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)

Glutamate decarboxylase, gamma-aminobutyrate-alpha-ketoglutarate aminotransferase and NAD-linked and NADP-linked succinic semialdehyde dehydrogenase, all constituting the GABA (gamma-aminobutyrate)-shunt pathway of glutamate metabolism are localized in the mitochondrial matrix in a streptomycin-bleached mutant of Euglena gracilis strain Z. Glutamate dehydrogenase, requiring NADP as the cofactor, was distributed in the cytoplasm. An improved version of the controlled digestion method for preparing Euglena mitochondria, which involves use of trypsin and a trypsin inhibitor and removal of broken cells before mechanical disruption of cells, is also described.
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PMID:Subcellular localization of the GABA-shunt enzymes in Euglena gracilis strain Z. 11 50

The activity of glutamate dehydrogenase (EC 1.41.1.3) is studied in homogenates and subcellular fractions of five limbic structures: regio superior, regio inferior of hippocampus, fascia dentata, septum and corpora mamillaria. The lowest activity of the enzyme is found in regio superior of hippocampus. 80% of the total enzyme activity of primary fractions is found in "crude" mitochondria. After centrifugation of the latter within the linear sucrose density gradient the distribution of the enzume activity is similar for different structures and the highest activity is found in the region of sucrose molarity from 1.44 up to 1.50 M which corresponds to the mitochondria distribution region. 50% of the total found activity is in the fraction enriched by mitochondria, 30% is in the fraction enriched by nerve endings with the high activity of glutamate decarboxylase. It was found for different fractions that 1 mM of ADF with 0.2 mM NAD-H+ produces about 10-fold increase in the enzyme activity. Pyridoxal-5'-phosphate inhibits the enzyme from inactivation. The results are discussed in connection with the possible role of pyridoxal-5'-phosphate in regulation of the glutamate dehydrogenase activity in vivo.
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PMID:[Glutamate dehydrogenase activity in the structures of the rabbit brain limbic system]. 82 51

ADVERSE EFFECTS OF OXYGEN: Adverse effect of oxygen on anaerobes implies oxidation of the basic cell constituents NAD(P)H, thiols, iron-sulphur proteins, pteridines and others) and inactivation of the essential components of the active site of enzymes. Oxygen can also adversely affect the aerobes, especially if long-term influence is taken into consideration, while exposition to high-pressure oxygen causes considerable damages. Direct influence of oxygen on aerobes due to slow and limited enzyme inactivation (for example glutamate decarboxylase) and small number of affected "targets" is not responsible for total adverse effects of oxygen. Even in 1954 it was supposed that oxygen free radicals are the most responsible for the adverse effects of oxygen. ATMOSPHERIC (TRIPLET) OXYGEN: Electron configuration of triplet oxygen explains its reactivity since it is a biradical. The reactions of oxygen with non-radicals are possible with participation of transition metals (except zinc), while its reactivity is much more expressed in case of reactions with other radical species. ACTIVE OXYGEN: More reactive forms of oxygen, known as singlet oxygen, can be generated by an input of energy to triplet oxygen. Singlet-oxygen is obtained mainly by photoexcitation in the presence of initiators (methylene blue, chlorophyll etc.) and as a product of reactions of ozone with certain biomolecules. REDUCED FORMS OF OXYGEN: If a single electron is added to the triplet oxygen, it must enter one of the antibonding molecular orbitals and produce the superoxide radical--(O2.-). Addition of one more electron produces peroxide ion--O2(2-), which forms hydro peroxide in presence of H+, the most common two-electron reduction product of oxygen in biological systems. The four-reduction product of oxygen in biological systems is water. SUPEROXIDE RADICAL: The in vivo production of superoxide radical is possible in many different ways mentioned in this paper. This radical species is unstable in water solutions because of dismutation reaction leading to non-enzymic generation of hydroperoxide. The most reactive radical species--hydroxyl radical is produced from hydro peroxide by Fenton or Haber-Weiss reactions in the presence of catalytic transition metals (iron or copper). HYDROXYL RADICAL: Hydroxyl radicals are the most reactive radical species. The way of their generation has been shown in detail in this paper with special emphasis given to Fenton and Haber-Weiss reactions, that is, transition metals (iron and copper) as catalizators for these reactions. The reactivity of hydroxyl radical can be recognized by monitoring the second-order rate constants for reactions of the hydroxyl radical with some organic compounds in aqueous solution presented in this paper. Although the number of compounds that can be affected and damaged by hydroxyl radicals is great, until now, attention has been paid mostly to investigation of attacks of these radical species on lipids, proteins and DNA. LIPID PEROXIDATION: Radicals react with lipids and cause oxidative destruction of unsaturated, that is, polyunsaturated fatty acids, known as lipid peroxidation. Both lipids in biological systems and lipids as food constituents are submitted to this process. Lipid peroxidation is a chain reaction and its mechanism has been shown in detail in this paper. Lipid peroxidation in cells leads to direct damage of cell membranes with indirect damages of other cell constituents, caused by reactivity of secondary products of this reaction, aldehydes. This complex reaction is responsible for damages of many tissues and progress of some diseases (atherosclerosis). OXIDATIVE STRESS: Protection of an organism from oxygen free radicals implies activity of enzymatic (catalase, SOD, glutathione peroxidase, glutathione reductase etc.) and nonenzymatic (vitamin E. vitamin C. glutathione, uric acid etc.) systems of protection. Disturbance of the balance between production of oxygen free radicals (or some other radical species) and activity of antioxidative system of protection causes the so called oxidative stress. An organism can tolerate a mild oxidative stress but a higher disturbance between the production of free radicals and the activity of the antioxidative protection results in lipid protein and DNA as well as numerous diseases.
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PMID:[Free oxygen radiacals and kidney diseases--part I]. 1132 Jul 27

