Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine is actively metabolized in human platelets, representing a preferential mitochondrial oxidative substrate in these cells. The primary importance of this metabolic route of glutamine is further confirmed here by the observation that platelet glutaminase activity is entirely represented by the phosphate dependent glutaminase or glutaminase I, most probably localized in the mitochondrial platelet fraction and classified by kinetic analysis as a kidney-type form. The following step of the glutamine metabolizing pathway, allowing the entrance of the amino acid skeleton carbons in the Krebs cycle, might be catalyzed by both glutamate dehydrogenase and aspartate transaminase, the first being entirely mitochondrial and the latter 65% mitochondrial. We also investigated platelets for the presence of one or more specific transport systems involved in glutamine uptake and we present the first evidence for two glutamine transport systems in human platelets that by inhibition analysis appear to share characteristics with the Na(+)-dependent ASC system and the Na(+)-independent L system for dipolar amino acid uptake. Both systems display affinity characteristics for glutamine in the range of plasma glutamine concentration and may thus have physiological relevance for the uptake of the amino acid in these cells.
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PMID:Glutamine transport and enzymatic activities involved in glutaminolysis in human platelets. 782 6

L-Glutamate is the immediate precursor of the inhibitory transmitter GABA, and considered to be supplied from alpha-ketoglutarate through a transamination reaction or from glutamine through a glutaminase reaction. In the present study, the localization of aspartate aminotransferase and glutaminase in GABAergic neurons was investigated in the rat neocortex by a double immunofluorescence method. Immunoreactivities for both soluble and mitochondrial aspartate aminotransferases were detected in more than 90% of GABA-positive neurons, whereas glutaminase immunoreactivity was not found in GABA-positive neurons. All neocortical neurons with soluble aspartate aminotransferase immunoreactivity were immunopositive for GABA, but none for glutaminase. Neurons with mitochondrial aspartate aminotransferase immunoreactivity showed either glutaminase or GABA immunoreactivity. Under confocal laser scan microscopy, immunoreactivity for soluble aspartate aminotransferase was observed in many axons and axon terminals showing immunoreactivity for glutamic acid decarboxylase, whereas immunoreactivity for mitochondrial aspartate aminotransferase was seen in only a few axons displaying immunoreactivity for glutamic acid decarboxylase. The present results indicate that soluble aspartate aminotransferase is selectively localized to cell bodies and axon terminals of GABAergic non-pyramidal neurons in the cerebral neocortex. This suggests that glutamate is supplied from alpha-ketoglutarate via transamination and works as the immediate precursor for GABA in axon terminals of GABAergic neurons. The absence of glutaminase immunoreactivity in GABAergic neurons indicates that glutamine is a "metabolically remote" precursor for GABA. Mitochondrial aspartate aminotransferase was located in perikarya, rather than in axon terminals of GABAergic neurons, suggesting a transmitter-irrelevant role of this enzyme in neurons.
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PMID:Glutamate-synthesizing enzymes in GABAergic neurons of the neocortex: a double immunofluorescence study in the rat. 783 83

The quantitative distributions of aspartate aminotransferase and glutaminase were mapped in subregions of olfactory bulb and cochlear nucleus of rat, and were compared with similar data for retina and with the distributions of their substrate and product amino acids aspartate, glutamate, and glutamine. The distributions of both enzymes paralleled that of aspartate in the olfactory bulb and that of glutamate in the cochlear nucleus. In retina (excluding inner segments), there were similarities between aspartate aminotransferase and both glutamate and aspartate distributions. The distribution of gamma-aminobutyrate (GABA) was similar to those of both enzymes in olfactory bulb, to aspartate aminotransferase in cochlear nucleus, and to glutaminase in retina (excluding inner segments). The results are consistent with significant involvement of aspartate aminotransferase, especially the cytosolic isoenzyme, and glutaminase in accumulation of the neurotransmitter amino acids glutamate, aspartate, and GABA, although with preferential accumulation of different amino acids in different brain regions.
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PMID:Aspartate aminotransferase and glutaminase activities in rat olfactory bulb and cochlear nucleus; comparisons with retina and with concentrations of substrate and product amino acids. 791 16

Pathophysiological concentrations of ammonia, both in vivo and in vitro, suppressed the oxidation of glutamate by rat cerebellar mitochondria. The transport of glutamate into mitochondria was either unaltered or enhanced during hyperammonemic states. Activities of mitochondrial enzymes, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, glutaminase, and GABA-transaminase were suppressed during hyperammonemic states. Suppression of 14CO2 production with (aminooxy)acetic acid but not with glutamic acid diethyl ester indicated that transamination but not oxidative deamination of glutamate plays a major role in glutamate oxidation during normal and hyperammonemic states.
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PMID:Transport and metabolism of glutamate by rat cerebellar mitochondria during ammonia toxicity. 810 3

