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)

Glutaric aciduria is a disorcer of lysine, tryptophan, and hydroxylysine metabolism characterized by intermittent metabolic acidemia, dystonia, athetosis and mental retardation. It is due to a recessively inherited deficiency of glutaryl-CoA dehydrogeanse, the enzyme(s) which catalyze the dehydrogenation of glutaryl-CoA to glutaconyl-CoA and decarboxylation of the latter to crotonyl-CoA. Abnormal quantities of glutaric, beta-hydroxyglutaric, and glutaconic acids are found in the urine of these patients. The nature of the movement disorder prompted study of the effects of the abnormally excreted metabolites on brain glutamate decarboxylase, an enzyme implicated in the pathogenesis of Huntington's chorea. Glutamate decarboxylase activity was examined in rat and rabbit brain acetone powders, stabilized with pyridoxal phosphate and glutathione. Glutarate, beta-hydroxyglutarate, and glutaconate were competitive inhibitors of this emzyme, Ki values being 1.3 X 10(-3) mol/l, 2.5 X 10(-4) mol/l, respectively. This inhibition may explain the neurological accompaniments of this syndrome.
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PMID:Inhibition of brain glutamate decarboxylase by glutarate, glutaconate, and beta-hydroxyglutarate: explanation of the symptoms in glutaric aciduria? 124 44

We have recorded 1H NMR spectra in H2O for exchangeable protons of four pyridoxal phosphate-dependent enzymes: D-serine dehydratase, aspartate aminotransferase, tryptophan: indole-lyase and glutamate decarboxylase. The molecular masses range from 48-250 kDa. In every case there are downfield peaks which are lost when the apoenzyme is formed. In most cases some peaks shift in response to interactions with substrates and inhibitors and with changes in pH. We associate one downfield resonance with the proton on the ring nitrogen of the coenzyme and others with imidazole groups that interact with coenzyme or substrates. The chemical shift for the coenzyme-bound proton differs for free enzyme, substrate Schiff base or quinonoid forms.
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PMID:NMR spectra of exchangeable protons of pyridoxal phosphate-dependent enzymes. 206 76

The administration of GM1 ganglioside, 30 mg/kg per day i.p., begun 3 days prior to an intrastriatal injection of the excitotoxic tryptophan metabolite quinolinic acid (QUIN) and continued for 8-16 days thereafter, significantly decreased QUIN-induced striatal damage, as evaluated by measuring the activity of the marker enzymes, choline acetyltransferase and L-glutamic acid decarboxylase. Since an increased production of QUIN has been demonstrated in Huntington's chorea patients it is possible that repeated GM1 administration could reduce the occurrence of progressive striatal neuronal loss in this neurological disorder.
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PMID:Systemic treatments with GM1 ganglioside reduce quinolinic acid-induced striatal lesions in the rat. 261 75

In this study we have performed surgical, chemical and combined surgical/chemical lesions in order to elucidate neurotransmitter mechanisms in the superior colliculus (SC) of albino rats. Visual cortex (VC) ablation reduced high affinity (HA) uptake of D-Asp by 32% in the deafferented SC. Local injection of kainic acid (KA) into SC reduced HA D-Asp uptake selectively in the lower dose range (less than 1 nmol) by 50-60%. The GABAergic marker glutamate decarboxylase (GAD) was decreased by maximally 60% only at doses exceeding 2 nmol. Choline acetyltransferase (ChAT), however, was not affected at any of the doses administered. VC ablation provided an almost complete protection against 1 nmol KA. When KA was injected 2 days prior to VC ablation an additive effect on HA D-Asp uptake of the two lesions was observed. From these observations we infer that the notion of a glutamatergic projection from VC to SC has been strengthened. Moreover, local neurons in intermediate layers account for about 60% of the HA D-Asp uptake in SC, and these are most likely impinged upon by the glutamatergic afferents. The neurotoxic effects of KA were compared with those of some suspected endogenous excitotoxins, i.e. N-methyl tetrahydrofolic acid (Me-THF), other folates and the tryptophan metabolite quinolinic acid (QA). N-methyl tetrahydrofolic acid, Me-THF (4 and 10 nmol) reduced HA D-Asp uptake by about 50%, only when coinjected with ascorbic acid. GAD and ChAT were not affected at either of the doses. QA was about 100-fold less potent than KA on a molar basis, and the maximal reduction of GAD was similar in QA and KA injected animals, whereas the maximal reduction of HA D-Asp was only 40% after QA injection in SC. We conclude that Me-THF, QA and KA exert their neurotoxic actions by different mechanisms as judged by the behavioral, histopathological and biochemical sequelae seen after local injections of the respective substances in intermediate layers of SC and corroborate data obtained from other brain areas.
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PMID:Effects of kainic acid and other excitotoxins in the rat superior colliculus: relations to glutamatergic afferents. 287 52

The location of the Escherichia coli K-12 genes determining or regulating glutamate transport, and the location of the gene determining glutamate decarboxylase synthesis, were established by conjugation. The ability to grow on glutamate as the sole source of carbon and energy was used to select for glutamate transport recombinants. Two genes determining the ability to grow on glutamate as the sole source of carbon and energy were mapped. One (gltC) is located near mtl (mannitol), and the other (gltH) appears to be located between the gal (galactose) and trp (tryptophan) loci. The glutamate decarboxylase gene (gad) is strongly linked to gltC. The gltC(+) recombinants grow on glutamate much faster and accumulate this amino acid to a greater extent than do the gltH(+) recombinants. The gltH(+) gene functioned only in one female strain (P678), whereas the gltC gene functioned in all the female strains tested (P678, C600, W1).
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PMID:Genetic analysis of glutamate transport and glutamate decarboxylase in Escherichia coli. 534 Mar 10

