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)

The administration of L-alpha-amino-beta-chloropropionic acid hydroxamide (L-ACPH) to mice brought about an inhibition in GABA-T activity in the brain of the animals, a significant inhibition occurring with dosage levels as low as 0.25 mmol/kg. Minimum levels of GABA-T activity were reached 3 h after administration of the drug. Brain glutamic acid decarboxylase, DOPA decarboxylase and aspartate aminotransferase activities were not altered by the L-ACPH but alanine aminotransferase activity was totally inhibited. Slight changes in structure caused great changes in the potency of the drugs. For example, the elongation of the L-ACPH structure by one carbon, or a change in the configuration of the amino group from L- to D-, caused a significant decrease in GABA inhibition. The chloro and hydroxamide groups were necessary for inhibitory activity. The administration of L-ACPH to mice delayed the onset of drug induced seizures but had a less noticeable effect against maximal electroshock. The addition of L-ACPH to crude extracts from brain, or to preparations of semipurified GABA-T, also inhibited GABA-T activity. Again the development of the inhibition was time-dependent. Possible mechanisms of action with respect to L-ACPH induced inhibition of GABA-T activity are discussed in the light of the data presented.
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PMID:Alteration of GABA metabolism in mammalian brain by l-alpha-amino-beta-chloropropionic acid hydroxamide and related compounds. 45 23

Chronically alcoholized intoxication (1.5--2 months) induces adaptation of cerebral neurones to changing equilibrium states of biochemical processes by altering the activity of enzymes of GABA metabolism, reduction of alanine and aspartate transaminase activity and increase of LDH and succinate dehydrogenase activity. In the cerebellum and cerebral hemispheres during alcohol abstinacy the activity of GABA-T, succinate dehydrogenase and aspartate transaminase was reduced while that of LDH and alanine transaminase was increased. The administration of fusarinic acid (100 mg/kg i. p.) to control animals induced a sharp increase of GAD activity in both structures of the brain. The stimulatory effects of fusarinic acid were not observed when it was administered to animals receiving alcohol chronically. Motor activity or rats was markedly reduced during chronical alcoholism and the first days of alcohol abstinacy (24--48 h), as well as following injection fusarinic acid and homopantothenic acid. The increase of locomotion and the vertical component of motor activity was observed only following one week or one month after alcohol abstinacy.
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PMID:[Adaptive changes in brain metabolism during chronic alcoholic intoxication]. 57 38

The effects of aminooxyacetic acid (AOAA), an aspartate aminotransferase (AAT) inhibitor, L-canaline, an ornithine aminotransferase inhibitor, and gamma-acetylenic GABA and gabaculine, both gamma-aminobutyric acid transaminase (GABA-T) inhibitors, on the release of aspartate from slices of rat medulla oblongata and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2(+)-dependent stimulus-evoked release of endogenous aspartate. AOAA (10(-4) and 10(-3) M) decreased the evoked release of aspartate in the medulla oblongata but not in the hippocampus. In addition, AOAA produced a decrease in the spontaneous efflux and tissue content of aspartate in the medulla oblongata. L-Canaline (5 x 10(-5) M), gamma-acetylenic GABA (10(-4) M) and gabaculine (10(-5) M) did not affect the evoked release of aspartate in the medulla oblongata, while these agents produced a decrease in spontaneous efflux and tissue content of aspartate. These findings suggest that AAT participates in the synthesis of transmitter aspartate in the medulla oblongata of the rat. It appears that there are the pools of transmitter aspartate and non-transmitter aspartate in the rat medulla oblongata.
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PMID:Electrical stimulation-evoked release of endogenous aspartate from rat medulla oblongata slices. Effects of inhibitors of aspartate aminotransferase and GABA transaminase. 234 2

The enzymatic activities of aspartate aminotransferase, GABA-transaminase and acetylcholinesterase were studied by means of histochemical methods in the mesencephalic trigeminal nucleus (MTN) neural complex of the turtle Mauremys caspica. Light microscope observations have demonstrated that MTN neurons have a positive reaction for these enzymes.
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PMID:Light microscope study of the enzymatic activities of aspartate aminotransferase, GABA transaminase and acetylcholinesterase in the mesencephalic trigeminal nucleus neural complex of Mauremys caspica. 237 32

An investigation of several neurochemical consequences of exposure of the rat to 3/4 of the estimated single injection LD50 quantity of trimethyltin chloride (TMT) indicated that a significant elevation in the levels of glutamine (Gln) and 5-hydroxyindole acetic acid (5-HIAA) occurred at post-dosing day 7 in each examined region of the brain; elevated Gln persisted in the hippocampus through day 14 and returned to control levels at day 28. At post-dosing day 7, levels of glutamate were decreased in the hippocampus, while levels of GABA were decreased in hippocampus and frontal cortex, but not in corpus striatum; hippocampal glutamate and GABA returned to control levels by post-dosing day 14. Decreased levels of taurine (Tau) occurred on day 7 in both hippocampus and frontal cortex; hippocampal Tau remained below control levels through post-dosing day 28. Levels of other amino acids and of amines and amine metabolites were not altered by TMT in the 7 to 28 day post-dosing interval. At day 7, TMT treatment did not alter brain regional activities of glutamine synthetase; however, plasma ammonia was elevated 100% above the control value. Alterations in several serum enzymes (esp., alkaline phosphatase and aspartate aminotransferase) revealed several other peripheral consequences of TMT exposure which persist through post-dosing day 28. The more prominent and wide-spread neurochemical alterations resulting from TMT exposure appear to reflect consequences of hyperammonemia resulting from a peripheral effect of the organotin compound.
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PMID:Trimethyltin-induced alterations in brain amino acids, amines and amine metabolites: relationship to hyperammonemia. 243 91

