Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of certain key enzymes involved in glutamic acid metabolism was studied in purified brain mitochondria and in mitochondrial subfractions separated in a discontinuous 1.2--1.6 mol/l sucrose gradient. Alanine aminotransferase and glutamate dehydrogenase were found to be matrix enzymes and aspartate aminotransferase to be associated with the inner mitochondrial membranes. After the purified mitochondria had been separated into 5 subfractions, aspartate aminotransferase and NAD+-dependent isocitrate dehydrogenase were found to be bound to the lighter mitochondrial subfractions settling at the 1.4--1.5 mol/l sucrose boundary while alanine aminotransferase, 4-aminobutyrate transaminase and glutamate dehydrogenase were associated with the heavier subfractions settling below 2.4 mol/l sucrose. The highest specific activity of the given enzymes was found in the subfraction settling at the 1.4--1.5 mol/l sucrose boundary, the only exception being alanine aminotransferase activity, whose maximum was found in the subfractions settling in 1.5 and 1.6 mol/l sucrose. It was concluded that alanine aminotransferase, in conjunction with glutamate dehydrogenase, is linked to NH3 binding and to the oxidation of reduced adenine nucleotides; in addition, alanine aminotransferase is presumed to have the function of transporting glutamate from the mitochondria to the extramitochondrial space.
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PMID:Alanine aminotransferase and some other enzymes in different populations of free brain cortex mitochondria. 645 52

The reaction of muscimol as amino donor substrate for GABA transaminase (GABA-T) has been studied using enzyme purified from rabbit brain. Enzyme activity was assayed by measuring the glutamate produced using glutamate dehydrogenase. Kinetic parameters determined at 37 degrees C were for GABA, Km (app) = 1.92 +/- 0.24 mM, specific activity = 7.33 +/- 0.27 mumol/min/mg (kcat = 13.7s-1), and for muscimol, Km (app) = 1.27 +/- 0.15 mM, specific activity = 0.101 +/- 0.009 mumol/min/mg (kcat = 0.19s-1). Addition of muscimol to the enzyme caused the spectral changes associated with conversion of the pyridoxaldimine form to the pyridoxamine form, and the first-order rate constant for the reaction showed a dependence on muscimol concentration that followed saturation kinetics, with a K = 1.1 +/- 0.18 mM and kmax = 0.065 +/- 0.004 s-1 (19 degrees C). The rate of spectral change observed on addition of muscimol to ornithine transaminase was extremely slow--at least an order of magnitude slower than that seen with GABA-T.
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PMID:Reaction of muscimol with 4-aminobutyrate aminotransferase. 664 8

It had previously been shown that dissociated cell cultures from chick embryo spinal cord have a high affinity uptake system for the neurotransmitter gamma-aminobutyric acid (GABA) and make functional inhibitory synaptic contacts as determined by electrophysiology (Farb et al., 1979). It is shown here that these cultures can synthesize GABA from added glutamate in a glutamate decarboxylase-dependent reaction. Furthermore, these cultures have a functional GABA transaminase that degrades the neurotransmitter. This enzyme can be specifically and irreversibly blocked with gabaculine. A 15 min incubation with 10(-6) M-gabaculine completely inactivates the enzyme. The inactivation of the enzyme leads to an increase in GABA levels. Long-term incubation (16 days) of gabaculine in the medium does not appear to alter high affinity GABA transport, suggesting that the drug is not toxic to cells capable of accumulating GABA.
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PMID:The inactivation of gamma-aminobutyric acid transaminase in dissociated neuronal cultures from spinal cord. 720 86

In an attempt to characterize the effect of estrogens and progesterone on retinal GABA metabolism, female Wistar Nossan rats were ovariectomized and treated for three days with 17 beta-estradiol (1 microgram/day), estrone (2 micrograms/day), estriol (200 micrograms/day) and progesterone (500 micrograms/day) or vehicle. After 3 days of steroid hormones treatment, GAD, GABA-T activities and GABA content were measured in retina homogenate. Progesterone did not reduce GAD, GABA-T activities and GABA content from ovariectomized levels. 17 beta-estradiol, estrone and estriol decreased the GAD activity. Furthermore the decrease in GAD activity was maximal for 17 beta-estradiol whereas the estrogens treatment was ineffective on GABA-T. GABA content was significantly decreased only by 17 beta-estradiol. Estrogens reduced the Vmax of GAD for glutamate as a substrate without changing the Km.
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PMID:Effects of estrogens and progesterone on GABA system in ovariectomized rat retina. 729 12

