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:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Islets were isolated by automatic digestion from non-diabetic cadaveric organ donors and from Type 2 (non-insulin-dependent) diabetic subjects. The activity of FAD-glycerophosphate dehydrogenase, but not that of either glutamate dehydrogenase, glutamate-oxalacetate transaminase or glutamate-pyruvate transaminase, was lower in Type 2 diabetic patients than control subjects. Hexokinase, glucokinase and glutamate decarboxylase activities were also measured in islets from control subjects. The utilization of D-[5-3H]glucose, oxidation of D-[6-14C]glucose and release of insulin evoked by D-glucose were all lower in Type 2 diabetic patients than control subjects. The secretory response to the combination of L-leucine and L-glutamine appeared less severely affected. Islets from Type 2 diabetic patients may thus display enzymatic, metabolic and secretory anomalies similar to those often observed in animal models of Type 2 diabetes, including a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle.
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PMID:Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients. 816 52

Rat pancreatic beta cells exhibit a 16-fold higher glutamate decarboxylase (GAD) activity than islet non-beta cells, but a similar glutamate dehydrogenase (GDH) activity. beta Cells which survive exposure to 2 mM streptozotocin only contain 10 percent of the GAD activity of control cells, but their GDH activity remains unaltered. Culture of streptozotocin-treated beta cell preparations with 2 mM nicotinamide reduces the number of dead cells and prevents in part the decline in GAD activity of surviving beta cells. These data indicate that loss in activity of the beta cell specific enzyme GAD can serve as marker for beta cells which survived a destructive process. It is furthermore demonstrated that nicotinamide increases the percent surviving cells and decreases their loss in GAD activity.
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PMID:Reduced glutamate decarboxylase activity in rat islet beta cells which survived streptozotocin-induced cytotoxicity. 840 62

In islets from adult rats injected with streptozotocin during the neonatal period, both a nonmetabolized analog of L-leucine and 3-phenylpyruvate augmented 14CO2 output from islets either prelabeled with L-[U-14C]glutamine or exposed to D-[2-14C]glucose and D-[6-14C]glucose, in a manner qualitatively comparable to that found in islets from control rats. The islets of diabetic rats differed, however, from those of control rats by their unresponsiveness to both the L-leucine analog and a high concentration of D-glucose in terms of increasing 3HOH generation from [2-3H]glycerol, an impaired sparing action of the hexose upon 14CO2 output from islets prelabeled with [U-14C]palmitate, and, most importantly, by a decreased rate of D-[2-14C]glucose and D-[6-14C]glucose oxidation when either incubated at a high concentration of the hexose (16.7 mM) or stimulated by nonglucidic nutrient secretagogues at a low concentration of D-glucose (2.8 mM). In islet homogenates, the activity of glyceraldehyde phosphate dehydrogenase, glutamate decarboxylase, and NADP-malate dehydrogenase was lower in diabetic than control islets. Such was not the case for glutamate-alanine transaminase, glutamate-aspartate transaminase, or glutamate dehydrogenase. The neonatal injection of streptozotocin thus affected, in the adult rats, the activity of several islet enzymes. Nevertheless, the metabolic data suggest that an impaired circulation in the glycerol phosphate shuttle, as observed in response to stimulation of the islets by either a high concentration of D-glucose or nonglucidic nutrient secretagogues, represents an essential determinant of the preferential impairment of glucose-induced insulin release in this model of non-insulin-dependent diabetes.
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PMID:Metabolic response to nonglucidic nutrient secretagogues and enzymatic activities in pancreatic islets of adult rats after neonatal streptozotocin administration. 848 60

In type I (insulin-dependent) diabetes, destruction of pancreatic beta cells has been associated with the presence of circulating antibodies against glutamate decarboxylase (GAD), a GABA (gamma-aminobutyric acid) synthesizing enzyme which is located in the beta cells. We examined whether destruction of islet beta cells can lead to discharge of GAD in the extracellular medium, making it a potential autoantigen. Rat islet beta cells were first exposed for 1 hour to streptozotocin and then cultured for 4 to 24 hours before cellular and medium GAD activities were measured. After 24 hours culture, 70 percent of streptozotocin-treated beta cells were disintegrated whereas the number of control cells remained unchanged. Control cells exhibited a stable cellular GAD activity over the 24 hour period with no enzyme activity detectable in their culture medium. The cells recovered 24 hours after streptozotocin treatment exhibited 10-fold lower levels of GAD-activity and of GABA; their culture medium contained GAD, its enzymatic activity reaching peak values after 10 hours. The beta-cell enzymes glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase were not detectable in the medium of control or streptozotocin-treated cells. Similar observations were made when beta cells had been exposed to cytotoxic concentrations of alloxan. It is concluded that damage to rat islet beta cells results in transient discharge of GAD in the extracellular medium making this enzyme a candidate extracellular marker for beta cell toxic processes and a potential autoantigen for immune reactivity.
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PMID:Damaged rat beta cells discharge glutamate decarboxylase in the extracellular medium. 892 Sep 8

