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PubMed1986

Hepatic enzymes of glutamine and ureagenesis in metabolic acidosis.

The activities of key glutamine and urea cycle enzymes were assayed in liver homogenates from control and chronically acidotic rats and compared with citrulline and urea productions by isolated mitochondria and intact liver slices, respectively. Glutamine-dependent urea and citrulline synthesis were increased significantly in isolated mitochondria and in liver slices; the activities of carbamoyl phosphate synthetase and arginase were unchanged and increased, respectively. Glutamine was not a precursor in the carbamoyl phosphate synthetase system, suggesting that the glutamine effect is an indirect one and that glutamine requires prior hydrolysis. Increased mitochondrial citrulline synthesis was associated with enhanced oxygen consumption, suggesting glutamine acts both as a nitrogen and fuel source. Hepatic phosphate-dependent glutaminase was elevated by chronic acidosis. The results indicate that the acidosis-induced reduction in ureagenesis and reversal from glutamine uptake to release observed in vivo are not reflections of corresponding changes in the hepatic enzyme content. Rather, when available, glutamine readily supports ureagenesis, suggesting a close coupling of hepatic glutaminase flux with citrulline synthesis.

Acidosis↗

PubMed2000

[Cellular immunity changes after total parenteral nutrition enriched with glutamine in patients with sepsis and malnutrition].

The influence of glutamine on human immune system is multidirectional but the exact changes still remain unclear. In this study the effect of total parenteral nutrition (TPN) enriched with glutamine on some selected immunological and nutritional parameters was examined in twelve surgical patients with sepsis and malnutrition. The reason for glutamine supplementation was lack of clinical improvement after standard TPN. All patients received TPN enriched with glutamine for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4, CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine administration and two days after (day 12) glutamine withdrawal. Simultaneously some nutritional parameters were assessed. The number and percentage of CD4, CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the same level during observation (with exception in CD4 on day 6, 12 and CD56 on day 4). No significant differences in CD8 and HLA-DR number and percentages were observed after TPN enriched with glutamine. BIA examination revealed on days 2 and 12 significant decrease of total body water and significant increase of body cell mass, intracellular water on day 12. It was correlated with significant higher total lymphocytes count and significantly higher total protein, serum albumin, transferrin, cholesterol and CRP concentration. Results demonstrated that TPN supplemented with glutamine improved rapidly some immunological and nutritional parameters in surgical, malnutrition patients with sepsis.

Adult↗

PubMed2000

Inhibition of muscle glutamine formation in hypercatabolic patients.

Glutamine is synthesized primarily in skeletal muscle, and enables transfer of nitrogen to the liver, as well as serving other functions. There is increasing evidence for beneficial clinical effects of glutamine supplementation in critically ill patients. However, the response of endogenous glutamine formation to severe stress is poorly understood. The rates of net protein balance, leucine oxidative decarboxylation, and alanine and glutamine synthesis de novo were determined in leg skeletal muscle of 20 severely burned patients and 19 normal controls in the post-absorptive state. Patients were studied at 14+/-5 days post-burn, and their mean burn size was 66+/-18% of total body surface area. Methods were based on the leg arteriovenous balance technique in combination with biopsies of the vastus lateralis muscle. In the post-absorptive state, patients with severe burns, as compared with healthy control subjects, exhibited accelerated muscle loss (+150%) (i.e. proteolysis minus synthesis) and leucine oxidative decarboxylation (+117%), and depletion of the intramuscular free glutamine pool (-63%). The average rate of glutamine synthesis de novo was decreased by 48%, whereas net alanine synthesis de novo was increased by 174%, in skeletal muscle of burned patients. In conclusion, in severely hypercatabolic burned patients, muscle glutamine formation was suppressed, whereas alanine was the major vehicle for inter-organ nitrogen transport. These changes account for a decreased glutamine availability during prolonged severe stress.

Adult↗

PubMed2002

Hepatocyte mitochondrial metabolism is inhibited in neonatal rat endotoxaemia: effects of glutamine.

