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PubMed1996

Glutamine metabolism and neuropathological disorders in experimental hepatic encephalopathy: effect of transplanted hepatocytes.

BACKGROUND: Physiopathology of hepatic encephalopathy remains unclear. Recent studies have suggested that ammonia would not act by itself but through an increase in glutamine in the brain. We have previously demonstrated that transplantation of syngeneic hepatocytes into the spleen was able to correct both behavioral deficits and plasma amino acid changes observed in portacaval shunted rats. The aim of the present work was to show a correlation between the correction of chronic hepatic encephalopathy by means of intrasplenic hepatocyte transplantation and two parameters, brain glutamine concentration and ultrastructural aspects of astrocytes. METHODS: Inbred male Wistar Furth rats were divided into three groups: sham-operated rats (n = 10), rats subjected to portacaval shunt (n = 10), and rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10). Chronic hepatic encephalopathy was quantified 30 and 60 days after operation by means of nose-poke exploration and spontaneous activity. Pathologic examination and measurement of glutamine concentrations in the corpus striatus and in the cerebral cortex were performed 60 days after operation. RESULTS: Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. After portacaval shunt a significant glutamine increase occurred in the corpus striatus and in the cerebral cortex when compared with sham rats (p < 0.05). Ultrastructural examination showed modification of astrocytes named Alzheimer type II after portacaval shunt. Correction of behavioral abnormalities by means of intrasplenic hepatocyte transplantation was associated with partial correction of striatal glutamine increase and with decrease in astrocyte alterations. Cortex glutamine concentration in portacaval shunt-intrasplenic hepatocyte transplantation group and in portacaval shunt rats did not differ significantly. CONCLUSIONS: These data show that intrasplenic hepatocyte transplantation not only prevents neurologic disorders of hepatic encephalopathy but can also decrease glutamine and ultrastructural alterations in the corpus striatus in an experimental model of chronic liver failure. These data are in favor of the involvement of glutamine in chronic hepatic encephalopathy. These results suggest that intrasplenic hepatocyte transplantation might be of therapeutic interest in chronic liver failure.

Animals↗
PubMed1998

Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma.

BACKGROUND: Infections are an important cause of morbidity and mortality in patients with multiple trauma. Studies in both animals and human beings have suggested that glutamine-enriched nutrition decreases the number of infections. METHODS: Patients with multiple trauma with an expected survival of more than 48 h, and who had an Injury Severity Score of 20 or more, were randomly allocated glutamine supplemented enteral nutrition or a balanced, isonitrogenous, isocaloric enteral-feeding regimen along with usual care. Each patient was assessed every 8 h for infection, the primary endpoint. Data were analysed both per protocol, which included enteral feeding for at least 5 days, and by intention to treat. FINDINGS: 72 patients were enrolled and 60 received enteral feeding (29 glutamine-supplemented) for at least 5 days. Five (17%) of 29 patients in the glutamine-supplemented group had pneumonia compared with 14 (45%) of 31 patients in the control group (p<0.02). Bacteraemia occurred in two (7%) patients in glutamine group and 13 (42%) in the control group (p<0.005). One patient in the glutamine group had sepsis compared with eight (26%) patients in the control group (p<0.02). INTERPRETATION: There was a low frequency of pneumonia, sepsis, and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition. Larger studies are needed to investigate whether glutamine-supplemented enteral nutrition reduces mortality.

Adult↗
PubMedDate not supplied

Glutamine transport in human and rat placenta.

Glutamine plays an important role in fetal nutrition. This study explored the transport of [3H]glutamine into apical and basal predominant membrane vesicles derived from rat and human placenta. Na+-dependent glutamine transport was present in both apical and basal predominant vesicles derived from 20- and, to a lesser degree, 14-day gestation rat placenta. Amino-acid transport systems A, ASC-like, B(o,+) (in apical membrane vesicles) and, perhaps, y+L were involved in Na+-dependent glutamine transport. Na+-dependent glutamine uptake into human placental microvillus and basolateral membrane vesicles also occurred via several distinct transport activities. Glutamine transport via system N was not detected in either rat or human placental preparations. Na+-dependent glutamine transport in the rat was more pronounced in basal as compared to apical membrane vesicles. Conversely, in the human preparations, activity was significantly higher in microvillus as compared to basolateral membrane vesicles. It is concluded that Na+-dependent glutamine transport occurs through a variety of transport agencies in both the rat and human placenta. Transport varies with ontogeny and between species.

