Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The substrate-promoted inactivation of glutamate decarboxylase from hog brain was studied. Inactivation was a slow process that was dependent on the concentration of glutamate. Glutamate-dependent inactivation was not first order but was best described as the sum of two exponential decay processes. At 10 mM glutamate, the half-lives at 30 degrees C were about 6 min for the fast component and 70 min for the slow component. Glutamate-dependent inactivation appeared to be due to the formation of apoenzyme since the rate and extent of inactivation were greatly reduced by the presence of pyridoxal 5'-phosphate (the cofactor, pyridoxal-P). Also, inactivated enzyme could be reactivated by adding pyridoxal-P (Meeley and Martin, 1983). Micromolar concentrations of ATP enhanced glutamate-promoted inactivation in the absence of pyridoxal-P. ATP also enhanced inactivation in the presence of 10 microM pyridoxal-P, but somewhat higher concentrations were required for an equal effect. ATP had little or no direct effect on the enzyme in the absence of glutamate. In the absence of pyridoxal-P, Pi reduced the enhancement of inactivation by 10 microM but not by 750 microM ATP. Glutamate-promoted inactivation, its enhancement by ATP, and the opposition to inactivation by pyridoxal-P and Pi appear to be important in the regulation of glutamate decarboxylase.
Cell Mol Neurobiol 1983 Mar
PMID:Inactivation of brain glutamate decarboxylase and the effects of adenosine 5'-triphosphate and inorganic phosphate. 613 27

The effects of ATP and inorganic phosphate (Pi) on the reactivation of glutamate apodecarboxylase by its cofactor pyridoxal-5'-phosphate (pyridoxal-P) was studied. Apoenzyme was prepared by preincubation with glutamate. Apoenzyme prepared with glutamate alone was reactivated slowly and incompletely by adding a saturating concentration of pyridoxal-P (20 microM). Reactivation was slightly enhanced by 1-10 mM Pi. Reactivation by pyridoxal-P plus Pi was greatly enhanced by the presence of low concentrations (less than 100 microM) of ATP during the preparation of apoenzyme with glutamate. Reactivation was much lower if Pi was omitted. Enhancement of reactivation by ATP was due to its effect during apoenzyme formation, since ATP did not enhance reactivation if added only during reactivation and since the enhancing effect persisted after the removal of free ATP by chromatography on Sephadex G-25 after apoenzyme preparation and before reactivation. Reactivation was inhibited by high concentrations of ATP (greater than 100 microM), possibly by competition of ATP for the cofactor binding site. Four factors (glutamate, pyridoxal-P, ATP, and Pi) control a cycle of inactivation and reactivation that appears to be important in the regulation of brain glutamate decarboxylase.
Cell Mol Neurobiol 1983 Mar
PMID:Reactivation of substrate-inactivated brain glutamate decarboxylase. 613 28

The interaction of glutamate decarboxylase with the aspartate analogues 3-arsonoalanine and 3-phosphonoalanine, with the glutamate analogues 2-amino-4-arsonobutyric acid and 2-amino-4-phosphonobutyric acid, and with 4-(methylthio)-L-glutamic acid, both as a mixture of diastereoisomers and as the (2S,4R)-form, was studied. All these analogues were poor substrates for the enzyme and only weak inhibitors. Their decarboxylation was accompanied by transamination of the enzyme-bound pyridoxal phosphate (PLP) to pyridoxamine phosphate (PMP), thus inactivating the decarboxylase. With arsonoalanine only part of the PLP was converted into PMP.
Biochem Mol Biol Int 1995 May
PMID:The interaction of glutamate decarboxylase from Escherichia coli with substrate analogues modified at C-3 and C-4. 766 23

A tomato fruit cDNA library was differentially screened to identify mRNAs present at higher levels in fruit of the tomato ripening mutant rin (ripening inhibitor). Complete sequencing of a unique clone ERT D1 revealed an open reading frame with homology to several glutamate decarboxylases. The deduced polypeptide sequence has 80% overall amino acid sequence similarity to a Petunia hybrida glutamate decarboxylase (petGAD) which carries a calmodulin-binding site at its carboxyl terminus and ERT D1 appears to have a similar domain. ERT D1 mRNA levels peaked at the first visible sign of fruit colour change during normal tomato ripening and then declined, whereas in fruit of the ripening impaired mutant, rin, accumulation of this mRNA continued until at least 14 days after the onset of ripening. This mRNA was present at much lower levels in other tissues, such as leaves, roots and stem, and was not increased by wounding. Possible roles for GAD, and its product gamma-aminobutyric acid (GABA) in fruit, are discussed.
Plant Mol Biol 1995 Mar
PMID:A role for glutamate decarboxylase during tomato ripening: the characterisation of a cDNA encoding a putative glutamate decarboxylase with a calmodulin-binding site. 776 95

