusion period. Plasma levels of glutamine and alanine approximately doubled compared with preinfusion levels, indicating a release of these amino acids from the dipeptide. The halflife of alanylglutamine, calculated after bolus injection of 2 g, was 1.7 +/- 0.5 minutes. Alanylglutamine was extracted from the liver and the gut (0.9 +/- 0.3 and 0.5 +/- 0.1 mumol/kg.min, respectively). In the basal period (without infusion of alanylglutamine), a glutamine uptake by the liver and the intestine was found. Alanine was taken up by the liver and released from the gut. The infusion of alanylglutamine significantly increased the hepatic uptake of glutamine and alanine (from 0.8 +/- 0.2 to 3.8 +/- 0.6 and from 3.0 +/- 0.4 to 7.5 +/- 0.7 mumol/kg.min respectively; P less than .01) and did not significantly change the intestinal uptake of glutamine and the release of alanine. We conclude that the infusion of alanylglutamine markedly influences the hepatic metabolism of glutamine and alanine, probably via the increased arterial and portal levels of glutamine and alanine.

Alanine↗
PubMed1982

Glutamine requirements for purine metabolism in leukemic lymphoblasts.

The two pathways of purine metabolism that include glutamine-dependent reactions, purine synthesis de novo and guanine nucleotide synthesis, were studied in cultured lymphoblasts derived from patients with T cell (JM), B cell (BALL) or null cell (NALL) acute lymphoblastic leukemia (ALL). When glutamine was omitted from the incubation medium, purine synthesis de novo, measured by the incorporation of 14C-formate into purine compounds, was depressed to barely measurable rates in BALL and NALL cells, but proceeded at moderate though reduced rates in JM cells, when compared to synthesis in the presence of 2 mM glutamine. Similarly, the incorporation of 14C-hypoxanthine into guanine nucleotides was arrested at the glutamine-requiring XMP-aminase reaction in the BALL and NALL lines but not in the JM line, when exogenous glutamine was absent. The data suggest that glutamine deprivation, whether by omission from the culture medium in vitro or by glutaminase treatment in vivo, will have more profound biochemical consequences in B and null cell-derived ALL than in T All.

B-Lymphocytes↗
PubMed1992

Regulation of the glutamine content of astrocytes by cAMP and hydrocortisone: effect of pH.

It was reported recently that the glutamine content of astrocytes incubated with glutamate and ammonium is steeply dependent on the pH of the solution. The present study shows that pretreatment of astrocytes with dibutyryl cAMP or with hydrocortisone, conditions that induce glutamine synthetase activity, increased glutamine content 2.4-fold and 5.3-fold, respectively. Nevertheless, a shift of pH from 7.4 to 7.8 increased glutamine content further by 2.7-fold and 3.0-fold, respectively. The net rates of uptake of glutamate and export of glutamine varied narrowly compared to these very large changes in glutamine content.

Animals↗
PubMed1995

Glutamate and glutamine metabolism in cultured GABAergic neurons studied by 13C NMR spectroscopy may indicate compartmentation and mitochondrial heterogeneity.

Primary cultures of mouse cerebral cortical neurons were incubated for 3 h with 250 microM [U-13C]glutamate or 250 microM [U-13C]glutamine and 6 mM glucose. 13C NMR spectra of cell extracts exhibited distinct multiplets for glutamate, aspartate and GABA. Incorporation of label into aspartate can only occur through the tricarboxylic acid (TCA) cycle, but as demonstrated by formation of the 3,4-13C2-isotopomer of GABA and the 1,2,3-13C3-isotopomer of glutamate, these amino acids were also to some extent derived from this pathway. Formation of the 1,2-13C2-(1J1,2 = 50 Hz) and 3,4-13C2-isotopomer (1J3,4 = 50.9 Hz) in aspartate occurs exclusively when oxaloacetate (containing 12C) is derived from the second turn of the TCA cycle. From [U-13C]glutamine, the 12C containing isotopomers in aspartate accounted for 27% of the total label and from [U-13C]glutamate, it was less than 10%. When [U-13C]glutamine was the precursor, 36% of the labeled glutamate and 52% of the labeled GABA contained 12C incorporated during the first turn of the TCA cycle. These numbers decreased to 15 and 30%, respectively when [U-13C]glutamate was used. Since glutamine must be converted to glutamate before it can enter the TCA cycle as 2-oxoglutarate, appearance of 12C incorporation in aspartate should be identical when [U-13C]glutamate and [U-13C]glutamine was used as substrates. This was, however, not observed which may be indicative of (1) compartmentation of mitochondrial glutamate metabolism or (2) differences in the amount of intramitochondrial glutamate derived from external glutamate or glutamine.

Animals↗
PubMed1978

Activity of nitrogenase and glutamine synthetase in relation to availability of oxygen in continuous cultures of a strain of cowpea Rhizobium sp. supplied with excess ammonium.

