Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac mitochondrial NADH dehydrogenase (Cytochrome c reductase, EC1.6.99.3) catalyses the reduction of ferricytochrome c to ferrocytochrome c by NADH. In the presence of the anthracycline anti-tumour drug, adriamycin, electron transfer from NADH is subverted to dioxygen. Using the electron spin resonance technique of spin trapping with the spin trapping agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) adriamycin was found to stimulate the formation of superoxide and hydroxyl radicals in the NADH/NADH dehydrogenase reaction. Hydroxyl radical formation is dependent on the availability of trace amounts of redox active metal ions - particularly ferric ions. Trace amounts of ferric ions catalyse the formation of hydroxyl radicals by both superoxide-dependent and adriamycin-dependent one electron reduction of hydrogen peroxide. The metabolism of adriamycin by cardiac mitochondrial NADH dehydrogenase may be an important etiological factor in adriamycin-induced cardiotoxicity. It may be therapeutically beneficial to keep nonessential ferric/ferrous ions in the myocardium at minimum levels with siderophoric iron chelators - providing the anti-tumour activity of adriamycin is not impaired.
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PMID:Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. 285 Feb 70

Mo reductase (MoR; formerly cytochrome c reductase) fragments of NADH:NO(3) reductase (NR; EC1.6.6.1) were cytosolically expressed in Pichia pastoris, a methylotrophic yeast, using spinach (Spinacia oleracea) and corn (Zea maize) cDNAs. In fermenter cultures, spinach MoR was expressed at 420 mg L(-1), corn MoR at 32 mg L(-1), and corn MoR plus with putative NR interface domain N terminus (MoR+) at 17 mg L(-1). Constitutively expressed MoR+ was structurally stable while it was degraded when expressed by methanol induction, which suggests methanol growth produces more proteinase. Methanol-induced expression yielded more target protein. All three MoR were purified to homogeneity and their polypeptides were approximately 41 (MoR) and approximately 66 (MoR+) kD. MoR was monomeric and MoR+ dimeric, confirming the predicted role for dimer interface domain of NR. MoR+, although differing in quaternary structure from MoR, has similar kinetic properties for ferricyanide and cytochrome c reductase activities and visible spectra, which were like NR. Redox potentials of MoR and MoR+ were similar for flavin, whereas MoR+ had a more negative potential for heme-iron. Reaction schemes for MoR catalyzed reactions were proposed based on fast-reaction rapid-scan stopped-flow kinetic analysis of MoR. P. pastoris is an excellent system for producing the large amounts of NR fragments needed for detailed biochemical studies.
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PMID:Recombinant expression of molybdenum reductase fragments of plant nitrate reductase at high levels in Pichia pastoris. 1085 4