Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of [15N]glutamate was studied with gas chromatography-mass spectrometry in rat brain synaptosomes incubated with and without glucose. [15N]Glutamate was taken up rapidly by the preparation, reaching a steady-state level in less than 5 min. 15N was incorporated predominantly into aspartate and, to a much lesser extent, into gamma-aminobutyrate. The amount of [15N]ammonia formed was very small, and the enrichment of 15N in alanine and glutamine was below the level of detection. Omission of glucose substantially increased the rate and amount of [15N]aspartate generated. It is proposed that in synaptosomes (a) the predominant route of glutamate nitrogen disposal is through the aspartate aminotransferase reaction; (b) the aspartate aminotransferase pathway generates 2-oxoglutarate, which then serves as the metabolic fuel needed to produce ATP; (c) utilization of glutamate via transamination to aspartate is greatly accelerated when flux through the tricarboxylic acid cycle is diminished by the omission of glucose; (d) the metabolism of glutamate via glutamate dehydrogenase in intact synaptosomes is slow, most likely reflecting restriction of enzyme activity by some unknown factor(s), which suggests that the glutamate dehydrogenase reaction may not be near equilibrium in neurons; and (e) the activities of alanine aminotransferase and glutamine synthetase in synaptosomes are very low.
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PMID:Glucose and synaptosomal glutamate metabolism: studies with [15N]glutamate. 290 Aug 79

Of many glutamatergic parameters studied in human Huntington's disease, the following abnormalities were documented in the literature: Decreased glutamate content in cerebrospinal fluid and frontal cortex. Decreased activities of glutamine synthetase, ornithine aminotransferase and aspartate aminotransferase in various brain regions, especially the frontal cortex, caudate nucleus and putamen. Decreased glutamate binding in fibroblast membranes. Although it has been hypothesized that Huntington's disease may have a glutamate-related etiology, presently available evidence is too fragmented and inadequate for any conclusion to be made. However, it is noted that interpretation of these human data is very difficult because of two reasons. Firstly, changes observed in postmortem Huntington's disease brains may only be secondary to the disease instead of being the cause of the disease. Secondly, there is always doubts as to the relevance of data obtained with non-neural tissues such as fibroblasts and platelets.
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PMID:Abnormalities in glutamatergic mechanisms in human Huntington's disease. 298 4

The mechanism by which pentylenetetrazole provokes convulsions in animals has been investigated by measuring its influence in vitro on the activities of several enzymes of glutamate metabolism in rat brain homogenates. Pentylenetetrazole does not affect the specific activities of glutamine synthetase, glutaminase, or glutamate decarboxylase; it inhibits those of glutamate dehydrogenase and aspartate aminotransferase, and stimulates that of gamma-aminobutyric acid (GABA) aminotransferase. The overall consequence of the action of pentylenetetrazole on the activities of these enzymes should be an increase in the concentration of glutamate and a decrease in that of GABA. This modulation of glutamate and GABA metabolism by pentylenetetrazole could contribute to the triggering of convulsions.
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PMID:Pentylenetetrazole inhibits glutamate dehydrogenase and aspartate aminotransferase, and stimulates GABA aminotransferase in homogenates from rat cerebral cortex. 321 59

The mechanism of ammonia assimilation in Methanosarcina barkeri and Methanobacterium thermoautotrophicum was documented by analysis of enzyme activities, 13NH3 incorporation studies, and comparison of growth and enzyme activity levels in continuous culture. Glutamate accounted for 65 and 52% of the total amino acids in the soluble pools of M. barkeri and M. thermoautotrophicum. Both organisms contained significant activities of glutamine synthetase, glutamate synthase, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase. Hydrogen-reduced deazaflavin-factor 420 or flavin mononucleotide but not NAD, NADP, or ferredoxin was used as the electron donor for glutamate synthase in M. barkeri. Glutamate dehydrogenase activity was not detected in either organism, but alanine dehydrogenase activity was present in M. thermoautotrophicum. The in vivo activity of the glutamine synthetase was verified in M. thermoautotrophicum by analysis of 13NH3 incorporation into glutamine, glutamate, and alanine. Alanine dehydrogenase and glutamine synthetase activity varied in response to [NH4+] when M. thermoautotrophicum was cultured in a chemostat with cysteine as the sulfur source. Alanine dehydrogenase activity and growth yield (grams of cells/mole of methane) were highest when the organism was cultured with excess ammonia, whereas growth yield was lower and glutamine synthetase was maximal when ammonia was limiting.
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PMID:Ammonia assimilation and synthesis of alanine, aspartate, and glutamate in Methanosarcina barkeri and Methanobacterium thermoautotrophicum. 612 78

