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:4.1.1.15 (glutamate decarboxylase)
2,169 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amino acid concentrations were measured in the cortex, cerebellum and hippocampus of the mouse brain before and during seizures induced by isoniazid (250 mg/kg i.p.), an inhibitor of L-glutamate-1-decarboxylase (EC 4.1.1.15: GAD). Valproate sodium and diazepam dose-dependently delay the onset of convulsive fits caused by isoniazid. However, neither diazepam nor valproate prevented the decrease in GABA concentrations produced by isoniazid alone. Also, these antiepileptic drugs did not modify the rate of GABA depletion elicited by isoniazid. These results, observed in four different brain structures, strengthen those first obtained with beta-vinyllactic acid, another inhibitor of GAD.
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PMID:The specific protective effect of diazepam and valproate against isoniazid-induced seizures is not correlated with increased GABA levels. 393 Jun 61

Young (8 month) and aged (27-28 month) male C57BL/6J mice were trained in a spatial discrimination task requiring working memory. The mice were tested during three trials daily in an eight-arm radial maze for 36 test days. Correct choices were reinforced with isotonic saline. In contrast to past reports, young mice learned the task. Old mice also learned the task, and no significant age-related differences in performance were observed. Following maze training, the mice were killed, the brains removed, and the specific activities of choline acetyltransferase (E.C.2.3.1.6., ChAT) and L-glutamic acid decarboxylase (E.C.4.1.1.15., GAD) were assayed in the hippocampus, and in frontal, sensorimotor, and cingulate areas of the cerebral cortex. The activities of these neurotransmitter synthetic enzymes did not differ significantly between young and old mice. Correct responding in the radial maze was positively correlated to ChAT activity in the cingulate cortex and negatively correlated to ChAT activity in the sensorimotor cortex. There was a similar pattern of correlation between performance and regional GAD activity, although none of the correlations involving GAD reached statistical significance.
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PMID:Radial maze performance in young and aged mice: neurochemical correlates. 398 22

1. DL-C-Allyglycine, 4-deoxypyridoxine hydrochloride and 3-mercaptopropionic acid have been studied with reference to their convulsant effects in mice and in baboons (Papio papio) with photosensitive epilepsy, and their action on the cerebral enzyme synthesizing gamma-aminobutyric acid (L-glutamate-1-carboxy-lyase).2. In mice, the ED(50) values for seizures following intraperitoneal injection were allylglycine 1.0 mmol/kg body weight, 4-deoxypyridoxine 1.1 mmol/kg and 3-mercaptopropionic acid 0.27 mmol/kg. Latency to seizure onset was longest after allylglycine (44-240 min), intermediate after 4-deoxypyridoxine (9-114 min) and shortest after 3-mercaptopropionic acid (2.5-8 min).3. In Papio papio intravenous administration of subconvulsant doses of allylglycine (0.87-3.1 mmol/kg), or of 4-deoxypyridoxine (0.21-0.53 mmol/kg) enhanced the occurrence and persistence of myoclonic responses to intermittent photic stimulation, and augmented the associated electroencephalographic abnormalities, without modifying their character or distribution. Higher doses produced brief seizures recurring at regular intervals, between 2-14 h after allylglycine (4.0-4.3 mmol/kg) or 1-4 h after 4-deoxypyridoxine (0.53-0.87 mmol/kg). Electroencephalographically these seizures originated unilaterally in the occipital or posterior parietal cortex.4. In Papio papio photically-induced epileptic responses were enhanced 5-10 min after the intravenous injection of 3-mercaptopropionic acid (0.09-0.28 mmol/kg). A sequence of brief generalized seizures followed by complete recovery occurred 4-17 min after the injection of 3-mercaptopropionic acid (0.28-0.38 mmol/kg). Fatal status epilepticus followed the injection of 3-mercaptopropionic acid (0.57-0.75 mmol/kg). E.E.G. records showed generalized cortical involvement at the onset of the seizures.5. L-Glutamate 1-carboxy-lyase (GAD) activity was determined in whole brain homogenates from mice killed at various intervals after receiving i.p. a convulsant dose of one of the compounds. Inhibition of GAD activity was evident 30-60 min before seizure onset following allylglycine or 4-deoxypyridoxine administration, and was maximal (40-60%) just before or during seizure activity. Addition of pyridoxal phosphate to the brain homogenate relieved inhibition produced by 4-deoxypyridoxine but not that produced by allylglycine. Inhibition of GAD activity in brain homogenates from animals killed 2 or 4 min after injection of a convulsant dose of 3-mercaptopropionic acid varied from 0-49% depending on the dose of 3-mercaptopropionic acid and the concentration of substrate in the assay system.6. Kinetic analysis of the inhibition of GAD activity following direct addition of the compounds to mouse brain homogenates indicated that 3-mercaptopropionic acid (0.01-0.5 mM) was competitive with respect to the substrate. A comparable percentage inhibition of GAD activity was obtained only with much higher concentrations of 4-deoxypyridoxne, i.e. 10-50 mM. Allylglycine in vitro was a very weak inhibitor of GAD activity.7. Three biochemically different mechanisms underlie the inhibition of cerebral GAD activity that precedes seizures induced by ailylglycine, 4-deoxypyridoxine and 3-mercaptopropionic acid. The data are consistent with a critical reduction in the rate of synthesis of gamma-aminobutyric acid being responsible for the onset of seizures.
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PMID:Seizures induced by allylglycine, 3-mercaptopropionic acid and 4-deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase. 420 45