Ornithine decarboxylase (ODC) from Lactobacillus 30a catalyses the cleavage of alpha-methylornithine into ammonia and 2-methyl-1-pyrroline; glutamate decarboxylase (GAD) from Escherichia coli catalyses the cleavage of alpha-methylglutamate into ammonia and laevulinic acid. In our analyses, 2-methyl-1-pyrroline and laevulinic acid were identified by HPLC and mass spectroscopic analysis, and ammonia was identified by means of glutamate dehydrogenase. Molecular oxygen was consumed during these reactions in a 1:2 molar ratio with respect to the products. The catalytic efficiencies (k(cat)/K(m)) of the reactions catalysed by ODC and GAD were determined as 12500 and 9163 M(-1).min(-1) respectively. When the reactions were performed under anaerobic conditions, no ammonia, 2-methyl-1-pyrroline or laevulinic acid was produced to a significant extent. The formation of ammonia and O(2) consumption (in a 1:2 molar ratio with respect to ammonia) were also detected during the reaction of ODC and GAD with putrescine and gamma-aminobutyrate respectively. Taken together, these findings clearly indicate that ODC and GAD catalyse an oxidative deamination of their decarboxylation products, a reaction similar to that catalysed by dopa decarboxylase (DDC) with alpha-methyldopa [Bertoldi, Dominici, Moore, Maras and Borri Voltattorni (1998) Biochemistry 37, 6552-6561]. Furthermore, this reaction was accompanied by a decarboxylation-dependent transamination occurring for GAD, DDC and ODC with a frequency of approx. 0.24%, 1% and 9% respectively compared with that of oxidative deamination.
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PMID:Ornithine and glutamate decarboxylases catalyse an oxidative deamination of their alpha-methyl substrates. 1047 60

Studies of neuroactive amino acids and their regulatory enzymes in surgically excised focally epileptic human brain are reviewed. Concentrations of glutamate, aspartate and glycine are significantly increased in epileptogenic cerebral cortex. The activities of the enzymes, glutamate dehydrogenase and aspartate aminotransferase, involved in glutamate and aspartate metabolism are also increased. Polyamine synthesis is enhanced in epileptogenic cortex and may contribute to the activation of N-methyl-D-aspartate (NMDA) receptors. Nuclear magnetic resonance spectroscopy (NMRS) reveals that patients with poorly controlled complex partial seizures have a significant diminution in occipital lobe gamma aminobutyric acid (GABA) concentration. The activity of the enzyme GABA-aminotransaminase (GABA-T) which catalyzes GABA degradation is not altered in epileptogenic cortex. NMRS studies show that vigabatrin, a GABA-T inhibitor and effective antiepileptic, significantly increases brain GABA. Glutamate decarboxylase (GAD), responsible for GABA synthesis, is diminished in interneurons in discrete regions of epileptogenic cortex and hippocampus. In vivo microdialysis performed in epilepsy surgery patients provides measurements of extracellular amino acid levels during spontaneous seizures. Glutamate concentrations are higher in epileptic hippocampi and increase before seizure onset reaching potentially excitotoxic levels. Frontal or temporal cortical epileptogenic foci also release aspartate, glutamate and serine particularly during intense seizures or status epilepticus. GABA in contrast, exhibits a delayed and feeble rise in the epileptic hippocampus possibly due to a reduction in the number and/or efficiency of GABA transporters.
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PMID:Neuroactive amino acids in focally epileptic human brain: a review. 1055 79

