Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ammonia, lactate and glutamate levels and the activities of glutamine synthetase (GS), glutamate dehydrogenase (GDH), glutaminase (GLN), aspartate transaminase (AST), phosphofructokinase (PFK) and monoamine oxidase (MAO) were compared in the brain tissue of normal and P. yoelii infected mice. The brain lactate increased by 96% at peak parasitaemia. Cerebral ammonia also exhibited an increase in infected mice which was parasitaemia dependent, while glutamate remained almost unchanged. The brain glutamine synthetase registered an increase of 35% (P < 0.001) in post-mitochondrial fractions, this effect being perceptible even at low parasitaemia, but attained constancy at parasitaemia levels higher than 20%. The activity of monoamine oxidase and phosphofructokinase increased by 105% (P < 0.02) and 41% (P < 0.05) respectively while glutamate dehydrogenase decreased by 15% (P < 0.001). Glutaminase and aspartate transaminase were not significantly influenced by infection (tested only at high parasitaemia levels). It has been postulated that cerebral hypoxia and aberrations in ammonia metabolism may both contribute towards malaria induced cerebral complications.
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PMID:Cerebral ammonia levels and enzyme changes during Plasmodium yoelii infection in mice. 136 Oct 9

The intra-cochlear distributions of aspartate aminotransferase and glutaminase, prominent enzymes of aspartate and glutamate metabolism, have been studied by quantitative microchemical techniques. Also measured was choline acetyltransferase, the enzyme synthesizing acetylcholine, and a marker for the olivocochlear bundle. Aspartate aminotransferase activity was highest in the stria vascularis, about half this high in the organ of Corti synaptic (hair cell) zones, somewhat lower in the organ of Corti non-synaptic (Hensen's cell) zones, lower yet in Reissner's and lowest in the tectorial membrane. Glutaminase, on the other hand, had its highest activity in synaptic zones, about a third of that activity in the organ of Corti non-synaptic zones, and a barely detectable activity in Reissner's and tectorial membranes, and stria vascularis. Seven days after transection of the olivocochlear bundle, no significant difference was found between lesion- and control-side aspartate aminotransferase or glutaminase activities, even though no choline acetyltransferase activity remained in the lesion-side of the organ of Corti. Both the distribution of aspartate aminotransferase activity and the lesion results would seem to implicate it in energy more so than neurotransmitter metabolism. The distribution of glutaminase activity could be consistent with a role in neurotransmission; however, the lesion data were unable to demonstrate a specific association with the olivocochlear bundle.
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PMID:Quantitative distributions of aspartate aminotransferase and glutaminase activities in the rat cochlea. 302

The distributions of glutaminase and aspartate aminotransferase were studied immunocytochemically in the cerebellum of the guinea pig and the rat. In the granule cell layer, both antibodies gave a similar staining pattern. Granule cell bodies were labeled, but staining was also found to lie outside the cell body, associated with what appear to be synaptic processes. In the molecular and Purkinje cell layers, aspartate aminotransferase was concentrated in stellate and basket cell bodies and in terminal baskets beneath Purkinje cells. Glutaminase, however, was not concentrated in these structures.
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PMID:Immunocytochemical localization of aspartate aminotransferase and glutaminase immunoreactivities in the cerebellum. 351 Jun 91

There is considerable evidence that pathways of the hippocampus use an excitatory amino acid as transmitter. We have attempted to immunocytochemically identify excitatory amino acid neurons in the hippocampus of the rat and guinea pig using antiserum to glutaminase and antiserum to aspartate aminotransferase, which have been proposed as markers for aspartergic/glutamergic neurons. Glutaminase-like immunoreactivity was seen in granule cells in the dentate gyrus and fibers and puncta associated with the mossy fiber pathway in the hilus and stratum lucidum of the hippocampus. At the ultrastructural level, glutaminase-like immunoreactivity was observed in mossy fiber terminals in the stratum lucidum. Glutaminase-like immunoreactivity was also seen in pyramidal cells in regio inferior and regio superior and in cells in layer two of the entorhinal cortex. Schaffer collateral terminals, commissural fiber terminals and perforant pathway terminals were not seen at the light microscopic level. Glutaminase-like immunoreactivity is thus found in the cell bodies of proposed excitatory amino acid neurons of hippocampal pathways, but does not appear to label all terminals. Aspartate aminotransferase-like immunoreactivity was not seen in any cells, fibers or terminals in the rat or guinea pig hippocampus.
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PMID:Immunocytochemical localization of glutaminase-like and aspartate aminotransferase-like immunoreactivities in the rat and guinea pig hippocampus. 388 76

