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Query: CAS:6893-26-1 (glutamate)
 73,096 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Earlier studies have revealed, upon hypophysectomy, a specific increase in mitochondrial urea cycle enzymes, namely carbamyl phosphate synthetase and ornithine transcarbamylase. Administration of growth hormone to hypophysectomized rats brought these enzyme activities back to normal. Since growth hormone plays a role in the formation of citrulline and ultimately urea, in the present study its effect on the levels of N-acetyl-L-glutamate, an allosteric activator of carbamyl phosphate synthetase has been investigated. A significant increase in N-acetyl-L-glutamate concentration in rat liver on hypophysectomy and its reversal back to normal levels on growth hormone administration was reported. These results suggest that the lack of growth hormone tends to amplify urea production by the liver.
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PMID:Effect of growth hormone on rat liver N-acetyl-L-glutamate. 397 20

Chronic administration of technical-grade hexachlorocyclohexane in Swiss male mice resulted in necrosis, and later in adenomatous nodules and hepatocellular carcinomas at 3, 7, and 10 months, respectively, after initiation of the experiment. A definite pattern of changes were observed of arginase, ornithine transaminase, ornithine carbamoyltransferase activities, and metabolites related to ornithine. Conversion of glutamate to ornithine correlated well with the decreased glutamate and constant ornithine in liver of mice fed hexachlorocyclohexane for 7 months.
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PMID:Deviations in ornithine-related metabolism during hexachlorocyclohexane-induced hepatocarcinogenesis in mice: evidence for conversion of glutamate to ornithine. 620 19

Valproate (0.5-5 mM) strongly inhibited urea synthesis in isolated rat hepatocytes incubated with 10 mM-alanine and 3 mM-ornithine. Valproate at the same concentrations markedly decreased concentrations of N-acetylglutamate, an essential activator of carbamoyl-phosphate synthetase I (EC 6.3.4.16), in parallel with the inhibition of urea synthesis by valproate. This compound also lowered the cellular concentration of acetyl-CoA, a substrate of N-acetylglutamate synthase (EC 2.3.1.1); glutamate, aspartate and citrulline were similarly decreased. Valproate in a dose up to 2 mM did not significantly affect the cellular concentration of ATP and had no direct effect on N-acetylglutamate synthesis, carbamoyl-phosphate synthetase I and ornithine transcarbamoylase (EC 2.1.3.3) activities.
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PMID:Inhibition of ureagenesis by valproate in rat hepatocytes. Role of N-acetylglutamate and acetyl-CoA. 641 45

Arginine biosynthesis and its regulation by the presence of different carbon and nitrogen sources in the growth medium of Mycobacterium smegmatis was studied. Replacement of glycerol by glucose and fructose increased the activities of acetylglutamate kinase, acetylornithinase and ornithine transcarbamylase and the enzyme activities of the arginine biosynthetic pathway. The presence of succinate, fumarate, pyruvate or acetate in the growth medium (replacement for citrate) also increased these enzyme activities. However, when glutamate or glutamine was used as nitrogen source in place of asparagine, the enzyme activities decreased. The presence of ornithine or arginine in the growth medium repressed these enzyme activities, though the degree of repression was slight. The phenomenon of repression by arginine and ornithine was confirmed by dialysis experiments. Arginine inhibited the ornithine transcarbamylase activity from cells grown with asparagine as nitrogen source, but activated it when the cells were grown with arginine. Thus, in addition to the weak transcriptional control of arginine biosynthetic enzymes, feedback regulation of ornithine transcarbamylase by arginine also regulated arginine biosynthesis in M. smegmatis grown with asparagine as nitrogen source.
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PMID:Influence of carbon and nitrogen sources on arginine biosynthesis in Mycobacterium smegmatis ATCC 14468. 650 73

Ammonia metabolism was studied in an 8-year-old girl with ornithine transcarbamylase (OTC) deficiency, using 15N-tracer. Changes in the incorporation of 15N into amino acids and urea were examined after 15NH4Cl administration. The recovery of total 15N in the urine of the patient in 3 days was 28.5% of the administered 15N whereas that of a control was 69.3%. They were mostly urea. The recovery of 15N-urea in the patient was 28.8% of the control in 1 day, 32% in 2 days and 33.3% in 3 days after the administration of 15NH4Cl. A larger amount of 15N was incorporated into glutamine (alpha-amino N) and glutamate and 15N was incorporated more rapidly into alanine, asparagine and serine in the patient than in the control. The incorporation into ornithine was less in the patient than in the control.
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PMID:Study of ammonia metabolism in a patient with ornithine transcarbamylase deficiency using an 15N tracer. 661 81

Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.
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PMID:A study of oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following living Escherichia coli injection. 675 40

After prolonged application of ethanol the liver and brain of rats show an appreciable increase in lactate dehydrogenase activity, noticeable lowering of cytoplasmic aspartate and alanine aminotransferase activity, elevation of liver arginine succinate lyase activity with unchanged activities of other enzymes of the ornithine cycle (ornithine carbamoyltransferase and arginase), reduction of glutamate and malate dehydrogenase and mitochondrial aspartate aminotransferase activity in brain tissue. Concurrent application of ethanol and pyridoxine normalizes the effect of ethanol on liver arginine succinate lyase and on brain tissue lactate and malate dehydrogenase, mitochondrial and cytoplasmic aspartate aminotransferase and alanine aminotransferase.
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PMID:[Enzyme activity changes in chronic alcoholic intoxication and the simultaneous administration of pyridoxine]. 689 33