Animals↗
PubMed1986

Metabolic alterations associated with proliferation of mitogen-activated lymphocytes and of lymphoblastoid cell lines: evaluation of glucose and glutamine metabolism.

In vitro resting, short-term mitogen stimulated, and proliferating rat thymocytes as well as established human T and B lymphoblastoid cell lines were compared in their capacity to metabolize glucose and glutamine as energy source. Furthermore, the pathways of glutamine metabolism in these cells were studied. Compared with resting thymocytes, glucose metabolism of proliferating thymocytes was 36-fold increased during the incubation; 92% of the amount of glucose utilized was converted into trioses mainly lactate, whereas resting cells metabolized only 38% to trioses. However, the latter oxidized 19% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Rates of glucose uptake and degradation to products by the malignant T lymphoblastoid cell line (Jurkat) were nearly identical with those observed with proliferating rat thymocytes, whereas the benign B lymphoblastoid cell lines (DHg-B-1 and LV-B-1) showed significantly higher rates of glucose metabolism. All three transformed lymphoblastoid cell lines, however, metabolized glucose almost completely to lactate as did the proliferating rat thymocytes. Lymphocytes are able to utilize glutamine with glutamate, aspartate and ammonia being the major end-products. A complete recovery of glutamine carbon in the products was obtained with all cells. Glutamine utilization by incubated proliferating rat thymocytes was 8-fold increased as compared to the resting cells. Again the human T lymphoblastoid cell line showed the same rates of glutamine uptake and conversion into products as did the proliferating rat thymocytes, whereas both B lymphoblastoid cell lines had about 2.5-fold enhanced rates as compared to the T cell line. The results indicate that during lymphocyte proliferation caused by mitogen stimulation as well as by permanent transformation into lymphoblastoid cell lines glucose metabolism is altered not only quantitatively but also qualitatively by changing from partly aerobic to almost complete anaerobic glucose breakdown. Glutamine has been found to be a suitable energy source for lymphocytes. About 75% of the amount of glutamate derived from glutamine entered into the citric acid cycle via the aspartate aminotransferase, and the remaining 25% via the glutamate dehydrogenase reaction. The changes in metabolic rates observed in proliferating as well as in transformed or leukemic lymphocytes appear to be reliable parameters to characterize the state of lymphocyte activation or to evaluate the efficacy of lymphokines.

Animals↗
PubMedDate not supplied

Asymmetry of glutamine transporters in cultured neural cells.

Transfer of glutamine between astrocytes and neurons is an essential part of the glutamate-glutamine cycle in the brain. Transport of glutamine was investigated in primary cultures of astrocytes and neurons and compared to glutamine transport in cell lines with glial and neuronal properties. Glutamine uptake in astrocytes was mainly mediated by general amino acid transporters with properties similar to ASCT2, LAT1, LAT2, SN1 and y(+)LAT2. In cultured neurons, transport activities were detected consistent with the presence of LAT1, LAT2 and y(+)LAT2, but the most prominent activity was a novel Na(+)-dependent glutamine transporter that could be inhibited by D-aspartate. The mRNA for system A isoforms ATA1 and ATA2 was detected in both neurons and astrocytes, but system A activity was only detected in neurons. ASCT2 on the other hand appeared to be astrocyte-specific. The cell lines F98 and 108CC-15, having astroglial and neuronal properties, respectively, expressed sets of glutamine transporters that were unrelated to those of the corresponding primary culture and are thus of limited use as models to study transfer of glutamine between astrocytes and neurons.

Amino Acid Transport Systems↗
PubMed1989

Glucocorticoid and acid-base homeostasis: effects on glutamine metabolism and transport.

The amino acid glutamine serves as a major fuel, powering tubular transport processes and base generation in the kidneys of acidotic animals. Removing the adrenals limits the kidneys' response to an exogenous acid load and impairs the removal rate of glutamine from the blood. Administering glucocorticoid to adrenalectomized (ADX) rats reverses a small net release of glutamine to uptake; similarly, administering an exogenous acid load to ADX rats restores the kidneys to organs of net extraction. Glucocorticoid-induced uptake is substantially less than the filtered glutamine load in contrast to uptake across both the luminal and basolateral surfaces when filtered HCO3- is reduced. Furthermore, mitochondrial glutamine oxidation is glucocorticoid dependent with a distinct impairment exhibited by the ADX acidotic rat kidney. However, combining the effect of reduced filtered HCO3- with glucocorticoid supplementation results in a marked potentiation of glutamine uptake coupled to oxidation. These results are consistent with a proposed proximal tubule cell model in which basolateral glutamine uptake is inversely related to basolateral HCO3- efflux and coupled, in the presence of glucocorticoid, to mitochondrial oxidation. This model of glucocorticoid-induced ammoniagenesis predicts an increased renal work capacity when basolateral transport of a major metabolic fuel, glutamine, is closely coupled to its oxidative metabolism.

