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)

Channel catfish (Ictalurus punctatus) were exposed, in situ, to sewage effluent for 17 days to determine the effect of unionized ammonia (UIA) on concentrations of glutamate, glutamine and alpha-ketoglutarate (alpha-KGA) in brain tissue, and activity of glutamate dehydrogenase (L-GDH) in liver tissue. Fish were held in cages either 600 m upstream (0.005 +/- 0.001 mg/liter as UIA, means +/- SE, n = 6) or 9 km downstream (0.032 +/- 0.004 mg/liter, means +/- SE, n = 6). The mean concentrations in micromoles per gram wet weight (means +/- SE, n = 27-30) for glutamate, glutamine, and alpha-KGA at the upstream location were 3.04 +/- 0.29, 5.76 +/- 0.29, and 0.003 +/- 0.01, respectively. Mean concentrations in micromoles per gram wet weight (means +/- SE, n = 27-30) for glutamate, glutamine, and alpha-KGA at the downstream location were 3.03 +/- 0.29, 4.60 +/- 0.37, and 0.02 +/- 0.004, respectively. Mean L-GDH activity in units per milligram protein (means +/- SE, n = 28-30) at the upstream and downstream locations were 0.095 +/- 0.003 and 0.092 +/- 0.003, respectively. Neither the concentrations of these three brain tissue substrates, nor L-GDH activity were significantly different between fish at the two locations even though the observed UIA concentrations were equivalent to concentrations which have been observed to increase glutamine concentration in brain tissue of catfish during exposures under laboratory conditions. Therefore, under the observed field conditions these parameters were not useful biochemical indicators of exposure to potentially detrimental concentrations of UIA.
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PMID:Sewage effluent biomonitoring. II. Biochemical indicators of ammonia exposure in channel catfish. 286 28

The release of GA (mitochondrial glutaminase) from neurons following acute ischaemia or during chronic neurodegenerative diseases may contribute to the propagation of glutamate excitotoxicity. Thus an inhibitor that selectively inactivates the released GA may limit the accumulation of excess glutamate and minimize the loss of neurological function that accompanies brain injury. The present study examines the mechanism of inactivation of rat KGA (kidney GA isoform) by the small-molecule inhibitor BPTES [bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide]. BPTES is a potent inhibitor of KGA, but not of the liver GA isoform, glutamate dehydrogenase or gamma-glutamyl transpeptidase. Kinetic studies indicate that, with respect to glutamine, BPTES has a K(i) of approx. 3 microM. Moreover, these studies suggest that BPTES inhibits the allosteric activation caused by phosphate binding and promotes the formation of an inactive complex. Gel-filtration chromatography and sedimentation-velocity analysis were used to examine the effect of BPTES on the phosphate-dependent oligomerization of KGA. This established that BPTES prevents the formation of large phosphate-induced oligomers and instead promotes the formation of a single oligomeric species with distinct physical properties. Sedimentation-equilibrium studies determined that the oligomer produced by BPTES is a stable tetramer. Taken together, the present work indicates that BPTES is a unique and potent inhibitor of rat KGA and elucidates a novel mechanism of inactivation.
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PMID:Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). 1758 Nov 13

Glutaminase (KGA/isoenzyme GAC) is an emerging and important drug target for cancer. Traditional methods for assaying glutaminase activity are coupled with several other enzymes. Such coupled assays do not permit the direct and stringent characterization of specific glutaminase inhibitors. Ebselen was identified as a potent 9 nM KGA inhibitor in the KGA/glutamate oxidase (GO)/horse radish peroxidase (HRP) coupled assay but showed very weak activity in inhibiting the growth of glutamine-dependent cancer cells. For rigorous characterization, we developed a direct kinetic binding assay for KGA using bio-layer interferometry (BLI) as the detection method; Ebselen was identified as a GDH inhibitor but not a KGA inhibitor. Furthermore, we designed and synthesized several benzo[d][1,2]selenazol-3(2H)-one dimers which were subjected to SAR analysis by several glutaminolysis specific biochemical and cell based assays. Novel glutamate dehydrogenase (GDH) or dual KGA/GDH inhibitors were discovered from the synthetic compounds; the dual inhibitors completely disrupt mitochondrial function and demonstrate potent anticancer activity with a minimum level of toxicity.
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PMID:Biomolecular Interaction Assays Identified Dual Inhibitors of Glutaminase and Glutamate Dehydrogenase That Disrupt Mitochondrial Function and Prevent Growth of Cancer Cells. 2820 1