Labeled glutamate was rapidly converted to gamma-aminobutyrate in intact, excised radish (Raphanus sativus L., var. Champion) leaves. Labeled gamma-aminobutyrate was metabolized via succinate and the Krebs cycle and was not carboxylated to form glutamate. Administration of carbon-14 and tritium-labeled succinate indicated that less than 10% of the gamma-aminobutyrate formation occurs by amination of succinic semialdehyde. Therefore, most gamma-aminobutyrate formation must be via glutamate decarboxylation.Radish leaf extracts were more active in catalyzing transamination between gamma-aminobutyrate and pyruvate than that between gamma-aminobutyrate and alpha-ketoglutarate. Glutamate decarboxylase was approximately 20 times more active than gamma-aminobutyrate: pyruvate transaminase. Succinic semialdehyde dehydrogenase was found in the extracts, and NAD was much more active as a hydrogen acceptor than NADP. No reduction of succinate to succinic semialdehyde by the NAD-linked dehydrogenase could be demonstrated. The following pH optima were determined: glutamate decarboxylase, 5.9; gamma-aminobutyrate: pyruvate transaminase, 8.9; succinic semialdehyde: NAD dehydrogenase, about 9.0.
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PMID:In Vivo and In Vitro Studies on gamma-Aminobutyric Acid Metabolism with the Radish Plant (Raphanus sativus, L.). 1665 5

An elicitor derived from the cell wall of rice blast fungus (Magnaporthe grisea) causes cell death in suspension cultured cells of rice (Oryza sativa L.). To elucidate the role of M. grisea elicitor on metabolic pathway of rice cells, we performed metabolite profiling using capillary electrophoresis-mass spectrometry (CE/MS). Treatment with M. grisea elicitor increased the amounts of antioxidants and free amino acids and decreased the amount of metabolites in the tricarboxylic acid (TCA) cycle. Lower ATP concentration caused aberrant energy charge, concurrently with reduced amount of NAD(P)H in elicitor treated cells. Among free amino acids detected in this study, the level of gamma-aminobutyric acid (GABA) increased. GABA is metabolized through a bypass pathway of the TCA cycle called GABA shunt, which is composed of glutamate decarboxylase (GAD), GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). While M. grisea elicitor negligibly affected GAD and SSADH, GABA-T activity significantly decreased. The decrease in GABA-T activity was recovered by NADPH oxidase inhibitor, which prevents cell death induced by M. grisea elicitor. Thus, GABA accumulation observed in rice cells under elicitor stress is partly associated with GABA-T activity.
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PMID:The cell death factor, cell wall elicitor of rice blast fungus (Magnaporthe grisea) causes metabolic alterations including GABA shunt in rice cultured cells. 1951 97

Sobue and Nakajima (1978) reported that GABA formation from putrescine is significant in chick embryo brain between days 6 and 8 of incubation. They attributed an important functional role to the putrescine-derived GABA. We found that depletion of putrescine and spermidine in chick embryos by inhibition of ornithine decarboxylase activity did not decrease the in vivo rate of GABA formation, showing that putrescine is, from a quantitative point of view, a negligible source for GABA in chick embryo brain. The changes of brain GABA levels obtained after administration of glutamate decarboxylase inhibitors and in vitro determinations of glutamate decarboxylase activity were compatible with the assumption that GABA is mainly formed by decarboxylation of l-glutamate, even during early brain development. Participation of the NAD(+)-dependent, aerobic transformation of glutamate into GABA (Seiler and Wagner, 1976) in the overall GABA production of chick embryo brain could, however, not be excluded.
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PMID:Metabolic routes of GABA formation in chick embryo brain. 2048 91

Glutamate synthase (E.C. 1.4.1.14) (GOGAT) activity was not detectable in L3 Haemonchus contortus, but was present in L3 Teladorsagia circumcincta and adult worms of both species. GOGAT activity was inhibited by 80% by azaserine. Activity (nmol min(-1) mg(-1) protein) was 33-59 in adult H. contortus, 51-91 in adult T. circumcincta and 24-41 in L3 T. circumcincta, probably depending on exposure to ammonia, as incubation with 1mM NH(4)Cl doubled GOGAT activity. The pH optimum was 7.5 in both species. Either NAD or NADP acted as co-factor. The mean apparent K(m) for 2-oxoglutarate was 0.7 (0.5-0.9) mM and for glutamine was 1.0 (0.5-1.7) mM for different homogenates. There was no detectable activity in whole parasite homogenates of glutamate decarboxylase (E.C. 4.1.1.15) or succinic semialdehyde dehydrogenase (E.C. 1.2.1.24), the first and third enzymes of the GABA shunt, respectively, suggesting that the GABA shunt is not important in general metabolism in these species.
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PMID:Glutamate synthase, but not GABA shunt enzymes, contributes to nitrogen metabolism of the sheep abomasal nematode parasites Haemonchus contortus and Teladorsagia circumcincta. 2057 19