The mRNA levels encoding for the enzyme glutamate decarboxylase (GAD65) were measured by computerized image analysis after in situ hybridization histochemistry in the striatum and pallidum of normal and MPTP-treated squirrel monkeys. At striatal level, GAD65 mRNA labeling in MPTP-treated monkeys was primarily increased in the dorsolateral sector of the putamen. At pallidal level, the intensity of GAD65 mRNA labeling in single neurons was increased in the internal but not the external segment of the pallidum of MPTP-treated monkeys. The regulation of GAD65 mRNA levels in the striatum and internal segment of the pallidum suggest an important role for this enzyme in the regulation of GABAergic functions in basal ganglia.
Brain Res Mol Brain Res 1994 Sep
PMID:Glutamate decarboxylase (GAD65) mRNA levels in the striatum and pallidum of MPTP-treated monkeys. 780 34

This study was carried out to investigate whether the increase of GABA levels in spinal cord dorsal horn in response to chronic inflammatory lesions results from an enhanced expression of the gene that governs the production of glutamate decarboxylase (GAD), the enzyme responsible for GABA synthesis. In situ hybridization was used to visualize neurons expressing GAD mRNA within the spinal cord, in both intact rats and in animals bearing chronic monoarthritis induced by intraarticular injection of complete Freund's adjuvant. In control normal animals, neuronal labeling by an antisense oligonucleotide probe occurred throughout the spinal gray matter, except in the motoneuronal pool of Rexed's lamina IX. In treated animals 4 days after the induction of monoarthritis, a significant increase in the number of labeled cells occurred in the superficial laminae (25.3%) and the neck (17.2%) of the ipsilateral dorsal horn at segments L4-L5 which contain the projection domain of the ankle joint. At 2 weeks, values were, respectively, 20.2% and 13.9% over contralateral values, and an increase of 12.4% was found in the ventral horn. At 3 weeks, the ipsilateral increase of labeled cells was restricted to the superficial dorsal horn (15.2%). These findings emphasize the role played by the spinal GABAergic system in the modulation of chronic nociceptive input. It is suggested that the response of the spinal GABAergic system depends on the activation of GAD gene transcription in spinal neurons.
Brain Res Mol Brain Res 1994 Oct
PMID:Expression of GAD mRNA in spinal cord neurons of normal and monoarthritic rats. 785 44

The unique structures of process-bearing cells in the central nervous system (CNS) present an ideal model with which to study the differential distribution of mRNA. We conducted a side-by-side examination of the intracellular distribution of nine neural mRNAs by in situ hybridization histochemistry in mammalian brain and observed four general types of mRNA distributions. (1) Some mRNA species were confined to cell somas and included those encoding the glial proteins, myelin proteolipid protein and 2'3'-cyclic nucleotide-3'-phosphodiesterase and the neuronal enzymes, neuron-specific enolase and glutamate decarboxylase-67. (2) Some mRNAs were found abundantly within the cell soma and were also located throughout cellular processes. These included myelin basic protein (MBP) mRNA, which was localized to the cell soma and myelin sheaths of oligodendrocytes, and glial fibrillary acidic protein (GFAP) mRNA, which was localized to the cell soma and processes of reactive and some non-reactive astrocytes in the adult brain and radial glia in embryonic brain. (3) Some mRNAs were found primarily in perinuclear cytoplasm but in some cells were also observed in cell processes. These included mRNAs encoding the protein kinase C/calmodulin-binding substrates, RC3 (neurogranin) and GAP-43, which were identified in the somas as well as within the proximal dendritic branches of specific forebrain neurons. (4) Some mRNAs were localized primarily within cell processes. These included MAP2 mRNA, which was identified by deep staining within dendritic fields but by only light staining within neuronal cell bodies. The data also indicated that the stage of cellular development and the regional location of a cell within the CNS had a profound influence on translocation events. MAP2 mRNA was found in the dendritic processes of most neurons but was confined to the soma of neurons in specific brainstem nuclei. MBP mRNA was confined to the perinuclear cytoplasm of immature oligodendrocytes and was then transported into the myelin sheath at a developmental stage corresponding to myelination. The distribution patterns of these mRNAs are likely to reflect the mechanism by which the protein products of these molecules are targeted within neurons and glia. In addition, mRNA movement may be influenced by cellular and regional factors not encoded solely within the structure of the translocated mRNA.
Brain Res Mol Brain Res 1994 Nov
PMID:Cellular influences on RNA sorting in neurons and glia: an in situ hybridization histochemical study. 787 39

