Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In both guinea-pig and rat heart, mitochondrial NADH-ubiquinone-reductase and soluble DT-diaphorase accounted for 49-50% and 48-50% of menadione metabolism, respectively. Microsomal NADPH-cytochrome P450-reductase was responsible for less than 1% of menadione reduction. 2. Menadione was a high-affinity substrate for all reductases (Km values from 1 to 10 microM). 3. Marked amounts of O2-. (superoxide anion) were generated as a consequence of cardiac metabolism of menadione. 4. Menadione-induced O2-. generation was about 3-fold higher in guinea-pig than in rat heart. 5. All results were compared with data obtained on guinea-pig and rat liver.
Gen Pharmacol 1992 Jul
PMID:One- and two-electron reduction of menadione in guinea-pig and rat cardiac tissue. 139 83

Resting suspensions of cells of Saccharomyces cerevisiae grown in iron-rich or iron-deficient conditions were studied by following the fluorescence emission changes (lambda em. 400-460 nm, lambda exc. 300-340 nm) occurring in these suspensions upon addition of glucose and ferric iron. The results show that, in addition to NAD(P)H, metabolites of the aromatic amino acid pathway interfere with the fluorescence measurements, and that they could be involved in ferric iron reduction. Wild-type strains of S. cerevisiae are known to excreted anthranilic acid and 3-hydroxyanthranilic acid in response to glucose. The major fluorescing compound excreted by a chorismate-mutase-deficient mutant strain of S. cerevisiae was identified as anthranilic acid. The excretion of anthranilic and 3-hydroxyanthranilic acids was correlated with the ferric-reducing capacity of the extracellular medium. Excretion during growth was much greater by cells cultured in iron-rich medium than by cells grown in iron-deficient medium. The possibility was examined that a link could exist between the biosynthesis of aromatics and the ferri-reductase activity of the cells, via chorismate synthase and its putative diaphorase-associated activity. Two ferri-reductase-deficient mutants excreted much less 3-hydroxyanthranilate than did the parental wild-type strains. However, the ferri-reductase activity of a chorismate-synthase-deficient mutant was comparable to that of the parental strain.
J Gen Microbiol 1992 Jan
PMID:Excretion of anthranilate and 3-hydroxyanthranilate by Saccharomyces cerevisiae: relationship to iron metabolism. 155 59

The yeast Candida parapsilosis possesses two routes of electron transfer from exogenous NAD(P)H to oxygen. Electrons are transferred either to the classical cytochrome pathway at the level of ubiquinone through an NAD(P)H dehydrogenase, or to an alternative pathway at the level of cytochrome c through another NAD(P)H dehydrogenase which is insensitive to antimycin A. Analyses of mitoplasts obtained by digitonin/osmotic shock treatment of mitochondria purified on a sucrose gradient indicated that the NADH and NADPH dehydrogenases serving the alternative route were located on the mitochondrial inner membrane. The dehydrogenases could be differentiated by their pH optima and their sensitivity to amytal, butanedione and mersalyl. No transhydrogenase activity occurred between the dehydrogenases, although NADH oxidation was inhibited by NADP+ and butanedione. Studies of the effect of NADP+ on NADH oxidation showed that the NADH:ubiquinone oxidoreductase had Michaelis-Menten kinetics and was inhibited by NADP+, whereas the alternative NADH dehydrogenase had allosteric properties (NADH is a negative effector and is displaced from its regulatory site by NAD+ or NADP+).
J Gen Microbiol 1988 Dec
PMID:The alternative respiratory pathway of the yeast Candida parapsilosis: oxidation of exogenous NAD(P)H. 326 91

Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.
Arch Gen Psychiatry 1993 Mar
PMID:Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. 767 91

The distribution of neurons expressing the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) in the lateral and medial temporal lobes of schizophrenic and matched control brains was investigated in a systematic blind analysis. Schizophrenics had significantly lower numbers of NADPH-d neurons in the hippocampal formation and in the neocortex of the lateral temporal lobe but significantly greater numbers of NADPH-d neurons in the white matter of the lateral temporal lobe and a tendency toward greater numbers in parts of the parahippocampal white matter. The distorted distribution of NADPH-d neurons in the lateral temporal lobe, which may be explained by developmental disturbances, such as impaired neuronal migration or an alteration in the death cycle of transitory subcortical neurons, is similar to that found in the prefrontal cortex of schizophrenics. Alterations of cortical ontogenesis, as reflected in the distribution of NADPH-d neurons, appear to be widespread among neocortical association fields in schizophrenics and may provide a clue to the cause of the disease.
Arch Gen Psychiatry 1993 Mar
PMID:Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development. 767 92

1. An insect species, the southern armyworm Spodoptera eridania, was used as an in vivo model to examine mitomycin C's (MMC) pro-oxidant effect reflected in alterations of antioxidant enzymes. 2. Following a 2-day exposure to 0.01 and 0.05% w/w dietary concentrations, MMC only induced superoxide dismutase activity. All other enzyme activities were not affected, indicating oxidative stress was mild. 3. Following a 5-day exposure to 0.05% w/w dietary MMC, the activities of superoxide dismutase, glutathione-S-transferase and its peroxidase activity and DT-diaphorase were induced. GR activity was not altered. The high constitutive catalase activity was also not affected. These responses of S. eridania's antioxidant enzymes are analogous to those of mammalian systems in alleviating MMC-induced oxidative stress. 4. S. eridania emerges as an appropriate non-mammalian model for initial and cost-effective screening of drug-induced oxidative stress.
Gen Pharmacol 1994 May
PMID:Mitomycin C induced alterations in antioxidant enzyme levels in a model insect species, Spodoptera eridania. 792 7