Acid-Base Equilibrium↗
PubMedDate not supplied

Infection, multiple organ failure, and survival in the intensive care unit: influence of glutamine-supplemented parenteral nutrition on acquired infection.

OBJECTIVE: We investigated the effect of a glutamine-supplemented parenteral nutrition on intensive-care-acquired infection (ICAI) and its relation to outcome. METHODS: We analyzed new data prospectively collected during a double-blind, randomized, and controlled trial in an adult general intensive care unit previously reported (Nutrition 1997;13:295). Eighty-four patients were randomized to receive glutamine-supplemented total parenteral nutrition or an isonitrogenous, isoenergetic control. Sepsis was present on admission in 71% of the patients. Clinical and microbiological data were collected on all new infective episodes and associated treatment decisions. Data were analyzed blind to the randomization and study outcome. RESULTS: There was no significant difference in the number of patients developing new infections or in the number occurring during the first 5 d. There was a non-significant trend to increased numbers of infections in those patients receiving the control feed for at least 5 d. In these patients the glutamine recipients showed significantly fewer catheter-related infections: 21 versus 12 (P = 0.026). The difference in overall 6-mo mortality was almost completely described by those patients fed for at least 5 d: 9 of 25 versus 18 of 27 using the control nutrition (P = 0.05). Of the deaths in the intensive care unit due to multiple organ failure, 8 of 8 in the glutamine group and 14 of 16 in the control group sustained one or more ICAI and accounted for 38% versus 74%, respectively, of the ICAIs occurring in those patients. In those patients, despite a similar high incidence of colonization with Candida, those receiving glutamine developed fewer Candida infections and none died, whereas six control patients who developed Candida infections died from multiple organ failure (P = 0.02). Survival was not related to the reduced occurrence of the first acquired infection; however, binary logistic regression analysis of glutamine and the incidence of ICAI after starting total parenteral nutrition to outcome showed that only glutamine was significantly associated with improved 6-mo survival (P = 0.027). CONCLUSIONS: In these severely ill patients, parenteral nutrition containing glutamine may not reduce the overall incidence of ICAI, but it may reduce the risk of dying from acquired infections. The improved survival seen at 6 mo appeared related mostly to reduced mortality in the intensive care unit from multiple organ failure in those patients in whom acquired infections are common.

Aged↗
PubMedDate not supplied

Glutamine dipeptides in clinical nutrition.

Glutamine is a conditional indispensable amino acid during stress. However, limited solubility and instability of glutamine prevent its addition to presently available nutritional preparations. To overcome these drawbacks, we propose the dipeptide concept by which stable and highly soluble synthetic glutamine containing dipeptides are used. The synthetic dipeptides fulfill all chemical/physical properties to be considered as parenteral substrates. Numerous experimental studies show rapid clearance of parenteral supplied glutamine containing dipeptides without accumulation in tissues; the loss via the urine being inconsequential. Differences related to the dipeptide structure are not observed. There is overwhelming evidence existent that a nutritional support with supplemental glutamine dipeptide positively influences nitrogen excretion, immune status, gut integrity, morbidity, rehabilitation and outcome. Consequently, omission of glutamine from conventional TPN and its subsequent administration should be considered as a replacement of a deficiency rather than a supplementation. It might thus be conceivable that the beneficial effects observed with glutamine nutrition are simply a correction of disadvantages produced by an inadequacy of conventional amino acid solutions. The availability of stable glutamine containing preparations will certainly facilitate an adequate amino acid nutrition in routine clinical setting during episodes of stress and malnutrition.

Animals↗
PubMedDate not supplied

Outcome of critically ill patients after supplementation with glutamine.