A two-stage surgical occlusion of the portal vein was employed to produce hyperammonaemia in the rat. The procedure resulted in a significant rise of arterial blood ammonia level from 70 . 5 +/- 6 . 5 mumol/l (mean +/- SEM, n = 10) to 214 . 0 +/- 37 . 7 mumol/l and in a rise of venous blood ammonia from 65 . 0 +/- 9 . 4 mumol/l to 122 . 2 +/- 7 . 4 mumol/l during the first day following the complete vein occlusion. A marked increase of the arteriovenous difference of ammonia concentration from virtually zero in sham-operated controls to 72 +/- 9 (n = 8) mumol/l in rats 1 day after the surgical manipulation suggested uptake of ammonia by skeletal muscle. Rat muscle glutamine synthetase activity increased from 0 . 46 +/- 0 . 06 u/mg (n = 7) in controls to 2 . 7 +/- 0 . 3 u/mg (n = 7) on the fourth day following portal vein ligation, and muscle branched chain amino acids aminotransferase increased from 0 . 2 +/- 0 . 05 u/mg in controls to 0 . 96 +/- 0 . 1 u/mg (n = 7) during the first day of ligation. Glutamine dehydrogenase and aspartate aminotransferase activities were not affected by the surgical procedure. These observations suggest that ammonia trapping in skeletal muscle is coupled to glutamine formation via amination of glutamic acid. This conclusion was further supported by the finding that ammonia uptake correlated (r = 0 . 92) with enhanced release of glutamine from muscle and that treatment with methionine sulfoximine, a potent inhibitor of glutamine synthetase, changed the arteriovenous difference of glutamine from -0 . 92 +/- 0 . 01 mmol/l in ligated animals (net release) to +0 . 12 +/- 0 . 01 mmol/l (net uptake) in ligated and inhibitor-treated animals. Similarly, the inhibitor also abolished the arterio-venous difference of ammonia. Thus, the animal model of hyperammonaemia and the muscle enzyme assays reveal that skeletal muscle is involved in the regulation of blood ammonia level by conversion of ammonia, via glutamic acid, to glutamine.
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PMID:Ammonia uptake by skeletal muscle in the hyperammonaemic rat. 612 77

The enzymes of glutamate metabolism were estimated in astrocytes isolated from brains of normal rats and those injected with the potent convulsant, methionine sulfoximine (MSO), which inhibits glutamine synthetase and induces Alzheimer type II astrocytosis. The wet weight, dry weight; contents of DNA, RNA, protein and the activities of glutamate dehydrogenase and aspartate aminotransferase were elevated following MSO administration. The metabolic effects of MSO were found to be different from those of ammonia wherein a fall in the activity of glutamate dehydrogenase and an increase in the activity of glutamine synthetase was noticed. Based on these results it is suggested that there might be an inverse relationship in the functioning of these two enzymes. Such a relationship would help in preventing the depletion of energy pools in a given cellular compartment during ammonia detoxification.
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PMID:Effects of methionine sulfoximine on the enzymes of glutamate metabolism in isolated astrocytes of rat brain. 614 Sep 23

Enzymes of glutamate metabolism were studied in synaptosomes prepared from normal rats and those treated with acute (300 mg/kg) and subacute (150 mg/kg) doses of the convulsant methionine sulfoximine (MSO). The activities of glutamine synthetase, glutamate dehydrogenase and aspartate aminotransferase were inhibited in the synaptosomes of drug treated animals. It is suggested that MSO would suppress the formation of glutamine and glutamate and consequently the releasable pool of glutamate, aspartate and GABA. These neurotransmitters would be depleted from the nerve endings. It is also indicated that the ammonia accumulated would affect the cerebral functioning by interfering with the maintenance of ionic gradients.
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PMID:Suppression of the enzymes of glutamate metabolism in cortical synaptosomes in methionine sulfoximine toxicity. 614 87

Lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), aspartate aminotransferase (AAT), glutamate dehydrogenase (GDH), AMP deaminase, ornithine transcarbamylase (OTC), arginase and glutamine synthetase (GS) activities were increased in the kidney of the rat during repeated ethanol loading. The significance of these findings is discussed.
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PMID:Renal ammonia metabolic response in the rat to repeated ethanol loading. 648 7

Fractionation of cell organelles of nitrogen-fixing nodules of cowpea (Vigna unguiculata L. Walp) by discontinuous and continuous sucrose density centrifugation indicated that starch-containing plastids possessed the complete pathway for purine nucleotide synthesis together with significant activities of some other enzymes associated with the provision of substrates in purine synthesis; triosephosphate isomerase (EC 5.3.1.1), NADH-glutamate synthase (EC 2.6.1.53), aspartate aminotransferase (EC 2.6.1.1), phosphoglycerate oxidoreductase (EC 1.1.1.95), and methylene tetrahydrofolate oxidoreductase (EC 1.5.1.5). Enzymes of purine oxidation, xanthine oxidoreductase (EC 1.2.3.2), and urate oxidase (EC 1.7.3.3) were recovered in the soluble fraction; glutamine synthetase (EC 6.3.1.2) occurred in bacteroids and in the cytosol. Intact, infected (bacteroid-containing) and uninfected cells were prepared by enzymatic maceration of the central zone of the nodule and partially separated by centrifugation on discontinuous sucrose gradients. Glutamine synthetase was largely restricted to infected cells whereas plastid enzymes, de novo purine synthesis, and urate oxidase were present in both cell types. Although the levels of all enzymes assayed were higher in infected cells, both cell types possessed the necessary enzyme complement for ureide formation. A model for the cellular and subcellular organization of nitrogen metabolism and the transport of nitrogenous solutes in cowpea nodules is proposed.
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PMID:Cellular and subcellular organization of pathways of ammonia assimilation and ureide synthesis in nodules of cowpea (Vigna unguiculata L. Walp.). 687 Feb 68

We measured the levels of three glutamate metabolizing enzymes, namely, glutamate dehydrogenase (GDH), aspartate aminotransferase (AAT), and glutamine synthetase (GS) in cerebellar and occipital cortices of nine patients with dominantly-inherited olivopontocerebellar atrophy (OPCA; spinocerebellar ataxia type I). As compared with the controls, mean GDH activities in cerebellar cortex of the OPCA patients were normal whereas levels of AAT (-17%) and the glial enzyme GS (-27%) were significantly reduced. No statistically significant changes were observed in occipital cortex, a morphologically unaffected brain area. We suggest that the decreased GS levels could reflect impaired capacity of astrocytes to metabolize glutamate which might contribute to the degenerative processes in OPCA cerebellum.
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PMID:Cerebellar glutamate metabolizing enzymes in spinocerebellar ataxia type I. 791 69


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