In samples from nitrogen-fixing continuous cultures of strain CB756 of the cowpea type rhizobia (Rhizobium sp.), newly fixed NH+4 is in equiblibrium with the medium, from where it is assimilated by the glutamine synthetase/glutamate synthase pathway. In samples from steady state cultures with different degrees of oxygen-limitation, nitrogenase activity was positively correlated with the biosynthetic of glutamine synthetase in cell free extracts. Also, activities in biosynthetic assays were positively correlated with activities in gamma-glutamyl transferase assays containing 60 mM Mg2+. Relative adenylylation of glutamine synthetase was conveniently measured in cell free extracts as the ratio of gamma-glutamyl transferase activities without and with addition of 60 mM Mg2+. Automatic control of oxygen supply was used to facilitate the study of transitions between steady-state continuous cultures with high and low nitrogenase activities. Adenylylation of glutamine synthetase and repression of nitrogenase activity in the presence of excess NH+4, were masked when oxygen strongly limited culture yield. Partial relief of the limitation in cultures supplied with 10 mM NH+4 produced early decline in nitrogenase activity and increase in relative adenylylation of glutamine synthetase. Decreased oxygen supply produced a rapid decline in relative adenylylation, followed by increased nitrogenase activity, supporting the concept that control of nitrogenase synthesis is modulated by glutamine synthetase adenylylation in these bacteria.

Ammonium Sulfate↗
PubMed1983

Lactate, alanine and glutamine metabolism in isolated canine pup liver cells.

The metabolism of lactate, alanine and glutamine was studied in isolated canine liver cells. Lactate proved a better gluconeogenic precursor than alanine and glutamine. Glucose was synthesized at similar rates from both amino acids and ureogenesis from glutamine was double that from alanine. As in isolated rat liver cells, glucose and urea represented the main carbon and nitrogenous end-products of lactate, alanine and glutamine metabolism. Taken with the known levels of hepatic uptake of glutamine and alanine, these findings suggest that in the fasted dog, unlike in the fasted rat, glutamine and not alanine is the main transporter of nitrogen and carbon from muscle to liver for urea synthesis and gluconeogenesis.

Alanine↗
PubMed1985

[13N]Ammonia and L-[amide-13N]glutamine metabolism in glutaminase-sensitive and glutaminase-resistant murine tumors.

The short-term metabolic fate of labeled nitrogen derived from [13N]ammonia or from L-[amide-13N]glutamine was determined in murine tumors known to be resistant (Ridgeway Osteogenic Sarcoma (ROS] or sensitive (Sarcoma-180 (S-180)) to glutaminase therapy. At 5 min after intraperitoneal injection of [13N]ammonia or of L-[amide-13N]glutamine, only about 0.7% of the label recovered in both tumors was in protein and nucleic acid. After [13N]ammonia administration, most of the label (over 80%) was in a metabolized form; a large portion of this metabolized label (50-57%) was in the urea fraction with a smaller amount in glutamine (37-42%). The major short-term fate of label derived from L-[amide-13N]glutamine was incorporation into components of the urea cycle with smaller amounts in the acidic metabolites and in acidic amino acids. No labeled urea was found during in vitro studies in which S-180 tumor slices were incubated with [13N]ammonia, suggesting that the [13N]urea formed in the tumor in the in vivo experiments was not due to de novo synthesis through carbamyl phosphate in the tumor. Both tumors exhibited very low glutamine synthetase activity. Following glutaminase treatment, glutamine synthetase and gamma-glutamyltransferase activities, while remaining low, increased in the resistant tumor but not in the sensitive tumor; this increase may be related to the insensitivity of the ROS tumor toward glutaminase treatment.

Amino Acids↗
PubMed1991

Concomitant synthesis and degradation of glutamine in isolated rabbit kidney tubules.

When rabbit kidney tubules were incubated with 1 mM [1-14C]glutamine as substrate, a release of 14CO2 together with a net production of glutamine were observed. That glutamine utilization was masked by higher rates of concomitant glutamine synthesis was demonstrated by: (i) inhibiting glutamine synthesis; and (ii) measuring the specific radioactivity of [1-14C]glutamine which fell during incubation.

Animals↗
PubMed1995

Regulation of glutamine and glucose metabolism by cell volume in lymphocytes and macrophages.

The effects of osmotically and sucrose-induced cell volume changes on glutamine and glucose metabolism were investigated in rat lymphocytes and macrophages incubated for 10-60 min at 37 degrees C in Krebs-Henseleit bicarbonate buffer (pH 7.4). Decreasing extracellular osmolarity from 336 to 286 mOsmol by decreasing medium NaCl from 119 to 94 mM increased cell volume and the rates of glutamine metabolism and glycolysis in both cell types. Conversely, increasing extracellular osmolarity from 286 to 386 mOsmol by the addition of 50 and 100 mM D-mannitol progressively decreased both cell volume and the rates of glutamine and glucose metabolism in lymphocytes and macrophages. At the same medium osmolarity of 336 mOsmol, the rates of glutamine metabolism and glycolysis were greater with the addition of 50 mM sucrose than with that of 25 mM NaCl. The sucrose-induced increase in cell volume, which is due to the uptake of sucrose by lymphocytes and macrophages via pinocytosis, is associated with enhanced rates of glutamine metabolism and glycolysis. Our findings suggest that cell volume change may be a hitherto unrecognized mechanism for regulating metabolism in lymphocytes and macrophages. The enhanced glutamine and glucose metabolism in these cells in response to mitogenic stimulation or immunological activation may result, at least in part, from the concomitant increase in cell volume.

Animals↗