The great interest in new compounds able to increase GABA concentration in the brain as potential antiepileptic drugs has led to the synthesis of powerful inhibitors of GABA transaminase (GABA-T) e.g. gamma-acetylenic GABA (GAG) and gamma-vinyl-GABA. Present experiments were aimed to study behavioral, electrocortical and biochemical effects of GAG after its intraventricular injection. It has been shown that in chicks the microinjection of GAG into the third cerebral ventricle produced a biphasic behavioral and electrocortical syndrome : an initial phase of behavioral and electrocortical sleep followed by a paradoxycal increase in motor activity and a very intense behavioral and ECoG arousal pattern. In addition intraventricular GAG (0.8 mumol) produced a significant increase 1 and 2 h later in GABA concentration in the diencephalon and brain-stem whereas no changes occurred in other brain areas e.g. cerebral hemispheres, optic lobes. Higher doses (1.6 mumol), produced after 1 h, concomitantly to the increased GABA concentration, a significant GABA-T inhibition and a profound inhibition of glutamate-decarboxylase in the diencephalon and brain-stem. Present experiments may explain the paradoxical behavioral, motor and electrocortical stimulation observed at the time of GABA increase concentration and suggest that a small functional neuronal pool of GABA, more than the whole absolute levels of GABA in a given area of the brain, seems to be involved in the control of GABAergic mediated inhibitory mechanisms.
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PMID:Effects of intraventricular gamma-acetylenic-GABA on GABA concentrations, GABA-T and GAD in several areas of the chick brain. 732 72

The oxidation of 4-aminobutyric acid (GABA) by nonsynaptosomal mitochondria isolated from rat forebrain and the inhibition of this metabolism by the branched-chain fatty acids 2-methyl-2-ethyl caproate (MEC) and 2.2-dimethyl valerate (DMV) were studied. The rate of GABA oxidation, as measured by O2 uptake, was determined in medium containing either 5 or 100 mM-[K+]. The apparent Km for GABA was 1.16 +/- 0.19 mM and the Vmax in state 3 was 23.8 +/- 5.5 ng-atoms O2 x min-1 x mg protein-1 in 5 m M-[K+]. In a medium with 100 mM-[K+] the apparent Km was 1.11 +/- 0.17 mM and Vmax was 47.4 +/- 5.7 ng-atoms O2 x min-1 x mg protein-1. The Ki for MEC was determined to be 0.58 +/- 0.24 or 0.32 +/- 0.08 mM, in 5 or 100 mM-[K+], respectively. For DMV, the Ki was 0.28 +/- 0.05 or 0.34 +/- 0.06 mM, in 5 or 100 mM-[K+] medium, respectively. The O2 uptake of the mitochondria in the presence of GABA was coupled to the formation of glutamate and aspartate; the ratio of oxygen uptake to the rate of amino acid formation was close to the theoretical value of 3. Neither the [K+] nor any of the above inhibitors had any effect on this ratio. The metabolism of exogenous succinic semialdehyde (SSA) by these same mitochondria was also examined. The Vmax for utilization of oxygen in the presence of SSA was much greater than that found with exogenously added GABA, indicating that the capacity for GABA oxidation by these mitochondria is not limited by SSA dehydrogenase. In addition, the branched-chain fatty acids did not inhibit the metabolism of exogenously added SSA. Thus, the inhibitors examined apparently act by competitively inhibiting the GABA transaminase system of the mitochondria.
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PMID:Oxidative metabolism of 4-aminobutyrate by rat brain mitochondria: inhibition by branched-chain fatty acid. 745 35