Glutamine has many important metabolic roles that may protect or promote tissue integrity and enhance the immune system. The normal abundance of glutamine has meant that it has not been considered necessary to include glutamine in traditional parenteral feeds. However, low plasma and tissue levels of glutamine (Gln) in the critically ill suggest that demand may exceed endogenous supply. A relative deficiency of glutamine in such patients could compromise recovery, result in prolonged illness, and an increase in late mortality. The few percent of the most critically ill intensive care patients who are unable to tolerate enteral nutrition are especially at risk since they have increased demands for glutamine yet lack an exogenous supply. Such patients undergo considerable skeletal muscle wasting compromising glutamine supply further. In a prospective, randomised double blind clinical study of 84 patients with a high mortality due to multiple organ failure requiring parenteral feeding a significant improvement in six-month survival was observed in the group supplemented with glutamine 24/42 versus isonitrogenous, isoenergetic control 14/42, P = 0.049.

Critical Illness↗
PubMedDate not supplied

Prevention of mucosal atrophy: role of glutamine and caspases in apoptosis in intestinal epithelial cells.

Glutamine starvation induces apoptosis in enterocytes; therefore glutamine is important in the maintenance of gut mucosal homeostasis. However, the molecular mechanisms are unknown. The caspase family of proteases constitutes the molecular machinery that drives apoptosis. Caspases are selectively activated in a stimulus-specific and tissue-specific fashion. The aims of this study were to (1) identify specific caspases activated by glutamine starvation and (2) determine whether a general caspase inhibitor blocks glutamine starvation-induced apoptosis in intestinal epithelial cells. Rat intestinal epithelial (RIE-1) cells were deprived of glutamine. Specific caspase activation was measured using fluorogenic substrate assay. Apoptosis was quantified by DNA fragmentation and Hoechst nuclear staining. Glutamine starvation of RIE-1 cells resulted in the time-dependent activation of caspases 3 (10 hours) and 2 (18 hours), and the induction of DNA fragmentation (12 hours). Caspases 1 and 8 remained inactive ZVAD-fluoromethyl ketone, a general caspase inhibitor, completely blocked glutamine starvation-induced caspase activation, DNA fragmentation, and nuclear condensation. These results indicate that glutamine starvation selectively activates specific caspases, which leads to the induction of apoptosis in RIE-1 cells. Furthermore, inhibition of caspase activity blocked the induction of apoptosis, suggesting that caspases are potential molecular targets to attenuate apoptotic responses in the gut.

Amino Acid Chloromethyl Ketones↗
PubMed2002

Glutamine uptake and metabolism to N-acetylaspartylglutamate (NAAG) by crayfish axons and glia.

We have proposed that N-acetylaspartylglutamate (NAAG) or its hydrolytic product glutamate, is a chemical signaling agent between axons and periaxonal glia at non-synaptic sites in crayfish nerves, and that glutamine is a probable precursor for replenishing the releasable pool of NAAG. We report here, that crayfish central nerve fibers synthesize NAAG from exogenous glutamine. Cellular accumulation of radiolabel during in vitro incubation of desheathed cephalothoracic nerve bundles with [3H]glutamine was 74% Na(+)-independent. The Na(+)-independent transport was temperature-sensitive, linear with time for at least 4 h, saturable between 2.5 and 10 mM L-glutamine, and blocked by neutral amino acids and analogs that inhibit mammalian glutamine transport. Radiolabeled glutamine was taken up and metabolized by both axons and glia to glutamate and NAAG, and a significant fraction of these products effluxed from the cells. Both the metabolism and release of radiolabeled glutamine was influenced by extracellular Na(+). The uptake and conversion of glutamine to glutamate and NAAG by axons provides a possible mechanism for recycling and formation of the axon-to-glia signaling agent(s).

Amino Acids↗
PubMed1998

Characteristics of L-glutamine transport by lactating mammary tissue.

The transport of L-glutamine by the lactating rat mammary gland has been investigated using rat mammary tissue explants and the in situ perfused rat mammary gland. L-glutamine uptake by both explants and the perfused mammary gland was via both Na(+)-dependent and Na(+)-independent pathways. It appeared that these pathways are situated on the blood-facing aspect of the mammary gland. L-glutamine uptake by both mammary preparations was markedly inhibited by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid in the absence of external Na+. This is consistent with L-glutamine uptake via system L. The Na(+)-dependent component(s) of L-glutamine uptake remains to be precisely identified. However, system A can be ruled out on the basis that L-glutamine was not inhibited by (methylamino)isobutyric acid. Mammary tissue concentrates L-glutamine with respect to both milk and plasma: we suggest that the Na(+)-dependent component(s) of L-glutamine uptake is responsible for generating the intracellular to extracellular concentration gradient.