Glutamine has beneficial effects on enterocytes and the immune system in sepsis, but its effects on hepatic metabolism remain unknown. The aim of the present study was to determine the effects of glutamine on hepatocyte energy metabolism under conditions of neonatal endotoxaemia. Suckling Wistar rats were injected intraperitoneally with 200 microg/kg lipopolysaccharide. Oxygen consumption was measured polarographically in hepatocytes respiring on either palmitate (0.5 mM) or palmitate plus glutamine (10 mM). Total hepatocyte oxygen consumption was similar in hepatocytes from control and endotoxic rats, but this was due to a decrease in intramitochondrial and an increase in extramitochondrial oxygen consumption in the cells from endotoxic animals. The addition of glutamine to hepatocytes from endotoxic rats restored intramitochondrial oxygen consumption to control levels. Although glutamine did not reverse the inhibition of the thermogenic proton leak observed in endotoxaemia, it significantly increased oxygen consumption due to mitochondrial ATP synthesis (P=0.03). Glutamine significantly increased the hepatocyte ATP/ADP ratio (P=0.02 compared with hepatocytes from endotoxic rats). Electron microscopy revealed morphological damage to the mitochondria of hepatocytes from endotoxic rats, and a return to a normal appearance with the addition of glutamine. We conclude that glutamine reverses the inhibition of mitochondrial metabolism that is observed in endotoxaemia. The effect is primarily at the level of ATP synthesis.

Adenosine Diphosphate↗

PubMed2003

Enteral alanyl-glutamine supplement promotes intestinal adaptation in rats.

Although parental administration of glutamine promotes intestinal adaptation, it is controversial whether enteral glutamine is effective after small bowel resection. To further evaluate the benefits of enteral supplementation, peptide and amino acid peptide transporter function must be considered. We evaluated the effect of enteral alanyl-glutamine based on the alteration of peptide and amino acid transporter expressions after massive small intestinal resection. Rats underwent 80% proximal intestinal resection. Expression of the glutaminase (GA), amino acid transporter B0 and peptide transporter PepT1 mRNA in the residual intestinal cells was initially examined by Northern blot analysis. Rats with a small bowel received a bolus supplement of glutamine (2.0 g/kg/day) + alanine (1.22 g/kg/day) mixture, alanyl-glutamine (2.972/kg/day) or saline for 3 days from one day before operation. On the 3rd postoperative day (POD) and the 7th POD, residual intestinal tissue was removed, and mucosal parameters were measured. The GA activity and GA mRNA significantly increased on the 1st POD. Although the levels of B0 mRNA gradually decreased, the PepT1 mRNA increased after surgery, and reached 150% of the initial level on the 5th POD. In the rats administered alanyl-glutamine, mucosal wet weight and protein content similarly increased with increasing villus height on the 7th POD. Enteral supplementation with alanyl-glutamine but not glutamine + alanine mixture promotes intestinal adaptation as evidenced by increased peptide transport after intestinal resection.

Alanine↗

PubMed1992

Acute ethanol administration and the metabolism of glutamine by skeletal muscle of the rat: implications for ethanol-induced reductions in protein synthesis.

The effect of acute ethanol administration (75 mmol/kg) on the metabolism of glutamine by skeletal muscle of the rat was studied in order to investigate the hypothesis that the concentration of this amino acid in muscle controls the rate of protein synthesis. Ethanol administration was without effect on the concentration of glutamine in EDL (extensor digitorum longus) and plantaris muscles (Type II fibre-rich muscles), but increased the concentration in soleus muscle (Type I fibre-rich muscle). The rate of release of glutamine was increased from EDL muscle, but unchanged from soleus muscle of treated animals. Ethanol administration was without effect on the maximal activity of glutamine synthetase in both soleus and EDL muscles. It is concluded that changes in the concentration of glutamine in muscle cannot explain the ethanol-induced changes in the rate of protein synthesis. Nevertheless, the increase in the concentration of glutamine in soleus muscle following ethanol administration is of interest and may be mediated via modulation of the glutamine transporter and/or the activity of glutamine synthetase in vivo.

Alanine↗

PubMed2004

[Analysis of the therapeutic effect and the safety of glutamine granules per os in patients with severe burns and trauma].