The glutamine cycle has been proposed as a pathway in which glutamine synthesized in glia provides substrate for synthesis of the neurotransmitters glutamate and GABA as they are lost from neurons. To test whether GABA may regulate this pathway, the effect of elevated GABA on the glial enzyme glutamine synthetase was examined in rat brain. Repeated subcutaneous injections of the antiepileptic GABA transaminase inhibitor gamma-vinylGABA at a dose of 150 mg/kg per day for 21 days reduced glutamine synthetase activity by 36% in the cortex and 22% in the cerebellum. At 30 mg/kg per day, glutamine synthetase activity was reduced by 9.5% in the cortex but unchanged in the cerebellum. The reductions were brain specific because the skeletal muscle and liver enzymes were unaffected by gamma-vinylGABA administration. Amino acid analysis of the cortex from gamma-vinylGABA-treated rats demonstrated a 270% increase in GABA levels after 150 mg/kg but no change after 30 mg/kg. GABA levels and glutamine synthetase activity were inversely correlated. The 150 mg/kg dose significantly lowered cortical glutamine and glutamate levels. The decline in brain glutamine synthetase activity with chronic gamma-vinylGABA administration developed gradually over time and may be due to the slow turnover of this enzyme in vivo.
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PMID:Repeated administration of gamma-vinylGABA reduces rat brain glutamine synthetase activity. 779 Aug 80

The effect of aminooxyacetic acid (AOAA), an inhibitor of pyridoxal phosphate-dependent enzymes (including the aminotransferases), on the K(+)-evoked release of amino acids was studied during microdialysis of neostriatum in anesthetized rats. K(+)-evoked (100 mM) release of aspartate, glutamate, and GABA was inhibited by 74%, 70%, and 63%, respectively, by 20 mM Mg2+ and are therefore reflecting release from the transmitter pools of these amino acids. Treatment with AOAA decreased the K(+)-evoked release of aspartate, glutamate, and GABA instantly, with a delayed decrease in the efflux of glutamine and alanine, arguing that the synthesis of transmitter amino acids in particular is sensitive to the activity of pyridoxal phosphate-dependent enzymes. Interestingly, GABA release increased severalfold following the initial decrease, probably reflecting inhibition by AOAA on GABA aminotransferase, the enzyme most sensitive to inhibition by AOAA, and responsible for enzymatic inactivation of transmitter GABA.
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PMID:Evidence using in vivo microdialysis that aminotransferase activities are important in the regulation of the pools of transmitter amino acids. 809 92

Kinetics of uptake and release, rates of oxidation of glutamate and aspartate, activities of the enzymes of glutamate metabolism were studied in the mitochondrial, synaptosomal and cytosolic preparations of rat cerebellum. Transport of these amino acids into mitochondria was by a single low affinity carrier, whereas in synaptosomes both high and low affinity uptake systems were observed. The depolarization induced release of these amino acids from nerve terminals was observed to be calcium dependent. Mitochondria oxidized both these two amino acids at a higher rate than synaptosomes and the oxidation in cytosol was very minimal. Transamination appears to be the major reaction for the metabolism of glutamate and aspartate. Activities of GDH, GLNSE and GABA-T were highest in mitochondria, whereas activities of GS and GAD were highest in cytosol and synaptosomes respectively.
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PMID:Uptake, release and metabolism of glutamate and aspartate by rat cerebellar subcellular preparations. 809 41

The present review focuses on enzymes involved in the metabolism of amino acid neurotransmitters and the microphotometric determinations of their activities in various layers of the rat hippocampus. The enzymes are NAD-linked isocitrate dehydrogenase (NAD-ICDH), glutamate dehydrogenase (GDH), and GABA transaminase (GABAT), all of which are localized in mitochondria. GDH seems to be restricted to astrocytes, whereas NAD-ICDH and GABAT are localized in neurons as well as in astrocytes. NAD-ICDH is an important enzyme of the tricarboxylic acid cycle and may deliver alpha-ketoglutarate for the formation of glutamate and GABA, which serve as neurotransmitters in the hippocampus. GDH catalyses the interconversion of alpha-ketoglutarate and glutamate, whereas GABAT is the important GABA-degrading enzyme and requires alpha-ketoglutarate for its activity. While differing in their cellular distribution and activity levels, NAD-ICDH, GDH and GABAT are significantly correlated in their hippocampal distribution. Furthermore, developmental and pharmacohistochemical studies suggest that the distribution and activity of astrocytic GDH is correlated with amino-acidergic neurotransmission in the hippocampus. The data reported give further evidence for a metabolic relationship between neurons and astrocytes in the turnover and metabolism of glutamate and GABA.
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PMID:In situ measurements of enzyme activities in the brain. 810 May 59


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