Animals↗
PubMedDate not supplied

Neurochemical signatures revealed by glutamine labeling in the chicken retina.

Postembedding immunocytochemistry was used to determine the retinal distribution of the amino acid glutamine, and characterize amino acid signatures in the avian retinal ganglion cell layer. Glutamine is a potential precursor of glutamate and some glutamatergic neurons may use this amino acid to sustain production of glutamate for neurotransmission. Ganglion cells, cells in the inner nuclear layer, and some photoreceptors exhibited glutamine immunoreactivity of varying intensity. Ganglion cells demonstrated the highest level of immunoreactivity which indicates either slow glutamine turnover or active maintenance of a large standing glutamine pool relative to other glutamatergic neurons. Müller's cells in the avian retina are involved in glutamate uptake and carbon recycling by the rapid conversion of glutamate to glutamine, thus explaining the low glutamate and high glutamine immunoreactivity found throughout Müller's cells. Most chicken retinal ganglion cells are glutamate (E) and glutamine (Q) immunoreactive but display diverse signatures with presumed functional subsets of cells displaying admixtures of E and Q with GABA (gamma) and/or glycine (G). The four major ganglion cell signatures are (1) EQ; (2) EQ gamma; (3) EQG; and (4) EQ gamma G.

Animals↗
PubMedDate not supplied

Effects of inhibiting glutamine synthetase and blocking glutamate uptake on b-wave generation in the isolated rat retina.

The purpose of the present experiments was to evaluate the contribution of the glutamate-glutamine cycle in retinal glial (Müller) cells to photoreceptor cell synaptic transmission. Dark-adapted isolated rat retinas were superfused with oxygenated bicarbonate-buffered media. Recordings were made of the b-wave of the electroretinogram as a measure of light-induced photoreceptor to ON-bipolar neuron transmission. L-methionine sulfoximine (1-10 mM) was added to superfusion media to inhibit glutamine synthetase, a Müller cell specific enzyme, by more than 99% within 5-10 min, thereby disrupting the conversion of glutamate to glutamine in the Müller cells. Threo-hydroxyaspartic acid and D-aspartate were used to block glutamate transporters. The amplitude of the b-wave was well maintained for 1-2 h provided 0.25 mM glutamate or 0.25 mM glutamine was included in the media. Without exogenous glutamate or glutamine the amplitude of the b-wave declined by about 70% within 1 h. Inhibition of glutamate transporters led to a rapid (2-5 min) reversible loss of the b-wave in the presence and absence of the amino acids. In contrast, inhibition of glutamine synthetase did not alter significantly either the amplitude of the b-wave in the presence of glutamate or glutamine or the rate of decline of the b-wave found in the absence of these amino acids. Excellent recovery of the b-wave was found when 0.25 mM glutamate was resupplied to L-methionine sulfoximine-treated retinas. The results suggest that in the isolated rat retina uptake of released glutamate into photoreceptors plays a more important role in transmitter recycling than does uptake of glutamate into Müller cells and its subsequent conversion to glutamine.

ATP-Binding Cassette Transporters↗
PubMed1998

Deamidation of specific glutamine residues from alpha-A crystallin during aging of the human lens.

Although it has been hypothesized that age-dependent deamidation of glutamine and/or asparagine residues may play an important role in the turnover of proteins in vivo, surprisingly little is known concerning the extents of deamidation of biologically important proteins with very long half-lives. Alpha-A crystallin is the most abundant protein of the adult human lens, which contains long-lived proteins in the central fetal-embryonic region that were synthesized before birth of the individual. Peptides, corresponding to tryptic fragments of alpha-A crystallin, were synthesized with either the expected glutamine-6, glutamine-50, and glutamine-147 residues, or deamidated glutamic acid residues at the same positions. These synthetic peptides were used to identify and quantitate the amidated versus deamidated forms of each tryptic fragment of alpha-A crystallin from the fetal-embryonic region of lenses from donors of increasing age up to 64 years old. The results demonstrate that all three glutamine residues are very stable, with glutamine-50 undergoing a maximum of approximately 30% deamidation after 64 years postsynthesis, while glutamine-6 and glutamine-147 undergo no detectable deamidation during the same period of time. Together, these results are consistent with the hypothesis that resistance to age-dependent, nonenzymatic deamidation may be an important prerequisite for the stability of proteins in vivo.

