Disease relevance of Glud1

• Therefore, during acidosis, the pH-responsive stabilization of GDH mRNA may be accomplished by the same mechanism that affects an increase in GA mRNA [1].
• Mitochondrial toxicity reflected itself also in decreased content of various cytochromes and reduced activity of enzymes, including glutamate dehydrogenase [2].
• Chronic ethanol consumption for 12 weeks (mean daily ethanol intake 11.4 gm per body weight corresponding to 29% of total energy intake) did not cause histological changes but decreased GPT activity, increased glutamate dehydrogenase and pyruvate kinase activities and did not alter their pp/pv distribution [3].
• Deficiencies of glial GDH and the consequent cytotoxic effects of high levels of excitatory amino acids may contribute to a number of neurodegenerative disorders [4].
• These mechanisms provide an explanation for hypoglycemia caused by mutations of GDH in children [5].

Psychiatry related information on Glud1

• The activities of alanine-, aspartate- and branched-chain amino-acid transaminases, glutamine synthetase, glutamate dehydrogenase and adenylate deaminase in white adipose tissue of adult male rats have been determined in animals submitted to 12-h cold exposure (4 degrees C) or to 24-h food deprivation [6].

High impact information on Glud1

• In isolated liver mitochondria, state 3 oxidation rates were unchanged or decreased, and activities of the mitochondrial enzymes, citrate synthetase, succinate dehydrogenase, carnitine palmitoyltransferase, and glutamate dehydrogenase (expressed per milligram mitochondrial protein) were unaffected by HCCL treatment [7].
• Serum glutamyl oxaloacetic transaminase and glutamate dehydrogenase activities were significantly increased in ethanol-fed rats [8].
• The leucine analog beta-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH) activates glutamate dehydrogenase [L-glutamate:NAD+ oxidoreductase (deaminating), EC 1.4.1.2] in pancreatic islet homogenates [9].
• The capacity of seven distinct amino acids to activate glutamate dehydrogenase tightly correlated with their ability to augment 14CO2 output from islets prelabeled with [U-14C]-glutamine and to stimulate insulin release in the presence of L-glutamine [9].
• Liver enzymes were detected in high amounts in the serum (eightfold elevation of glutamate dehydrogenase, fivefold elevation of alanine transaminase [ALT]) 7 hours after the first visible sign of apoptosis [10].

Chemical compound and disease context of Glud1

• The data indicate that glutamate dehydrogenase activity rather than glutamate transamination is primarily responsible for augmented ammoniagenesis in chronic acidosis [11].
• Experiments with [2-15N]glutamine or [15N]glutamate indicated that in chronic acidosis approximately 30% of ammonia nitrogen was derived either from 2-N of glutamine or glutamate-N by the activity of glutamate dehydrogenase [11].
• Regulation and differential expression of gdhA encoding NADP-specific glutamate dehydrogenase in Neisseria meningitidis clinical isolates [12].
• 5. The decrease in 2-oxoglutarate concentration seen in acute acidosis implies a fall in intramitochondrial pH in kidney, and is the result of two phenomena, accelerated disposal via 2-oxoglutarate dehydrogenase and maintenance of near equilibrium of glutamate dehydrogenase [13].
• Vitamin B-6 deficiency led to the expected decreases in the activities of hepatic alanine and aspartate aminotransferases but did not influence those of glutamate dehydrogenase (EC 1.4.1.2), pyruvate carboxylase (EC 6.6.1.1), phosphoenolpyruvate carboxykinase (EC 4.1.1.32) and pyruvate kinase (EC 2.7.1.40) [14].

Biological context of Glud1

• Nucleotide sequence of rat liver glutamate dehydrogenase cDNA [15].
• The 52 kDa protein was identified as mitochondrial glutamate dehydrogenase (EC 1.4.1.3) by amino acid sequence analysis [16].
• Identification and analysis of a matrix-attachment region 5' of the rat glutamate-dehydrogenase-encoding gene [17].
• We here report identification, mapping and sequencing of an (A + T)-rich MAR located 2010-1397 bp upstream of the transcription initiation site of GDH, that mediates strong binding to the nuclear matrix [17].
• The GDH MAR, and MAR-containing fragments derived from other species, were found to bind to the same binding sites in the nuclear matrix, although the affinity varied [17].