GABAergic and glutamatergic neuronal systems in adult normal human brains were shown quantitatively and in detail through the distributions of glutamate decarboxylase (GAD) and glutamate dehydrogenase (GDH), respectively. Consecutive coronal sections containing part of the striatum and the substantia nigra were obtained from the right hemisphere of three deceased persons with no history of neurological or psychiatric diseases and were stained immunohistochemically for GAD and GDH. Each stained section was divided into approximately 3 million microareas and the immunohistochemical fluorescence intensity in each area was measured by a human brain mapping analyzer, which is a microphotometry system for analysis of the distribution of neurochemicals in a large tissue slice. In the analyzed brain regions, conspicuously intense GAD-like immunoreactivity was observed in the substantia nigra, globus pallidus, and hypothalamus. GDH was widely and rather evenly distributed in the gray matter compared to GAD, although intense GDH-like immunoreactivity was observed in the lateral geniculate nucleus and substantia nigra. Within the substantia nigra, the globus pallidus, and other regions, characteristic distributions of GAD- and GDH-like immunoreactivity were found. We believe that the analysis of the human brain by this novel technique can help to understand the functional distribution of neuronal systems in the normal human brain and may be able to identify abnormal changes in the diseased human brain. It can also provide basic data to help in the interpretation of functional magnetic resonance imaging or positron emission tomography.
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PMID:Quantitative maps of GAbAergic and glutamatergic neuronal systems in the human brain. 1106 36

There is strong evidence for the involvement of the neurotransmitter glutamate system in the pathogenesis of Alzheimer's disease and schizophrenia. In these mental diseases, the brain shows changes in the levels of glutamate and in the function and expression of its transporters and receptors. Since the levels of glutamate are largely determined by the rate of its metabolism, the changes of its concentrations may be associated with dysfunctions of appropriate enzymes. Actually, disturbances of glutamate metabolic enzymes, such as glutaminase, glutamate decarboxylase, and glutamine synthetase were detected in the brain of patients with Alzheimer's disease. The alterations in the expression of glutamine synthetase, glutamine synthetase-like protein, and three isoenzymes of glutamate dehydrogenase in the frontal cortex of patients with schizophrenia suggest that there are impaired glutamate metabolism in this mental disease and Alzheimer's disease.
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PMID:[Impaired cerebral glutamate metabolism in mental diseases (Alzheimer's disease, schizophrenia]. 1152 27

The fractionation of the venom of Indian red scorpion (Mesobuthus tamulus) was performed using CM-52 (carboxy methyl cellulose) ion-exchange chromatography. The toxic potential of these fractions were tested on lepidoptera larvae and mice. The CM-52 fractions, which showed toxicity were further used to study their impact on glutamate metabolism. The glutamate content increased and glutamine synthetase and glutamate decarboxylase activity levels were elevated in envenomated animals. The present results reveal that glutamine is rapidly metabolized to glutamate and gamma-aminiobutyric acid indicating that the pool of neurotransmitters is maintained and regulated by glutamine biosynthesis. The scorpion neurotoxins inhibit the glutamate dehydrogenase activity, suggesting a decreased deamination of glutamate.
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PMID:Fractionation of scorpion (Mesobuthus tamulus) venom and the impact of specific fractions on glutamate metabolism. 1218 50

We have carried out a detailed examination of L-glutamine metabolism in rat islets in order to elucidate the paradoxical failure of L-glutamine to stimulate insulin secretion. L-Glutamine was converted by isolated islets into GABA (gamma-aminobutyric acid), L-aspartate and L-glutamate. Saturation of the intracellular concentrations of all of these amino acids occurred at approx. 10 mmol/l L-glutamine, and their half-maximal values were attained at progressively increasing concentrations of L-glutamine (0.3 mmol/l for GABA; 0.5 and 1.0 mmol/l for Asp and Glu respectively). GABA accumulation accounted for most of the 14CO2 produced at various L-[U-14C]glutamine concentrations. Potentiation by L-glutamine of L-leucine-induced insulin secretion in perifused islets was suppressed by malonic acid dimethyl ester, was accompanied by a significant decrease in islet GABA accumulation, and was not modified in the presence of GABA receptor antagonists [50 micromol/l saclofen or 10 micromol/l (+)-bicuculline]. L-Leucine activated islet glutamate dehydrogenase activity, but had no effect on either glutamate decarboxylase or GABA transaminase activity, in islet homogenates. We conclude that (i) L-glutamine is metabolized preferentially to GABA and L-aspartate, which accumulate in islets, thus preventing its complete oxidation in the Krebs cycle, which accounts for its failure to stimulate insulin secretion; (ii) potentiation by L-glutamine of L-leucine-induced insulin secretion involves increased metabolism of L-glutamate and GABA via the Krebs cycle (glutamate dehydrogenase activation) and the GABA shunt (2-oxoglutarate availability for GABA transaminase) respectively, and (iii) islet release of GABA does not seem to play an important role in the modulation of the islet secretory response to the combination of L-leucine and L-glutamine.
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PMID:Conversion into GABA (gamma-aminobutyric acid) may reduce the capacity of L-glutamine as an insulin secretagogue. 1476


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