OBJECTIVE: To observe the therapeutic effect and possible side effects of glutamine granules per os in patients with trauma, burns and major operations. METHODS: Patients inflicted with severe burns, trauma and major operations were enrolled in the study. One hundred and twenty patients were randomly divided into two groups, 60 in control group (C) and 60 in glutamine group (Gln). Randomized double blind and placebo control methods were employed in the study. All the patients in both groups were given diet with equal calories and equal nitrogen content. The patients in Gln group received glutamine granules in dose of 0.5 g.kg(-1).d(-1) orally or by gavage, while those in C group received same dose of placebo (glycine) for 7 days. The changes in the intestinal mucosal barrier function, the protein metabolism, the immune function, hepatic and renal functions, and the incidence of side effects of the medication in both groups of patients were observed and compared before and after the supplementation of glutamine or glycine. RESULTS: The plasma contents of glutamine, proteins and interleukin 2 in both groups were all lower than normal values. But the plasma diamine oxidase (DAO) activity, endotoxin content, intestinal mucosal permeability (urine lactose/mannitol, L/M) and urine excretion of nitrogen increased obviously in both groups. The plasma glutamine concentration in Gln group increased by 38.04% after the administration of Gln for 7 days (P < 0.01). The plasma contents of pro-albumin, transferrin, and IL-2 were obviously higher than those in the C group (the increase rates were 21.19%, 51.11%, 57.54%, respectively, P < 0.01). The plasma DAO activity, L/M ratio, endotoxin content and urine nitrogen excretion in Gln group were evidently lower than those in C group (the decrease rates were 47.26%, 52.18, 22.22% and 27.78%, respectively, P < 0.05 or 0.01). There was no obvious difference in the plasma levels of total protein and albumin, the indices in blood and urine test, or the hepatic and renal functions between the two groups before and after the amino acid supplementation. Mild side effects such as nausea, diarrhea, constipation occurred in both groups, but all of them disappeared spontaneously afterwards (P > 0.05). CONCLUSION: Oral administration of glutamine could be helpful to increase plasma concentration of glutamine and to ameliorate obviously the intestinal mucosal injury, to promote systemic protein synthesis and to inhibit protein catabolism and to upgrade systemic immune function with little side effect in patients with severe injury.

Administration, Oral↗

PubMed1991

Glutamine metabolism by the endotoxin-injured lung.

The alterations in lung glutamine (GLN) metabolism that occurs in the endotoxin-injured lung were studied in rats and subsequently correlated with flux changes that occur in patients with the adult respiratory distress syndrome (ARDS). Measurements in animals were made at various time-points following the administration of endotoxin, while studies in surgical patients were done in a group of healthy controls, in patients with "early" sepsis who had normal chest x-ray films, and in patients with radiographic and physiologic evidence of ARDS. In healthy control rats, net amounts of GLN are released by the lungs into the systemic circulation. This release rate doubled 30 minutes after intravenous endotoxin (1,580 +/- 320 nmol GLN/100 g BW/min vs. 736 +/- 179 in controls, p less than 0.01) but glutamine synthetase activity was unchanged, suggesting an outpouring of cellular glutamine stores. Two hours after endotoxin treatment, this accelerated fractional release of glutamine by the lungs was no longer detected. By the 12-hour time-point, the lungs reversed to an organ of net glutamine balance (234 +/- 248 nmol/100 g BW/min, p less than 0.05 vs. controls and ENDO30 min) despite a more than two-fold increase in glutamine synthetase activity (p less than 0.01). Simultaneously, lung weights were increased by 21% (p less than 0.01) and histologic examination showed an interstitial infiltrate and pulmonary edema. Similar observations were made in humans; patients with "early" sepsis exhibited a marked increase in lung glutamine release, while patients with ARDS demonstrated glutamine balance across the lungs (4,030 +/- 910 nmol GLN/kg BW/min vs. 637 +/- 496 in ARDS, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Metabolism of glutamine and glutamate by rat renal tubules. Study with 15N and gas chromatography-mass spectrometry.

Gas chromatography-mass spectrometry was utilized to study the metabolism of [15N]glutamate, [2-15N]glutamine, and [5-15N]glutamine in isolated renal tubules prepared from control and chronically acidotic rats. The main purpose was to determine the nitrogen sources utilized by the kidney in various acid-base states for ammoniagenesis. Incubations were performed in the presence of 2.5 mM 15N-labeled glutamine or glutamate. Experiments with [5-15N]glutamine showed that in control animals approximately 90% of ammonia nitrogen was derived from 5-N of glutamine versus 60% in renal tubules from acidotic rats. Experiments with [2-15N]glutamine or [15N]glutamate indicated that in chronic acidosis approximately 30% of ammonia nitrogen was derived either from 2-N of glutamine or glutamate-N by the activity of glutamate dehydrogenase. Flux through glutamate dehydrogenase was 6-fold higher in chronic acidosis versus control. No 15NH3 could be detected in renal tubules from control rats when [2-15N]glutamine was the substrate. The rates of 15N transfer to other amino acids and to the 6-amino groups of the adenine nucleotides were significantly higher in normal renal tubules versus those from chronically acidotic rats. In tubules from chronically acidotic rats, 15N abundance in 15NH3 and the rate of 15NH3 appearance were significantly higher than that of either the 6-amino group of adenine nucleotides or the 15N-amino acids studied. The data indicate that glutamate dehydrogenase activity rather than glutamate transamination is primarily responsible for augmented ammoniagenesis in chronic acidosis. The contribution of the purine nucleotide cycle to ammonia formation appears to be unimportant in renal tubules from chronically acidotic rats.