It was shown by electron microscopy, that the native molecule of glutamate decarboxylase is a hexamer with dihedral symmetry; the subunits are situated at the apices of an octahedron. Apoenzyme at pH 6.0 is dissociated form. It were found s20.w - 12.8 +/- 0.54S and 5.51 +/- 0.43S for the native hexamer and a dissociated form, respectively. By column gel-filtration the molecular mass of the dissociated form was estimated as 105-106 kDa, this value corresponds to a dimer. There were 10 buried SH-groups per subunit in the hexamer, after dimer formation 8 of them became accessible. The reversible hexamer-dimer dissociation depends on pH and PLP. The pH dependences of the enzyme dissociation and activity are very similar. In the result of adding of 6 PLP equivalents to the dimers the reactivation and hexamer assembly were reached, the SH-groups burying preceded both these reactions. Effect of pH and PLP on the quaternary structure is known for some other PLP-enzymes. It may be the additional proof for the idea of a common ancestor for PLP-enzymes.
Mol Biol (Mosk)
PMID:[Study of the quaternary structure of glutamate carboxylase from Escherichia coli]. 788 40

The C57BL/10 SPS/sps mouse mutant are audiogenic seizure-susceptible. The enzymatic activities of glutamate decarboxylase (GAD), GABA aminotransferase (GABA-T), alanine aminotransferase (ALA-T), aspartate aminotransferase (ASP-T), and glutamate dehydrogenase (GDH) of whole brain supernatant are significantly reduced in these epileptic mice. GABA uptake is decreased in cortex, midbrain, and pons medulla. Previous studies showed the presence of two sodium-dependent GLU uptake systems in normal (SPS/SP) mice. Glutamate Umax by System 1 is significantly decreased in these mice, whereas the Umax value for System 2 is significantly increased in the epileptic mice.
Mol Neurobiol
PMID:Altered GABAergic and glutamatergic transmission in audiogenic seizure-susceptible mice. 788 3

The expression of the autoantigen glutamate decarboxylase in islets of Langerhans was investigated under different culture conditions, which affect the functional activity of the beta-cell. Using immunoprecipitations and analyses of enzyme activity, an increase in glutamate decarboxylase was detected in rat islets cultured at a glucose concentration of 11 mmol/l compared with those cultured at 5.6 mmol/l glucose. To determine whether the change was induced at the level of mRNA expression, total RNA was extracted from rat islets cultured at 5.6 or 11 mmol/l glucose, reverse transcribed and amplified by the polymerase chain reaction. Comparative quantitation in a phosphor imager revealed a significantly higher (82%, P < 0.005) content of glutamate decarboxylase mRNA in islets cultured at 11 mmol/l glucose. In parallel, human recombinant interleukin-1 beta, and diazoxide were tested for their effects on the expression of glutamate decarboxylase. Islets cultured at 11 mmol/l glucose in the presence of 40 U/ml of interleukin-1 beta, showed a 63% decrease (P < 0.005) in enzyme activity compared with those cultured at 11 mmol/l glucose alone, and similar decreases were noted on analysis of glutamate decarboxylase biosynthesis and mRNA. Islets cultured at 11 mmol/l glucose in the presence of 22.5 mg/ml diazoxide exhibited a significant reduction in enzyme activity (59%; P < 0.001) compared with those cultured at 11 mmol/l glucose only. This reduction, however, was not accompanied by a decrease in the content of glutamate decarboxylase mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Jun
PMID:Regulation of GAD expression in islets of Langerhans occurs both at the mRNA and protein level. 792 71


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