Activities of the neurotransmitter synthetic enzymes, choline acetyltransferase (EC 2.3.1.6; ChAT), glutamic acid decarboxylase (EC 4.1.1.15; GAD), and tyrosine hydroxylase (EC 1.14.3.2; TH), were assayed in four brain regions of A/J and C57BL/6J mice at three ages (4, 18, and 24 months). The brain regions assayed were the fronto-parietal cortex, hippocampus, striatum, and cerebellum. Strain effects: In some brain regions, at several ages, ChAT activity did not differ among the two strains. However, ChAT was higher in the C57BL/6J strain in the cortex at 18 months, the hippocampus at 18 and 24 months, the striatum at 24 months, and the cerebellum at 4 months. The reverse was true in the cerebellum at 24 months, where ChAT was higher in A/J mice. GAD activity in C57BL/6J mice compared to that of A/J mice was higher in the striatum and cortex, and lower in the hippocampus and cerebellum. TH activities in all four regions were generally higher in C57BL/6J mice than in A/J mice. Age effects: Age differences in enzyme activities varied with the genetic strain. ChAT activity generally was higher in brain regions of older mice of both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age and strain comparisons of neurotransmitter synthetic enzyme activities in the mouse. 613 17

Uptake, synthesis, storage, and release of gamma-aminobutyric acid (GABA) are some of the characteristic properties of GABA-ergic neurons. In the present study, we have used these properties as physiological probes to follow the emergence and maturation of GABA-ergic neurons during postnatal development of the rabbit retina. There is autoradiographic, immunocytochemical, and pharmacological evidence that some amacrine cells and certain neurons in the ganglion cell layer probably use GABA as the neurotransmitter. These neurons take up GABA, contain the GABA-synthesizing enzyme L-glutamic acid decarboxylase (GAD, EC 4.1.1.15), and release the accumulated GABA by a CA++-dependent mechanism when depolorized with high extracellular K+ concentration. In this study, we show that certain neurons in the newborn retina already possess a specific mechanism for GABA uptake. The positions and numbers of these cells in the developing retina suggest that they will become GABA-ergic neurons in the adult retina. These putative GABA-ergic neurons are, however, probably immature at birth because newborn retinas contain only low levels of GABA and GAD. Additionally, there is relatively little K+-stimulated, Ca++-dependent release of (3H)-GABA from the newborn retinas. GABA concentrations and GAD activities in developing retinas increase steadily postnatally, reaching about 80% of the adult levels by day 9. The activities of the GABA-degrading enzyme, GABA-glutamate transaminase (GABA-T, EC 2.6.1.19), follow a similar pattern of maturation during retinal development. K+ stimulated GABA release, however, remains low until about day 6, and then increases dramatically from 20% to 85% of the adult level over the next 3 days. Taken together, our results indicate that in the rabbit retina, the commitment by certain neurons to use GABA as the transmitter is made prenatally. These neurons are immature at birth but are biochemically, physiologically, and probably functionally mature by about 9 days after birth.
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PMID:Postnatal development of GABA-ergic neurons in the rabbit retina. 625 33