Acid-Base Equilibrium↗

PubMed1983

Glutamine metabolism in bone.

Evidence is provided for the utilization of glutamine by calvaria and compact bone of rat. Glutamine was actively transported into calvaria, principally by sodium-dependent mechanisms; its uptake was significantly inhibited by neutral amino acids (alanine, proline, serine, asparagine) and glutamine analogs (L-glutamate-gamma-hydroxamate, albizziin). Glutamine was degraded to ammonia and glutamate by phosphate-dependent glutaminase, a mitochondrial enzyme present in both calvaria and compact bone. The enzyme exhibited an apparent Kmgln of 2.35 mM, a KactPO4 of 25 mM, and a broad pH optimum (7.5-9.5). It was inactivated by incubation of intact calvaria or bone homogenates with the glutamine analogs 6-diazo-5-oxo-L-norleucine (DON) and a 2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Such treatment also severely inhibited (greater than 95%) both ammonia and 14CO2 formation from [U-14C]glutamine. Glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities were measured in bone. Amino-oxyacetate, an aminotransferase inhibitor, inhibited 14CO2 formation from [U-14C]glutamine. The data indicate that glutamine can serve as a precursor of ammonia, glutamate, other amino acids (alanine, aspartate, ornithine, proline) and carbon dioxide in bone and that phosphate-dependent glutaminase, transaminases, and citric acid cycle activity contribute to the observed metabolism.

Amino Acids↗

PubMed1982

The stimulus-secretion coupling of amino acid-induced insulin release. Influence of a nonmetabolized analog of leucine on the metabolism of glutamine in pancreatic islets.

L-Glutamine causes a dose-related enhancement of insulin release evoked, in rat pancreatic islets, by the nonmetabolized analog of leucine, 2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH). The influence of BCH upon the metabolism of L-glutamine was investigated. In the islets exposed to L-glutamine, BCH decreased the deamidation of glutamine, but stimulated the oxidative deamination of glutamate, increased the rate of generation and islet content of 2-ketoglutarate, and augmented the oxidation of L-[U-14C]glutamine. BCH antagonized the sparing action of L-glutamine upon the oxidation of endogenous fatty acids. The stimulation of insulin release by the association of L-glutamine and BCH was commensurate with the estimated increase in O2 consumption and coincided with an increase in the islet NADPH/NADP+ ratio, net uptake of 45Ca, and cyclic AMP concentration. It is concluded that insulin release evoked by these amino acids is causally linked to an increase in catabolic fluxes, the secretagogues acting in the islet cells as a fuel (glutamine) or enzyme activator (BCH).

Adenine Nucleotides↗

PubMed1981

Purification and properties of the glutamine- and N-acetyl-L-glutamate-dependent carbamoyl phosphate synthetase from liver of Squalus acanthias.