Six groups of five female rats each aged 6 weeks at start were fed different diets for a period of 15 days. The protein sources of diets used were: a) 10% casein: b) wheat: c) Bengalgram: d) wheat + lysine: and e) Bengalgram + methionine + cystine + tryptophan, all containing 1.6 g nitrogen/100 g, and f) 20% casein (3.2 g nitrogen/100 g diet). The group of five rats fed a 10% casein diet served as control. It was observed that total brain RNA, protein and free alpha amino nitrogen content and protein/DNA ratio were significantly decreased on wheat and Bengalgram diets as compared to the control. The specific activities of glutamine synthetase, glutaminase I, glutaminase II and glutamate decarboxylase and concentrations of aspartic acid, glutamic acid, glutamine and gamma-aminobutyric acid (GABA) in the brain were also decreased on wheat and Bengalgram diets. The fortification of wheat with lysine and of Bengalgram with methionine, cystine and tryptophan did not alter brain weight and DNA content. While brain RNA, protein free alpha amino nitrogen (F alpha AN) and activities of enzymes of glutamic acid metabolism and related amino acid levels were restored, the activity of enzyme glutamine transferase and alanine concentration remained unaltered on various diets fed. The observations on 20% casein diet showed that levels were similar to those observed on 10% casein diet.
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PMID:Effect of wheat and Bengalgram diets on brain glutamate metabolism in postweanling rats. 615 61

The number of general biochemical and specific neurochemical activities have been investigated in postmortem human brain tissue in relation to the terminal state of the patient. Cases were broadly divided into those dying after a period of normal or near normal health (Category A) and those dying after a prolonged period of severe illness (Category B). Whilst most of the metabolic and transmitter-related enzymes, amino acids and neuropeptides investigated were not significantly different between the two groups, there were in Category B highly significant reductions in glutamate decarboxylase, phosphofructokinase and tissue pH, and increases in several amino acids including, most extensively, tryptophan. The possible use of such activities as 'markers' of agonal status in the selection of normal material and in the matching of control and pathological material in postmortem human brain studies is discussed.
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PMID:The influence of agonal status on some neurochemical activities of postmortem human brain tissue. 621 78

A boy with glutaric acidemia had psychomotor retardation first noted at age 6 months, recurrent metabolic acidosis, and a progressive quadriparesis with choreoathetosis. He died at age 3 1/2 years. Cultured skin fibroblasts lacked glutaryl-CoA dehydrogenase activity. There was a biochemical, but not a clinical, response to dietary restriction of lysine and tryptophan. The caudate and putamen of the brain showed severe loss of nerve cells and fibers with proliferation of astrocytes, as well as markedly reduced gamma-aminobutyric acid and glutamate decarboxylase activity.
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PMID:Glutaric acidemia: a metabolic disorder causing progressive choreoathetosis. 677 44

Irradiation of L-glutamate decarboxylase (L-glutamate 1-carboxy-lyase, EC 4.1.1.15) from Escherichia coli by visible light absorbed by the intrinsic chromophore, pyridoxal phosphate, caused the selective modification of two methionines per enzyme monomer. The disulfoxide derivative exhibited modified circular dichroism, chromatographic and kinetic properties, suggesting a conformational role for the two methionine residues. Irradiation of the enzyme in the presence of proflavin revealed the presence of two distinct groups of tryptophan residues with markedly different photooxidation rate constants. No evidence of involvement of tryptophans in the catalytic mechanisms of the enzyme was obtained. The results are compared with those obtained on irradiation of L-glutamate decarboxylase from Clostridium perfringens.
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PMID:Photo-oxidation of L-glutamate decarboxylase from Escherichia coli, sensitized by the coenzyme pyridoxal phosphate and by proflavin. 699 Sep 95

We previously provided what to our knowledge is the first evidence that plant glutamate decarboxylase (GAD) is a calmodulin (CaM)-binding protein. Here, we studied the GAD CaM-binding domain in detail. A synthetic peptide of 26 amino acids corresponding to this domain forms a stable complex with Ca2+/CaM with a 1:1 stoichiometry, and amino acid substitutions suggest that tryptophan-485 has an indispensable role in CaM binding. Chemical cross-linking revealed specific CaM/GAD interactions even in the absence of Ca2+. However, increasing KCI concentrations or deletion of two carboxy-terminal lysines abolished these interactions but had a mild effect on CaM/GAD interactions in the presence of Ca2+. We conclude that in the presence of Ca(2+)-hydrophobic interactions involving tryptophan-485 and electrostatic interactions involving the carboxy-terminal lysines mediate CaM/GAD complex formation. By contrast, in the absence of Ca2+, CaM/GAD interactions are essentially electrostatic and involve the carboxy-terminal lysines. In addition, a tryptophan residue and carboxy-terminal lysines are present in the CaM-binding domain of an Arabidopsis GAD. Finally, we demonstrate that petunia GAD activity is stimulated in vitro by Ca2+/CaM. Our study provides a molecular basis for Ca(2+)-dependent CaM/GAD interactions and suggests the possible occurrence of Ca(2+)-independent CaM/GAD interactions.
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PMID:Molecular and biochemical analysis of calmodulin interactions with the calmodulin-binding domain of plant glutamate decarboxylase. 761 Jan 59


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