Adult↗
PubMed1999

Role of glutamate receptors and glutamate transporters in the regulation of the glutamate-glutamine cycle in the awake rat.

In the present study we investigate the effects of a specific glutamate reuptake blocker, L-trans-pyrrolidine-3,4-dicarboxylic acid (PDC), on extracellular concentrations of glutamine and glutamate in the striatum of the freely moving rat. Intracerebral infusions of PDC (1, 2 and 4 mM) produced a dose-related increase in extracellular concentrations of glutamate and a dose-related decrease in extracellular concentrations of glutamine. These increases in extracellular glutamate and decreases in extracellular glutamine were significantly correlated. To investigate the involvement of ionotropic glutamate receptors in the decreases of extracellular glutamine produced by PDC, N-methyl-D-aspartate (NMDA) receptor antagonist and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist were used. Perfusion of the NMDA receptor antagonist blocked the decrease of extracellular glutamine but had no effect on the increase of extracellular glutamate, both produced by PDC. Perfusion of the AMPA/kainate receptor antagonist attenuated the increase of extracellular glutamate and not only blocked the decrease of extracellular glutamine but also produced a significant increase of extracellular glutamine. The results reported in this study suggest that both NMDA and AMPA/kainate glutamatergic receptors are involved in the regulation of extracellular glutamine.

ATP-Binding Cassette Transporters↗
PubMed2004

Prophylactic administration of topical glutamine enhances the capability of the rat colon to resist inflammatory damage.

Glutamine is an important nutrient for the GI tract and has been shown to exert a protective effect on the bowel. Nonetheless, in the context of IBD, data demonstrating a therapeutic role for glutamine has been inconclusive. IBD is associated with oxidative stress caused by reactive oxygen species. We aimed to investigate the effect of topical glutamine administration in rats before or after induction of colitis by trinitrobenzenosulfonic acid. In study I glutamine enemas were given beginning 2 days before or on the same day of induction of colitis. Inflammation severity was assessed by macroscopic and microscopic score and tissue myeloperoxidase activity. In study II glutamine enemas were given for 3 days without induction of colitis: mitotic index and colonic crypt length were measured, as well as water-soluble low molecular weight antioxidants and energy-rich phosphate levels (by HPLC). Results showed that glutamine significantly decreased indexes of inflammation when administered before induction of colitis. Glutamine caused an increase in the mitotic index and the levels of water-soluble low molecular weight antioxidants and energy-rich phosphates. We conclude that glutamine exerts a beneficial effect only when administered before induction of colitis, by increasing the resistance of the colonic tissue to inflammatory injury. This effect is probably mediated by increasing the antioxidant capacity and energy level of the tissue.

Adenosine Triphosphate↗
PubMed1981

Luminal and antiluminal transport of glutamine in dog kidney: effect of metabolic acidosis.

We have studied the luminal acid antiluminal transport of glutamine and glutamate with the pulse injection multiple indicator dilution technique in normal dogs and in dogs with acute and chronic acidosis. The single-pass experiments yield estimates of unidirectional influx at each nephron surface. The kidney of normal dogs extracts 57% of the arterial glutamine load; 23% of this extraction is due to luminal reabsorption and 34% to antiluminal uptake from the peritubular circulation. After the total net extraction by the kidney is determined from arteriovenous differences and blood flow measurements, in normal dogs, the net antiluminal flux is calculated to be negative, indicating that at least part of the glutamine reabsorbed is returned to the renal venous circulation across the antiluminal membrane. In acutely acidotic dogs, the situation is similar, but a 30% to 40% fall in renal hemodynamics (blood flow and GFR) is observed with secondary reduction in luminal and antiluminal uptake. In chronically acidotic dogs, the unidirectional luminal and antiluminal uptakes of glutamine are similar to that observed in normal animals, but the calculated efflux across the antiluminal membrane is drastically reduced. These findings suggest that (l) a cellular transport mechanism for glutamine exists at the antiluminal pole of the renal tubule and dominates the luminal uptake process in normal animals; (2) cellular transport of glutamine (luminal and antiluminal) does not play a role in the renal adaptation to metabolic acidosis; (3) the intrarenal utilization of glutamine acts as a metabolic sink for this amino acid, which in turn regulates its net uptake by the kidney; and (4) the total uptake of glutamine limits ammoniagenesis in this species.

Acidosis, Renal Tubular↗