The L-glutamine- and N-acetyl-L-glutamate-dependent carbamoyl phosphate synthetase III present in liver of spiny dogfish (Squalus acanthias) has been purified to a high state of purity. The purified enzyme has a Mr congruent to 160,000 and is subject to self-association which is facilitated by the presence of MgATP, L-glutamine, and N-acetyl-L-glutamate. The enzyme exhibits hysteretic properties. The time course of the reaction is characterized by a lag or a burst in activity, depending upon preincubation conditions, which can last up to 30 min. The lag period can be eliminated by preincubating the enzyme at 26 degrees C (but not at 4 degrees C) in the presence of the above three ligands. Mg2+ in excess of that required to complex ATP as MgATP and N-acetyl-L-glutamate are both required for full activity. The requirement of K+ for activity can be replaced by NH4+, but not by Na+. Ammonia can act as a substrate in place of L-glutamine, but the maximal rate is much less than that which can be obtained with L-glutamine. The glutamine-dependent activity is inhibited by ammonia. Apparent Km values under optimal conditions for N-acetyl-L-glutamate, L-glutamine, MgATP, bicarbonate, and ammonia are 0.013 mM, 0.16 mM, 0.35 mM, 1.7 mM, and 2 mM, respectively. The apparent Km for N-acetyl-L-glutamate decreases when the concentration of L-glutamine increases, and vice versa. The apparent Km values for these two ligands are increased when urea is present at normal physiological concentrations (0.4 M), and the activity of the enzyme is significantly affected by changes in urea concentration. Compounds known to act as allosteric effectors on other glutamine-dependent carbamoyl phosphate synthetases had little or no effect on this enzyme. The properties of the enzyme are consistent with the view that the function of this carbamoyl phosphate synthetase III is related to the synthesis of urea which is retained in these species as a mechanism for osmoregulation.

Animals↗

PubMed1980

Characteristics of an amino acid transport system in rat liver for glutamine, asparagine, histidine, and closely related analogs.

In the rat hepatocyte, whether freshly separated or in primary culture, we do not find L-glutamine entry by Systems A and ASC as seen in cells previously studied. Instead the mediated entry of glutamine appears to occur exclusively by a Na+-dependent system ("N") apparently specific to amino acid amides and L-histidine; however, a portion of asparagine uptake occurs by System A. The simplest evidence for the separateness of the added system is the failure of model substrates for System A (e.g. N-methylalanine) to inhibit glutamine uptake significantly, and the failure of glutamine to inhibit the uptake of L-cysteine, model substrate for System ASC, at least in this cell. As is the case for cysteine, glutamine inhibits transport by System A (although not competitively), even though showing no transport by that system. Our finding confirms an earlier inference that glutamine uptake by this cell may follow a route not taken by alanine or serine, and explains the apparently erroneous companion inference that glutamine also shares a route with these two amino acids. Its uptake has now been characterized to show a series of differences from Systems A and ASC. Especially significant in view of the importance of glutamine metabolism are an insensitivity of the new system to stimulation by either insulin or glucagon, and its distinct enhancement (not as large as that for System A) on starvation of the cells with respect to amino acids. Hence, a second system has been found to show adaptive regulation.

Amino Acids↗

PubMed1995

Effects of graded glutamine intake on liver protein metabolism following partial hepatectomy.

OBJECTIVE: To elucidate whether glutamine can influence the rate of regeneration and protein metabolism in regenerating liver. DESIGN: Liver regeneration rate, protein content and synthesis were measured in rats 7 days after a liver resection or sham operation. After the operation, the rats were fed three elementary isonitrogenous diets, one without and two including different levels of glutamine. METHODS: Fifty-six rats were randomly assigned to either sham operation or liver resection. After the operation, they received an isonitrogenous, isocaloric elementary diet with a glutamine content of 0, 2 or 4%. The resected part of the liver was weighed and analysed for DNA and protein content. Seven days later, hepatic protein synthesis was measured by the flooding method using L-[3H]-phenylalanine, and the liver was analysed for DNA, RNA and protein content. RESULTS: The regeneration rate was higher in the group receiving 2% glutamine but not in the group receiving 4% glutamine than in the 0% group. Total protein content was increased in regenerating liver in the 2 and 4% glutamine groups compared with the 0% group. Protein synthesis was higher 7 days after liver resection than in sham-operated rats. In the 2% group there was a tendency towards increased protein synthesis compared with the 0% group. CONCLUSION: A diet with normal glutamine content improved liver regeneration rate, total protein content and protein synthesis in regenerating liver, but an excess of glutamine did not enhance this effect.

Animals↗

PubMed1996

[The metabolic role of glutamine].

Glutamine is a non essential amino acid. Nevertheless it has to be considered a "conditionally essential" amino acid for several metabolic reactions in which it is involved. Glutamine is the most abundant amino acid in human plasma and muscle. Because glutamine is highly unsteady, it was never used for enteral and parenteral nutrition in the past. It appears to be a unique amino acid for rapidly proliferating cells serving as a preferred fuel compared to glucose. It seems to be essential for cellular replication such as a "nitrogen carrier" between the tissues. A deficiency state of glutamine causes morphology and functional changing and negative nitrogen metabolism. The need for glutamine is particularly high when metabolism is increased as in the critically ill (surgical stress, sepsis, inflammatory states, fasten, burns) especially in the tissues with a rapid cell turn-over. In these conditions the body requirements of glutamine appear to exceed the individual's muscle deposits (muscle is the most important place of synthesis and storage), causing an increased synthesis with a high energy waste and loss of muscle mass. Glutamine is essential for bowel mucosa trophism and its deficiency in all the catabolic states allows bacterial translocation. In these cases feeding is not sufficient to restore basal conditions. At present enteral or parenteral glutamine supplementations are of high interest for the feeding of critically ill patients.