Distribution of activity of phosphate-activated glutaminase, aspartate aminotransferase (AST), choline acetyltransferase (CAT) and gamma-aminobutyric acid transaminase (gamma-Abu T) in brain hippocampal formation was studied in 6 people aged 23-65 years using histochemical methods. AST marks axonic systems in neuropil layers of Ammon's horn. Glutaminase is localised in perikarya and proximal segments of pyramidal and granular neurons dendrites. CAT is identified in terminal-like dotted structures in pyramidal and granular layers and also in certain nonpyramidal cells of stratum lacunosum molecular of field CAI. Product of histochemical reaction to gamma-Abu-T stains pericellular plexuses in basis layers of Ammon's horn and denticulate fascia. A generalizing scheme of neurochemical organization of hippocampal formation links is represented in the study.
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PMID:[The neurochemical characteristics of the neurons in the human hippocampal formation]. 916 12

100 mg of taurine per kg body weight had been administered intraperitoneally and 30 min after the administration the animals were sacrificed. Glutamate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, glutaminase, glutamine synthetase, glutamate decarboxylase and GABA aminotransferase along with the content of glutamate and GABA in cerebral cortex, cerebellum and brain stem were studied and compared with the same obtained in the rats treated with normal saline in place of taurine. The results indicated a significant decrease in the activity of glutamate dehydrogenase in cerebral cortex and cerebellum and a significant increase in brain stem. Glutaminase and glutamine synthetase were found to increase significantly both in cerebral cortex and cerebellum. The activities of glutamate decarboxylase was found to increase in all the three regions along with a significant decrease in GABA aminotransferase while the content of glutamate showed a decrease in all the three brain regions, the content of GABA was observed to increase significantly. The above effects of taurine on the metabolism of glutamate and GABA are discussed in relation to the functional role of GABA and glutamate. The results indicate that taurine administration would result in a state of inhibition in brain.
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PMID:Acute metabolic effects of taurine on the enzymes metabolizing glutamate and gaba. 2049 55

Optimization of bioprocesses with mammalian cells mainly concentrates on cell engineering, cell screening and medium optimization to achieve enhanced cell growth and productivity. For improving cell lines by cell engineering techniques, in-depth understandings of the regulation of metabolism and product formation as well as the resulting demand for the different medium components are needed. In this work, the relationship of cell specific growth and uptake rates and of changes in maximum in vitro enzyme activities with intracellular metabolite pools of glycolysis, pentose phosphate pathway, citric acid cycle and energy metabolism were determined for batch cultivations with AGE1.HN.AAT cells. Results obtained by modeling cell growth and consumption of main substrates showed that the dynamics of intracellular metabolite pools is primarily linked to the dynamics of specific glucose and glutamine uptake rates. By analyzing maximum in vitro enzyme activities we found low activities of pyruvate dehydrogenase and pyruvate carboxylase which suggest a reduced metabolite transfer into the citric acid cycle resulting in lactate release (Warburg effect). Moreover, an increase in the volumetric lactate production rate during the transition from exponential to stationary growth together with a transient accumulation of fructose 1,6-bisphosphate, fructose 1-phosphate and ribose 5-phosphate point toward an upregulation of PK via FBP. Glutaminase activity was about 44-fold lower than activity of glutamine synthetase. This seemed to be sufficient for the supply of intermediates for biosynthesis but might lead to unnecessary dissipation of ATP. Taken together, our results elucidate regulation of metabolic networks of immortalized mammalian cells by changes of metabolite pools over the time course of batch cultivations. Eventually, it enables the use of cell engineering strategies to improve the availability of building blocks for biomass synthesis by increasing glucose as well as glutamine fluxes. An additional knockdown of the glutamine synthetase might help to prevent unnecessary dissipation of ATP, to yield a cell line with optimized growth characteristics and increased overall productivity.
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PMID:The influence of cell growth and enzyme activity changes on intracellular metabolite dynamics in AGE1.HN.AAT cells. 2465 47

Glutaminase 1 (GLS1) expression is increased in non-small cell lung cancer (NSCLC). GLS1 knockdown using siRNA or inhibition using bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) induced cell cycle arrest with significant reduction of ATP level while levels of reactive oxygen species or glutathione were not affected in NSCLC cell lines. Recently we found that NSCLC significantly depends on cytosol NADH for ATP production. GLS1 remarkably contributes to ATP production through transferring cytosolic NADH into mitochondria via malate-aspartate shuttle by supply of glutamate in NSCLC. Regulation of malate-aspartate shuttle by knockdown or inhibition of glutamic-oxaloacetic transaminase 2 or malate dehydrogenase 2 mimicked GLS1 knockdown, which induced cell death with ATP reduction in NSCLC. Therefore, GLS1 inhibition induced cell cycle arrest with ATP depletion by glutamate reduction. Dual inhibition with BPTES and thymidylate synthase inhibitor, 5-fluorouracil (5-FU), elicits cell death synergistically through cell cycle arrest in NSCLC. A preclinical xenograft model of NSCLC showed remarkable anti-tumour effect synergistically in the BPTES and 5-FU dual therapy group.
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PMID:Dual targeting of glutaminase 1 and thymidylate synthase elicits death synergistically in NSCLC. 2792 35