Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.8.1.4 (diaphorase)
 2,754 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ESR spectroscopic evidence is presented for the formation of vanadium(IV) in the reduction of vanadium(V) by three typical, NADPH-dependent, flavoenzymes: glutathione reductase, lipoyl dehydrogenase, and ferredoxin-NADP+ oxidoreductase. The vanadium(V)-reduction mechanism appears to be an enzymatic one-electron reduction process. Addition of superoxide dismutase (SOD) showed that the generation of vanadium(IV) does not involve the superoxide (O2-) radical significantly. Measurements under anaerobic atmosphere showed, however, that the enzymes-vanadium-NADPH mixture can cause the reduction of molecular oxygen to generate H2O2. The H2O2 and vanadium(IV) thus formed react to generate hydroxyl (.OH) radical. The .OH formation is inhibited strongly by catalase and to a lesser degree by SOD, but it is enhanced by exogenous H2O2, suggesting the occurrence of a Fenton-like reaction. The inhibition of vanadium(IV) formation by N-ethylmaleimide indicates that the SH group on the flavoenzyme's cystine residue plays an important role in the enzyme's vanadium(V) reductase function. These results thus reveal a new property of the above-mentioned, NADPH-dependent flavoenzymes--their function as vanadium(V) reductases, as well as that as generators of .OH radical in the vanadium(V) reduction mechanism.
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PMID:Flavoenzymes reduce vanadium(V) and molecular oxygen and generate hydroxyl radical. 165 58

This study reports a new property of the important NAD(P)H-dependent flavoenzymes, glutathione reductase, lipoyl dehydrogenase and ferredoxin-NADP+ oxidoreductase, that can catalyze a one electron reduction of metal ions such as chromium(VI) and vanadium(V). During the enzymatic reduction process, molecular oxygen is reduced to H2O2, which reacts with the reduced metal complexes to generate hydroxyl radicals. Since the hydroxyl radicals have been suggested to play an important role in Cr(VI) toxicity, this study provides a basis for a recent observation that Cr(VI) mutagenesis is strongly oxygen dependent. These results also point to an enzymatic pathway for the metabolism of some metal ions and concomitant generation of hydroxyl radicals.
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PMID:NADPH-dependent flavoenzymes catalyze one electron reduction of metal ions and molecular oxygen and generate hydroxyl radicals. 217 63

The biochemical mechanism underlying vanadate-stimulated NAD(P)H oxidation is controversial. Some reports favor an exclusive role for a superoxide (O2(-)-mediated radical chain reaction, while others cite data that suggest a contribution from O2(-)-independent enzymatic pathways. We recently reported that a vanadium(IV) species accumulates over a period of about 30 min in phosphate-buffer mixtures of vanadate, NAD(P)H, and a flavoenzyme such as glutathione reductase, lipoyl dehydrogenase, or ferredoxin-NADP+ oxidoreductase. The concentration of this vanadium(IV) species was found to depend critically on the simultaneous presence of the enzyme and NAD(P)H, but not on superoxide dismutase, or a nitrogen atmosphere. It was thus concluded that the flavoenzyme/NAD(P)H system acts as a vanadate reductase. However, a subsequent report put forth an alternative hypothesis in which the accumulation of this vanadium(IV) species is ascribed to direct reduction of vanadate by NAD(P)H itself, starting when buffer-dissolved molecular O2 and H2O2 have been depleted. We have reexamined our earlier data, and carried out new measurements to evaluate the effect of dissolved oxygen and related factors on the kinetics of vanadium(IV) generation in vanadate/NAD(P)H/flavoenzyme mixtures. The new data support our earlier suggestion that the above-mentioned flavoenzymes can indeed act as NAD(P)H-dependent vanadate reductases.
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PMID:One-electron reduction of vanadium(V) by flavoenzymes/NADPH. 838 2

Rabbits given 1 ppm of vanadate in drinking water for twelve months showed (a) increased plasma levels of catecholamines (b) reduction of the arterial concentration of nitric oxide (c) lower activity of urine kallikrein and higher activities of urine kininases I and II and enkephalinase (d) reduced cardiac inotropism and augmented total peripheral resistance, with unchanged blood pressure levels (e) accumulation of the metal in the aorta and cardiac ventricles. Monoaminooxidase and glucose-6-phosphate dehydrogenase activities were increased by vanadate in both kidney and liver and that of NADH-diaphorase in the kidney, in which NADPH-diaphorase activity was reduced. Some of the above results were also obtained in rats given 10 and 40 ppm of vanadate in drinking water for six-seven months; these animals showed arterial hypertension and reduced activity of Na, K-ATPase in the kidney. Vanadium appears to act on the cardiovascular function through selective neurohumoral, autacoidal and transductional mechanisms only in part depending on the species.
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PMID:[Neurohumoral, autacoid and transductional mechanisms in the cardiovascular effects of vanadate: histochemical correlations]. 937 36