Digestive System↗

PubMed1996

Glutamine metabolism of intestine grafts: influence of mucosal injury by prolonged preservation and transplantation.

The demand for glutamine increased only in the preserved intestine in the early postoperative period (3 days after transplantation). Glutamine demand of the preserved grafts returned to control and immediate levels 7 and 14 days after transplantation. Three days after intestinal transplantation, when the intestinal mucosa was actively regenerating, the demand for glutamine was markedly enhanced. The enhanced demand for glutamine was met by increased output of glutamine by the liver and skeletal muscle. Glutamine uptake by the intestinal graft was enhanced by a brief infusion of glutamine. Thus, we believe exogenous glutamine supplementation may be beneficial for the recovery of intestinal grafts with severe mucosal injury.

Animals↗

PubMed1999

Glutamine synthesis is heterogeneous and differentially regulated along the rabbit renal proximal tubule.

Glutamine synthesis, a major process for ammonia detoxification and the control of acid-base balance, occurs from various precursors in suspensions of rabbit proximal tubules. However, no data are currently available on the distribution of glutamine synthesis along the rabbit proximal tubule, and its modulation by changes of substrate concentration. Therefore we have microdissected and incubated the three parts (S1, S2 and S3) of rabbit proximal tubules and measured glutamine synthesis from alanine and aspartate. With a physiological concentration of alanine (0.25 mM) or aspartate (0.05 mM), glutamine synthesis in the S1 segment was about half of that in the S2 and S3 segments, and was greater from alanine than from aspartate along the entire proximal tubule. Elevation of alanine and aspartate concentrations to 5 mM increased glutamine synthesis in both a substrate- and segment-dependent manner. It is concluded that glutamine synthesis occurs from alanine and aspartate along the entire rabbit proximal tubule; however, contrary to what might have been expected on the basis of measurement of glutamine synthetase activity, the basal rate of glutamine synthesis and its adaptation to increased substrate availability are heterogeneous along this nephron segment.

Alanine↗

PubMed1996

Cloning and expression of a rat kidney cytosolic glutamine transaminase K that has strong sequence homology to kynurenine pyruvate aminotransferase.

An alpha-keto acid-dependent cysteine S-conjugate beta-lyase of rat kidney was identified as cytosolic glutamine transaminase K by Stevens et al. (J. Biol. Chem. 261, 15529-15537, 1986). Subsequently, a rat kidney protein with both glutamine transaminase K- and cysteine S-conjugate beta-lyase activities was cloned and sequenced by Perry et al. (Mol. Pharmacol. 43, 660-665, 1993). This protein was later shown to be identical with kynurenine pyruvate aminotransferase (Mosca et al., FEBS Lett. 353, 21-24, 1994). Thus, kynurenine pyruvate aminotransferase possesses both glutamine transaminase K- and cysteine S-conjugate beta-lyase-type activities. We have also cloned a cytosolic glutamine transaminase K from a rat kidney cDNA library and expressed the full-length clone in COS1 cells. The transfected cells exhibit marked increases in activities of both glutamine transaminase K and cysteine S-conjugate beta-lyase. The enzyme cloned in the present work is a homodimer. Each subunit has a molecular mass of 45.8 kDa and contains 426 amino acid residues. The sequence of cytosolic glutamine transaminase K obtained in the present work has strong similarities to other aminotransferases, including >90% identity with kynurenine pyruvate aminotransferase. Our preparation of purified rat kidney cytosolic glutamine transaminase K possesses some kynurenine pyruvate aminotransferase activity. Thus, rat kidney cytosol possesses at least two distinct enzymes that catalyze glutamine transaminase K/cysteine S-conjugate beta-lyase/kynurenine pyruvate aminotransferase reactions. The present work underscores the difficulties associated with characterizing aminotransferases with overlapping specificities.

Amino Acid Sequence↗