N-Acetylglutamate synthase [EC 2.3.1], which catalyzes the synthesis of N-acetylglutamate, a key effector of carbamoyl-phosphate synthase (ammonia) [EC 6.3.4.16] in the liver of ureotelic animals, was demonstrated to be present in rat small intestinal mucosa. The activity of the enzyme was estimated to be 0.17 nmol N-acetylglutamate formed X (g mucosa)-1 X min-1 at 25 degrees C. Little activity was found in the muscle layer and serosa of the small intestine. The intestinal villous cells were separated from everted intestine, disrupted by nitrogen cavitation, and fractionated into nuclear, mitochondrial, microsomal, and soluble fractions. The mitochondria isolated by this method retained integrity of respiratory function. The mitochondrial fraction was further subjected to isopycnic centrifugation using Percoll (colloidal silica coated with polyvinylpyrrolidone). The activities of N-acetylglutamate synthase and the first two urea cycle enzymes, carbamoylphosphate synthase (ammonia) and ornithine carbamoyltransferase [EC 2.1.3.3], were cofractionated with mitochondrial marker enzymes during the cell fractionation and the isopycnic centrifugation. N-Acetylglutamate synthase, purified 8-fold from the acetone powder extract of small intestinal mucosa, had a high substrate specificity for L-glutamate and acetyl-CoA. The synthase reaction fitted normal Michaelis-Menten kinetics with respect to both L-glutamate (apparent Km, 2.5 mM) and acetyl-CoA (apparent Km, 0.8 mM). L-Arginine stimulated the enzyme activity by increasing the maximal velocity with no effect on apparent Km values for the substrates. These properties were similar to those of the rat liver enzyme (Shigesada & Tatibana (1978) Eur. J. Biochem. 84, 285-291). These results suggest that a function of the intestinal N-acetylglutamate is to activate carbamoyl-phosphate synthase (ammonia) and to allow citrulline synthesis in the tissue.
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PMID:Subcellular localization and properties of N-acetylglutamate synthase in rat small intestinal mucosa. 728 52

Propionic and methylmalonic acidemia are both known to be associated with hyperammonemia. Rats injected with 10 or 20 mmol/kg of propionate or 20 mmol/kg of methylmalonate, along with 1.5 g/kg of a mixture of amino acids, developed severe hyperammonemia, whereas rats administered the same dosages of acetate did not. In vitro, neither propionyl nor methylmalonyl CoA affected the activity of carbamyl phosphate synthetase I, ornithine transcarbamylase, nor the activation constant (K(A)) of carbamyl phosphate synthetase I for N-acetyl glutamate. Furthermore, rats injected with propionate showed no alteration of liver amino acid concentrations, which could explain impaired ureagenesis. Animals injected with methylmalonate showed an increase in both citrulline and aspartate, suggesting that argininosuccinic acid synthetase may also have been inhibited. Liver ATP levels were unchanged. Citrullinogenesis, measured in intact mitochondria from livers of injected animals, was reduced 20-25% by 20 mmol/kg of propionate or methylmalonate (compared with acetate). This effect was attributable to an impairment in the normal rise of liver N-acetyl glutamate content after amino acid injection. Thus, carbamyl phosphate synthetase I activation was reduced. Liver levels of acetyl CoA and free CoA were reduced. Levels of unidentified acyl CoA derivatives rose, presumably reflecting the accumulation of propionyl and methylmalonyl CoA. Thus, the principal mechanism for hyperammonemia induced by these acids is depletion of liver N-acetyl glutamate, which is in turn attributable to depletion of acetyl CoA and/or competitive inhibition by propionyl and methylmalonyl CoA of N-acetyl glutamate synthetase. Injection of methylmalonate may also have an additional inhibitory effect on argininosuccinic acid synthetase.
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PMID:Failure of the normal ureagenic response to amino acids in organic acid-loaded rats. Proposed mechanism for the hyperammonemia of propionic and methylmalonic acidemia. 740 Mar 25

This study was designed to determine whether pyrroline-5-carboxylate (P-5-C) synthase is deficient in chick enterocytes therefore resulting in the lack of synthesis of ornithine and citrulline from glutamine. Post-weaning pig enterocytes, which are known to contain P-5-C synthase and to synthesize both ornithine and citrulline from glutamine, were used as positive controls. Enterocytes were incubated at 37 degrees C for 0-30 min in the presence of 2 mM [U-14C]glutamine or 2 mM ornithine plus 2 mM NH4Cl. In chick enterocytes, glutamine was metabolized to NH3, CO2, glutamate, alanine and aspartate, but not to ornithine, citrulline, arginine or proline. Likewise, there was no formation of citrulline, arginine, alanine or aspartate from ornithine in chick enterocytes. Furthermore, the rate of conversion of ornithine into proline in chick enterocytes was only about 4% of that in cells from pigs. To elucidate the reason for the inability of chick enterocytes to synthesize ornithine and citrulline from glutamine, the activities of the enzymes involved were measured. No activity of P-5-C synthase or ornithine carbamoyltransferase was found in chick enterocytes, in contrast with cells from post-weaning pigs. It was also demonstrated that the activity of ornithine aminotransferase in chick enterocytes was only 3% of that in cells from pigs. Thus the present findings elucidate the biochemical reason for the lack of endogenous synthesis of ornithine and citrulline in chicks. Our results also explain previous observations that ornithine cannot replace arginine or proline in the diet of chicks. We suggest that the absence of P-5-C synthase and ornithine carbamoyltransferase in enterocytes is the metabolic basis for the nutritional requirement of arginine in the chick.
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PMID:Glutamine metabolism in chick enterocytes: absence of pyrroline-5-carboxylase synthase and citrulline synthesis. 770 65


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