Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthesis of wild-type Neurospora crassa assimilatory nitrate reductase is induced in the presence of nitrate ions and repressed in the presence of ammonium ions. Effects of several Neurospora mutations on the regulation of this enzyme are shown: (i) the mutants, nit-1 and nit-3, involving separate lesions, lack reduced nicotinamide adenine dinucleotide (NADPH)-nitrate reductase activity and at least one of three other activities associated with the wild-type enzyme. The two mutants do not require the presence of nitrate for induction of their aberrant nitrate reductases and are constitutive for their component nitrate reductase activities in the absence of ammonium ions. (ii) An analog of the wild-type enzyme (similar to the nit-1 enzyme) is formed when wild type is grown in a medium in which molybdenum has been replaced by vanadium or tungsten; the resulting enzyme lacks NADPH-nitrate reductase activity. Unlike nit-1, wild type produced this analog only in the presence of nitrate. Contaminating nitrate does not appear to be responsible for the observed mutants' activities. Nitrate reductase is proposed to be autoregulated. (iii) Mutants (am) lacking NADPH-dependent glutamate dehydrogenase activity partially escape ammonium repression of nitrate reductase. The presence of nitrate is required for the enzyme's induction. (iv) A double mutant, nit-1 am-2, proved to be an ideal test system to study the repressive effects of nitrogen-containing metabolites on the induction of nitrate reductase activity. The double mutant does not require nitrate for induction of nitrate reductase, and synthesis of the enzyme is not repressed by the presence of high concentrations of ammonium ions. It is, however, repressed by the presence of any one of six amino acids. Nitrogen metabolites (other than ammonium) appear to be responsible for the mediation of "ammonium repression."
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PMID:Induction and repression of nitrate reductase in Neurospora crassa. 14

Hyperthermophiles are a recently discovered group of microorganisms that grow at and above 90 degrees C. They currently comprise over 20 different genera, and except for two novel bacteria, all are classified as Archaea. The majority of these organisms are obligately anaerobic heterotrophs that reduce elemental sulfur (S degree) to H2S. The best studied from a biochemical perspective are the archaeon, Pyrococcus furiosus, and the bacterium, Thermotoga maritima, both of which are saccharolytic. P. furiosus is thought to contain a new type of Entner-Doudoroff pathway for the conversion of carbohydrates ultimately to acetate, H2 and CO2. The pathway is independent of nicotinamide nucleotides and involves novel types of ferredoxin-linked oxidoreductases, one of which has tungsten, a rarely used element, as a prosthetic group. The only site of energy conservation is at the level of acetyl CoA, which is the presence of ADP and phosphate is converted to acetate and ATP in a single step. In contrast, T. maritima utilizes a conventional Embden-Meyerhof pathway for sugar oxidation. P. furiosus also utilizes peptides as a sole carbon and energy source. Amino acid oxidation is thought to involve glutamate dehydrogenase together with at least three types of novel ferredoxin-linked oxidoreductases which catalyze the oxidation of 2-ketoglutarate, aryl pyruvates and formaldehyde. One of these enzymes also utilizes tungsten. In P. furiosus, virtually all of the reductant that is generated during the catabolism of both carbohydrates and peptides is channeled to a cytoplasmic hydrogenase. This enzyme is now termed sulhydrogenase, as it reduces both protons to H2 and S degrees (or polysulfide) to H2S. S degrees reduction appears to lead to the conservation of energy in P. furiosus but not in T. maritima, although the mechanism by which this occurs is not known.
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PMID:Biochemical diversity among sulfur-dependent, hyperthermophilic microorganisms. 794 71

Patients affected by sulfite oxidase (SO) deficiency present severe seizures early in infancy and progressive neurological damage, as well as tissue accumulation of sulfite, thiosulfate and S-sulfocysteine. Since the pathomechanisms involved in the neuropathology of SO deficiency are still poorly established, we evaluated the effects of sulfite on redox homeostasis and bioenergetics in cerebral cortex, striatum, cerebellum and hippocampus of rats with chemically induced SO deficiency. The deficiency was induced in 21-day-old rats by adding 200ppm of tungsten, a molybdenum competitor, in their drinking water for 9weeks. Sulfite (70mg/kg/day) was also administered through the drinking water from the third week of tungsten supplementation until the end of the treatment. Sulfite decreased reduced glutathione concentrations and the activities of glutathione reductase and glutathione S-transferase (GST) in cerebral cortex and of GST in cerebellum of SO-deficient rats. Moreover, sulfite increased the activities of complexes II and II-III in striatum and of complex II in hippocampus, but reduced the activity of complex IV in striatum of SO-deficient rats. Sulfite also decreased the mitochondrial membrane potential in cerebral cortex and striatum, whereas it had no effect on mitochondrial mass in any encephalic tissue evaluated. Finally, sulfite inhibited the activities of malate and glutamate dehydrogenase in cerebral cortex of SO-deficient rats. Taken together, our findings indicate that cerebral cortex and striatum are more vulnerable to sulfite-induced toxicity than cerebellum and hippocampus. It is presumed that these pathomechanisms may contribute to the pathophysiology of neurological damage found in patients affected by SO deficiency.
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PMID:Higher susceptibility of cerebral cortex and striatum to sulfite neurotoxicity in sulfite oxidase-deficient rats. 2752 30