Gabapentin is a novel anticonvulsant drug. The anticonvulsant mechanism of gabapentin is not known. Based on the amino acid structure of gabapentin we explored its possible effects on glutamate and gamma-aminobutyric acid (GABA) metabolism in brain as they may relate to its anticonvulsant mechanisms of action. Gabapentin was tested for its effects on seven enzymes in the metabolic pathways of these two neurotransmitters: alanine aminotransferase (AL-T), aspartate aminotransferase (AS-T), GABA aminotransferase (GABA-T), branched-chain amino acid aminotransferase (BCAA-T), glutamine synthetase (Gln-S), glutaminase (GLNase), and glutamate dehydrogenase (GDH). In the presence of 10 mM gabapentin, only GABA-T, BCAA-T, and GDH activities were affected by this drug. Inhibition of GABA-T by gabapentin was weak (33%). The Ki values for inhibition of cytosolic and mitochondrial forms of GABA-T (17-20 mM) were much higher than the Km values for GABA (1.5-1.9 mM). It is, therefore, unlikely that inhibition of GABA-T by gabapentin is clinically relevant. As with leucine, gabapentin stimulated GDH activity. The GDH activity in rat brain synaptosomes was activated 6-fold and 3.4-fold, respectively, at saturating concentrations (10 mM) of leucine and gabapentin. The half-maximal stimulation by gabapentin was observed at approximately 1.5 mM. Gabapentin is not a substrate of BCAA-T, but it exhibited a potent competitive inhibition of both cytosolic and mitochondrial forms of brain BCAA-T. Inhibition of BCAA-T by this drug was reversible. The Ki values (0.8-1.4 mM) for inhibition of transamination by gabapentin were close to the apparent Km values for the branched-chain amino acids (BCAA) L-leucine, L-isoleucine, and L-valine (0.6-1.2 mM), suggesting that gabapentin may significantly reduce synthesis of glutamate from BCAA in brain by acting on BCAA-T.
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PMID:Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. 856 62

Homogenates of specific brain regions of three sensory systems (auditory, olfactory, and visual) were prepared from pigmented Long-Evans Hooded rats and assayed for amino acid concentrations and activities of glutaminase, aspartate aminotransferase (total, cytosolic, and by difference, mitochondrial), malate dehydrogenase, lactate dehydrogenase, and choline acetyltransferase. Comparing the quantitative distributions among regions revealed significant correlations between AAT and aspartate, between glutaminase and glutamate, between glutamate and glutamine, and between AAT plus glutaminase, or glutaminase alone, and the sum of aspartate, glutamate, and GABA, suggesting a metabolic pathway involving the synthesis of a glutamate pool as precursor to aspartate and GABA. Of the inhibitory transmitter amino acids, GABA concentrations routinely exceeded those of glycine, but glycine concentrations were relatively high in brainstem auditory structures.
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PMID:Amino acid concentrations and selected enzyme activities in rat auditory, olfactory, and visual systems. 878 12

Freshwater fish, Cyprinus carpio, was exposed to sublethal concentration (3 microg liter-1) of cypermethrin for 5 and 10 days to examine the changes in the transamination process during the formation of nitrogenous end products in four functionally different tissues, namely, gill, liver, brain, and muscle. Increases in total and soluble protein contents were noticed in all the tissues of exposed fish with a decrease in free amino acids and protease activity. Activity levels of both the transaminases, aspartate aminotransferase and alanine aminotransferase, and glutamate dehydrogenase were elevated, indicating active transamination and oxidative deamination. Attenuation of ammonia was consistent in both treatment groups. However, urea level decreased at the 5-day exposure period but increased by Day 10, manifesting the conversion of toxic ammonia to urea. Glutamine content was consistently raised upon exposure to the toxicant. In support of this, increases in glutamine synthetase and suppression of glutaminase were noticed. It clearly indicates that ammonia is not stored in the tissues in spite of active oxidative deamination when the fish is in a polluted environment. All the observations made demonstrate that the fish has adopted more than one compensatory mechanism during the process of transamination of nitrogenous products.
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PMID:Action of cypermethrin on tissue transamination during nitrogen metabolism in Cyprinus carpio. 881 84

We present the setup of a flow injection analysis system designed for on-line monitoring of glutamate and glutamine. These amino acids represent a major energy source in mammalian cell culture. A cycling assay consisting of glutamate dehydrogenase and aspartate aminotransferase produces NADH proportional to the glutamate concentration in the sample. NADH is then measured spectrophotometrically. Glutamine is determined by conversion to glutamate which is fed into the cycling assay. The conversion of glutamine to glutamate is catalyzed by asparaginase. Asparaginase was used in place of glutaminase due to its relatively high reactivity with glutamine and a pH optimum similar to that of glutamate dehydrogenase. The enzymes were immobilized covalently to activated controlled pore glass beads and integrated into the flow injection analysis system. The application of the immobilized enzymes and the technical setup are presented in this paper.
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PMID:Enzyme-based flow injection analysis system for glutamine and glutamate in mammalian cell culture media. 1003 69

Chronic treatment of rats from postnatal day 6 to 25 with drugs that interact with the N-methyl-D-aspartate (NMDA) receptor induced a differential effect on the activity of some enzymes involved in neurotransmitter synthesis. Two of these drugs ((5R,10S)-(+)-5-methyl-10,11 -dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine hydrogen maleate (MK-801) and 3-(2-carboxypiperazin-4-yl)propyl-1phosphonic acid (CPP)) caused a marked reduction (20-40%) of glutaminase and aspartate aminotransferase activity in the cerebellum. These changes were observed only at a very precise time of development (i.e. 10 to 19 postnatal day). The competitive antagonist, amino phosphonovaleric acid (APV), did not affect any of the enzymes studied at all tested ages. When animals were treated with NMDA only a slight, but significant, increase in the activity of glutaminase was observed at 9-11 postnatal day only. Any of the agonists or antagonists tested significantly affected the activity of lactate dehydrogenase as compared to control animals. Histologic observations of cerebella treated with the indicated drugs showed that only MK-801, and CPP to a lesser extent, induced a small reduction in the width of the internal granule layer. The body weight of animals treated with MK-801 was clearly reduced, but only in more mature rats (> 16 postnatal day), when animals did not show any alteration in the enzymes tested. These results support the suggestion that presynaptic influences, particularly from glutamatergic neurons, are critical to promote cerebellar granule neurons differentiation during critical periods of the cerebellar development.
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PMID:Effect of NMDA antagonists on the activity of glutaminase and aspartate aminotransferase in the developing rat cerebellum. 1021 61

Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria.
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PMID:Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas. 1039 49


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