Anatomical context of Glud1

• Regional distribution of astrocytes with intense immunoreactivity for glutamate dehydrogenase in rat brain: implications for neuron-glia interactions in glutamate transmission [4].
• The principally mitochondrial enzyme glutamate dehydrogenase (GDH) exhibited low-intensity, uniform immunoreactivity in neurons and intense heterogeneous labeling of glial cells of rat brain [4].
• Activities of mitochondrial enzymes expressed per area of mitochondrial membrane or per mitochondrial volume were either unchanged (ATPase, cytochrome c oxidase and glutamate dehydrogenase) or decreased (monoamine oxidase) in bile duct ligation [18].
• However, the central gray of the midbrain, the nuclei of the reticular formation, brain stem regions projecting to the cerebellum, and cranial nuclei of the trigeminal and vagal nerves also exhibited intense glial labeling for GDH, even though some of these regions are known to receive only weak glutamatergic projections [4].
• Glutamate dehydrogenase activation and ammonia formation by rat kidney mitochondria [19].

Associations of Glud1 with chemical compounds

• Identification of the CoA-modified forms of mitochondrial acetyl-CoA acetyltransferase and of glutamate dehydrogenase as nearest-neighbour proteins [16].
• The results of co-immunoprecipitation and cross-linking characterize the CoA-modified forms of acetyl-CoA acetyltransferase and the glutamate dehydrogenase as nearest-neighbour proteins [16].
• A mechanism of sulfite neurotoxicity: direct inhibition of glutamate dehydrogenase [20].
• Because glutamate is a major metabolite in the brain, inhibition of GDH by sulfite could contribute to the severe phenotype of sulfite oxidase deficiency in human infants [20].
• The activation of glutamate dehydrogenase by BCH may thus account for the insulin-releasing capacity of the leucine analog [9].

Physical interactions of Glud1

• RNA EMSAs established that zeta-crystallin also binds to the full-length 3'-UTR of GDH mRNA [1].

Regulatory relationships of Glud1

• The specific activity of pyruvate carboxylase in non-parenchymal cells expressed as the percentage of that in parenchymal cells was onlu 2% for glutamate dehydrogenase 4.3% and for cytochrome c oxidase 79.4% [21].
• Histochemical demonstration of glutamate dehydrogenase and phosphate-activated glutaminase activities in semithin sections of the rat retina [22].

Other interactions of Glud1

• Liver glutamine synthase activity increased by 58% and glutamate dehydrogenase by 40%, whereas glutaminase was not affected [23].
• To eliminate the potential interference of the long half-lives of some of these proteins on the interpretation of the results, we also studied the distribution of the mRNAs of carbamoylphosphate synthase, glutamine synthase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase [24].
• To analyze the effect of galactose, male Wistar rats were pretreated with lactulose (Duphalac, 9.1 gm per kg per day) and given Gal-N (375 mg per kg i.p.). After 24 hr, serum was analyzed for glutamic pyruvate transaminase, glutamate dehydrogenase, and sorbitol dehydrogenase activities [25].
• After swelling in an isotonic solution of permeant ions, N-butylmaleimide-treated mitochondrial lost one-half of their malate dehydrogenase content, whereas fumarase and glutamate dehydrogenase did not leave the matrix space [26].
• Total skeletal muscle alanine, aspartate, and branched chain aminotransferase, glutamate dehydrogenase, and malic enzyme activities were not significantly altered in any treatment groups [27].

Analytical, diagnostic and therapeutic context of Glud1

• Two of the original 10 candidate genes implicated by RNA fingerprinting, the rat homolog of the ryanodine receptor type-2 and glutamate dehydrogenase (EC 1.4.1.3), were further investigated by Northern blot analysis, reverse transcription-PCR, and in situ hybridization and confirmed as MRGs with distinct temporal and regional expression [28].
• The in vivo activity of glutamate dehydrogenase (GDH) in the direction of reductive amination was measured in rat brain at steady-state concentrations of brain ammonia and glutamate after intravenous infusion of the substrate 15NH4+ [29].
• Moreover, beadlets resulted in proliferation of the smooth endoplasmic reticulum and in leakage of the mitochondrial glutamate dehydrogenase into the plasma, reflecting mitochondrial injury (both documented by electron microscopy) [30].
• The turnover of GDH appeared to be unaffected by thyroidectomy [31].
• Further evidence that the antibodies were selective for glutamate dehydrogenase in rat cerebellum was obtained through peptide mapping [32].

References