Glutamate decarboxylase (L-glutamate 1-carboxylase, (EC 4.1.1.15) activity increased 7-fold during the course of differentiation of retina cell aggregate cultures prepared from 8-day-old embryos. The addition of 5 mM GABA in the culture medium almost completely prevented the appearance of GAD activity normally observed during the differentiation of the aggregates. This effect was readily reversible after shifting the aggregates to a GABA-free medium. Differentiated cultures, characterized by high GAD specific activity were also sensitive to GABA treatment, which promoted 50% decrease in the enzyme activity after 7 h incubation of the aggregates in the presence of 0.01 mM GABA. Maximal inhibition was obtained at 0.1 mM GABA. However, GABA up to 10 mM concentration had no effect on GAD activity when added directly to homogenates of retinal tissue. The GABA-mediated inhibition of GAD was antagonized by picrotoxin. The ED50 for picrotoxin to revert GAD inhibition by 0.01 mM GABA was approximately 2 microM. The time course for the decay in GAD activity of cultures exposed to 5 mM GABA, revealed two first-order kinetic components. For an 8-day-old culture the first component had a T1/2 of approximately 60 min and the second decayed with a T1/2 of approximately 315 min. In 13-day-old cultures the first component of GAD decay was identical to the one observed in 8-day-old cultures. The second component, however, was insensitive to GABA inhibition.
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PMID:GABA-mediated control of glutamate decarboxylase (GAD) in cell aggregate culture of chick embryo retina. 632 78

We have used an antiserum to L-glutamic acid decarboxylase ((GAD), a synthesizing enzyme for gamma-aminobutyric acid (GABA)) to localize putative GABAergic neurons in the developing C57BL/6J mouse retina. At early developmental stages (embryonic day 17 to postnatal day 3), strong GAD-like immunoreactivity is detectable in cell bodies located within the neuroblastic layer. These cells have relatively large cell bodies and extend several sturdy processes which are oriented radially at these early stages. We have identified these cells as horizontal cells. In addition, cell bodies adjacent to the inner plexiform layer and both diffuse and punctate structures within the inner plexiform layer proper have weak GAD-like immunoreactivity at this time. By postnatal day 6, GAD-positive horizontal cell processes begin to form a horizontal network in the newly formed outer plexiform layer. Immunolabeling of amacrine cell bodies and of punctate structures in the inner plexiform layer becomes much stronger at this time, reaching a maximum staining intensity during the second postnatal week. After postnatal day 12, GAD-like immunoreactivity of the horizontal cells begins to decline; in 4-week-old mice the horizontal cells are no longer detectably labeled by this GAD antiserum. At the same time, the GAD-like-immunoreactive material in the inner plexiform layer becomes stratified, forming distinct layers. Amacrine cells and the inner plexiform layer remain GAD positive into adulthood.
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PMID:Horizontal cells of the mouse retina contain glutamic acid decarboxylase-like immunoreactivity during early developmental stages. 650 14

The interactions of two forms of porcine brain glutamate decarboxylase (beta-GAD and gamma-GAD) with the effector ATP were studied by affinity chromatography. A third form, alpha-GAD, was only slightly retarded by the affinity matrix and was eluted in the buffer wash. The interaction of GAD with the ATP affinity matrix was qualitatively similar to its interaction with free ATP as reported in previous kinetic studies. The rank order of adenine nucleotides as eluting agents and affinity ligands was ATP greater than ADP greater than AMP. GAD was also eluted by its cofactor, pyridoxal 5'-phosphate, and this was enhanced by 1 mM Pi. In contrast, a high concentration (140 mM) of Pi by itself was required to elute the enzyme. GAD remained active while bound to the affinity column and was eluted in the holoenzyme form by ATP, indicating that the affinity ligand did not bind in the active site and did not displace catalytically active cofactor from the enzyme.
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PMID:Binding of ATP to brain glutamate decarboxylase as studied by affinity chromatography. 672 28