In astrocytes grown in primary cultures from cerebral cortex of neonatal rats, alpha 1-adrenoceptors regulate the active uptake of glutamate followed by an activation of glutamic oxaloacetate transaminase (GOT; EC 2.6.1.1.) and a slight activation of glutamine synthetase (GS; EC 6.3.1.2.) activity. The beta-adrenoceptors regulate the active uptake of GABA, and this is followed by an activation of gamma-aminobutyric acid alpha-ketoglutarate transaminase (GABA-T; EC 2.6.1.19.). The data suggest that astrocyte adrenoceptors may modulate neurotransmitter induced neuronal excitability.
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PMID:Regulation of glutamate and GABA transport by adrenoceptors in primary astroglial cell cultures. 256 1

Although alcoholic intoxication is attributed to its pharmacological effects on the cell membranes in brain, the rapid metabolic utilisation of the same alters the metabolism of brain affecting the metabolism of glutamate and GABA which have varied metabolic roles besides serving a major proportion of synaptic activity. A study on the effects of ethanol, both acute and short-term, on glutamate (glu) and GABA metabolism in various regions of rat brain was carried out. Increased activities of glutamic acid decarboxylase (GAD) and aspartic acid aminotransferase (AST) in all brain regions, but decreased activity of glutamic acid dehydrogenase (GDH) in cerebral cortex (CC) and cerebellum (CB) following ethanol administration in brain was observed. Differential effects of ethanol were also obtained on the contents of glu and aspartate (asp), which were increased in CC, CB, and brain stem (BS) regions, as opposed to GABA content, which, although found to increase in acute toxicity, showed a decrease in all of the above brain regions in short-term toxicity. It is concluded that the above changes in glu, asp and GABA represent the consequences of metabolic utilization of alcohol in the brain, probably more a state of cerebral excitation than depression, and the changes may be a compensatory phenomenon.
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PMID:Acute and short term effects of ethanol on the metabolism of glutamic acid and GABA in rat brain. 285 37

The role played by the inhibitory transmitters, GABA, glycine and taurine, and by excitatory (aspartate/glutamate) antagonists in mediating anticonvulsant action will be documented. This study provides examples of one anticonvulsant compound that affects glycine metabolism (milacemide), and another that affects aspartate metabolism (beta-methylene-aspartate). Beta-Methylene-aspartate, a selective inhibitor of glutamate-aspartate transaminase activity, protects against sound-induced seizures in audiogenic DBA/2 mice, with an ED50 value of 1.9 mumoles (icv; clonic phase). Forebrain and cerebellar aspartate, glutamate and GABA levels are reduced by 15-30% following the administration of beta-methylene-aspartate. Milacemide, a glycinamide derivative with experimental and clinical anticonvulsant activity, is ineffective against sound-induced seizures in DBA/2 mice. Following the ip administration of milacemide (100 mg/kg; 3 hours) there were significant increases in rat brain glycine levels in the cerebellum (+137%), cortex (+45%) and hippocampus (+59%).
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PMID:Anticonvulsant drug action and regional neurotransmitter amino acid changes. 290 57

A severe compression craniocerebral trauma was induced in rats under short-term halothane anesthesia. The activity of pyruvate and 2-oxoglutarate dehydrogenase complexes reduced significantly in the tissue of the damaged hemisphere, ALT activity increased sharply, AST activity grew slowly, the production of GABA in the glutamate decarboxylase reaction was slightly inhibited and its utilization in the GABA transaminase reaction was clearly accelerated. The GABA level in the nerve tissue showed a tendency to reduce, while the glutamate level had a tendency to increase. The observed changes are evidence that the inclusion of the GABA skeleton in the reaction of further oxidation intensifies, which may be of significance in compensation of the transport of the energetically oxidizing succinate and, possibly, in the formation of endogenous GABA possessing a stress-relieving effect.
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PMID:[The compensatory function of a GABA shunt in brain energy metabolism in measured craniocerebral trauma in rats]. 290 62

We measured amino acid contents in the brains of 11 patients with dominantly inherited cerebellar disorders. Despite clinical similarities, three biochemically different disorders were found. One disorder, with demonstrated HLA linkage in one pedigree, was characterized by moderate reduction of aspartate and glutamate contents in cerebellar cortex alone. In a second disorder, aspartate and glutamate contents were reduced markedly in other brain areas as well as in cerebellar cortex. Aspartate and glutamate contents were normal in cerebellar cortex in the third disorder. GABA content in cerebellar cortex and dentate nucleus was reduced in some patients with each disorder, whereas cerebellar taurine content was normal in all patients. Aspartate deficiency in cerebellar cortex did not result from lack of aspartate aminotransferase or pyruvate carboxylase activity. These amino acid abnormalities probably imply loss of specific cerebellar neurons.
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PMID:Neurotransmitter amino acids in dominantly inherited cerebellar disorders. 611 Oct 44


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