Nitrate reductase from the yeast Candida nitratophila was found to contain one molecule of cytochrome b557 and one atom of molybdenum per subunit. FAD/haem-dependent diaphorase activity (haem domain) was associated with a 40 kDa tryptic fragment of the subunit. The 50 amino-terminal residues of this fragment were determined, and the sequence did not show significant similarity to deduced sequences of other nitrate reductases previously published. Increasing ionic strength in vitro had a stimulatory effect on enzymic activity via stimulation of the molybdenum-dependent terminal nitrate-reducing activity. Stimulation of activity by exogenous protein (bovine serum albumin or casein) also appeared to be an ionic effect. Stimulation of catalytic activity by phosphate was a separate effect.
J Gen Microbiol 1993 Mar
PMID:Further characterization of the assimilatory nitrate reductase from the yeast Candida nitratophila. 847 56

1. The metabolism of the benzoquinone 2,5-dimethylbenzoquinone and of the naphthoquinone 2,3-dimethoxy-1,4-naphthoquinone was studied in subcellular fractions isolated from cardiac tissue of guinea pig and rat. 2. In both species the benzoquinone was mainly metabolized through the mitochondrial NADH-ubiquinone-oxidoreductase, whereas the naphthoquinone was metabolized to approximately equal extents by mitochondrial reductase and by soluble DT-diaphorase. 3. Guinea pig heart metabolized 3 times more naphthoquinone than rat heart. 4. As a consequence of quinone metabolism, marked amounts of O2- center dot - were generated; naphthoquinone-induced O2- center dot - generation was about 4-fold higher in guinea pig than in rat heart.
Gen Pharmacol 1995 Dec
PMID:Metabolism of simple quinones in guinea pig and rat cardiac tissue. 874 66

1. Mitomycin C (MMC) is considered to be the prototype bioreductive drug undergoing activation to toxic species preferentially under hypoxic conditions. Therefore a proper understanding of the enzymology of bioreduction in tumor tissue is of great importance. 2. DT-diaphorase and NADPH:cytochrome P-450 reductase (quinone reductases) are believed to have established roles in this activation pathway, but these roles are now undergoing revision. 3. It is emerging, however, that different reductases prevail under different physiological conditions. Indeed, DT-diaphorase has been found to protect cells from the hypoxic cytotoxicity of MMC in cell lines expressing high levels of the enzyme. 4. A novel mitochondrial reductase(s) has been identified in solid tumor tissue and is active only under hypoxic conditions and is more efficient at metabolizing MMC than are the other reductases identified. 5. Thus, this newly identified mitochondrial reductase(s) is a potential new target for enzyme-directed bioreductive drug therapy if tumor hypoxia can be achieved. However, because most tumors overexpress DT-diaphorase, this enzyme may prove optimal for MMC drug therapy.
Gen Pharmacol 1998 Oct
PMID:Current issues in the enzymology of mitomycin C metabolic activation. 979 12

Using combined nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) histochemistry and salmon gonadotropin-releasing hormone (sGnRH) immunocytochemistry, it is reported for the first time that possible potential contacts occur between the nitric oxide (NO)- and the GnRH-containing neurons in the brain of a freshwater teleost, Rhodeus amarus. GnRH-immunoreactive (ir) neurons were observed in the olfactory nerve (OLN), olfactory bulb (OB), medial olfactory tract (MOT), ventral telencephalon (VT), nucleus preopticus periventricularis (NPP), nucleus lateralis tuberis (NLT), and midbrain tegmentum (MT). Although NADPHd neurons were widely distributed in the brain, only those having an association with GnRH-ir neurons are described. Based on the nature of the association between the GnRH and the NADPHd neurons, the former were classified into three types. The Type I GnRH neurons were characterized by the presence of NADPHd-positive granules in the perikarya and processes and occurred in the OLN, OB, MOT, and VT. The Type II GnRH neurons, having soma-soma or soma-process contacts with the NADPHd neurons, were restricted to the MT; the long processes of NADPHd cells crossed over either the perikarya or the thick processes of GnRH cells. However, the Type III GnRH neurons, found in the NPP and NLT, did not show direct contact, but a few NADPHd fibers were present in the vicinity. The terminal-soma contacts in the olfactory system and the VT and the soma-soma contacts in the MT represent the sites of possible potential contacts indicating a direct NO involvement in GnRH function, although NO action by diffusion remains possible. NO may influence the NPP and NLT GnRH cells by diffusion only, since a direct contact was not observed.
Gen Comp Endocrinol 2000 Oct
PMID:Gonadotropin-releasing hormone-immunoreactive neurons and associated nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in the brain of a teleost, Rhodeus amarus. 1104 10


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