Three forms of glutamate decarboxylase from hog brain (termed alpha-, beta-, and gamma-GAD) were separated by hydrophobic interaction chromatography on phenyl-Sepharose, by isoelectric focusing, and by polyacrylamide gel electrophoresis. When rechromatographed on phenyl-Sepharose, each form migrated as a single entity, indicating that the forms are not readily interconvertible. The three forms are not different-sized aggregates of one form, since all three have the same approximate molecular weight (100,000) as determined by Sephadex G-200 chromatography. The pIs of the three forms separated by phenyl-Sepharose were determined by isoelectric focusing. The values obtained (5.3, 5.5, and 5.8 for alpha-, beta-, and gamma-GAD, respectively) were comparable to the pIs of the three peaks of activity observed upon focusing of enzyme that had been subjected to phenyl-Sepharose chromatography. These results indicate that phenyl-Sepharose chromatography and isoelectric focusing separate the same three components. When synaptosomal extracts were analyzed by phenyl-Sepharose chromatography without intervening purification steps, all three forms were present, but the proportion of beta-GAD was somewhat higher and that of gamma-GAD somewhat lower than in the usual preparations.
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PMID:Multiple forms of glutamate decarboxylase in porcine brain. 683 43

Taurine neurons in the cerebellum of rabbit, rat, and mouse were localized at the light microscope level by using polyclonal antibodies against cysteine sulfinic acid decarboxylase (CSADCase; EC 4.1.1.29), the enzyme responsible for the conversion of cysteine sulfinic acid to hypotaurine and of cysteic acid to taurine. The indirect peroxidase-antiperoxidase method was used on Vibratome sections and on serial sections of paraffin-embedded tissue. Intensification of CSADCase immunoreactivity was achieved by pretreatment of the animal with L-cysteine or L-cysteic acid intravenously 1-2 hr prior to perfusion. A combination of L-cysteic acid and demecolcine, which retards axoplasmic flow, was most effective in maximizing CSADCase immunoreactivity. Although these treatments intensified immunoreactivity in neurons, no more cells were reactive than in untreated controls. L-Glutamic acid did not increase CSADCase immunoreactivity but did increase immunoreactivity with antibodies against L-glutamic acid decarboxylase (GAD; EC 4.1.1.15), the synthetic enzyme for gamma-aminobutyric acid. Specificity was established by negative results obtained with various control incubations including the use of CSADCase antiserum preabsorbed with the antigen. Taurine neurons of the cerebellar cortex are arranged in sagittal microbands, defined by intensely CSADCase-reactive Purkinje neurons and their axons and dendrites, together with stellate, basket, and Golgi cells and their processes. In the vermis there is a narrow midline band, flanked laterally by three wider bands on either side, each separated from the next by an unreactive zone. Although the zonal borders are sharp, the interzonal areas contain some CSADCase-immunoreactive axons but no cell bodies. The seven vermal bands are best observed in the anterior lobe. Others exist in the lateral hemispheres. The paraflocculus and flocculus contain numerous intensely immunoreactive neurons, and banding is difficult to discern. Lobule X of the vermis is also heavily endowed with taurine neurons. Numerous large and medium-sized deep cerebellar and vestibular nuclei are also immunoreactive. These observations indicate that cerebellar neurons are chemically heterogeneous but that neurons of similar chemical signature in the cerebellar cortex are organized into sagittal microbands. This corroborates our earlier evidence that Purkinje cells containing motilin and those containing both motilin and gamma-aminobutyric acid are also arranged in vermal sagittal microbands. The midline vermal band contains Purkinje neurons with multiple neuroactive substances-taurine, gamma-aminobutyric acid, and motilin. It remains to be determined how this chemical zonation in the cerebellar cortex relates to the banded afferent innervation from spinal, vestibular, reticular, and olivary sources.
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PMID:Sagittal cerebellar microbands of taurine neurons: immunocytochemical demonstration by using antibodies against the taurine-synthesizing enzyme cysteine sulfinic acid decarboxylase. 695 97


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