Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Temporal aspects of the effects of inhibitors on hepatic cytochrome P-450 destruction and lipid peroxidation induced by NADPH and linoleic acid hydroperoxide (LAHP) were compared. In the absence of added Fe2+, NADPH-induced lipid peroxidation in hepatic microsomes exhibited a slow phase followed by a fast phase. The addition of Fe2+ eliminated the slow phase, thus demonstrating that iron is a rate-limiting component in the reaction. EDTA, which complexes iron, and p-chloromercurobenzoate (pCMB), which inhibits NADPH-cytochrome P-450 reductase, inhibited both phases of the reaction. Catalase as well as scavengers of hydroxyl radical, inhibited NADPH-induced lipid peroxidation almost completely. GSH also inhibited the NADPH-dependent reaction but only when added at the beginning of the reaction. In contrast with NADPH-dependent lipid peroxidation, the autocatalytic reaction induced by LAHP was not biphasic, NADPH-dependent or iron-dependent, nor was it inhibited by hydroxyl radical scavengers, catalase or GSH. A synergistic effect on lipid peroxidation was observed when both NADPH and LAHP were added to microsomes. It is concluded that both the fast and slow phases of NADPH-dependent microsomal lipid peroxidation are catalyzed enzymatically and are dependent upon Fe2+, whereas LAHP-dependent lipid peroxidation is autocatalytic. Since the fast phase of enzymatic lipid peroxidation occurred during the fast phase of destruction of cytochrome P-450, it is postulated that iron made available from cytochrome P-450 is sufficient to promote optimal lipid peroxidation. Since catalase and hydroxyl radical scavengers inhibited NADPH-dependent but not LAHP-dependent lipid peroxidation, it is concluded that the hydroxyl radical derived from H2O2 is the initiating active-oxygen species in the enzymatic reaction but not in the autocatalytic reaction.
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PMID:NADPH- and linoleic acid hydroperoxide-induced lipid peroxidation and destruction of cytochrome P-450 in hepatic microsomes. 357 83

The generation of hydroxyl free radicals in the system consisting of purified NADPH-cytochrome P-450 reductase and anticancer quinone drugs, such as carbazilquinone, mitomycin C, aclacinomycin A and adriamycin, has been confirmed by two methods. In the spin trapping study, using N-tert-butyl-alpha-phenylnitrone as the spin trapping agent, four drugs generated hydroxyl radical-trapped signals, and the formation of the spin adduct was dependent on time and the enzyme concentration. Among the four drugs, the generation time of signal was in the order of carbazilquinone, aclacinomycin A, adriamycin and mitomycin C, but the magnitude of signal intensity was different. In both aclacinomycin A and adriamycin, the signal disappeared in a few minutes. Catalase completely inhibited the formation of the spin adduct, while superoxide dismutase did not significantly inhibit, but effected in some manner. The generation of hydroxyl radical was also confirmed by the ethylene production from methional. Among the four drugs, the order of the magnitude of ethylene production was different from that of signal intensity by ESR study. Catalase potently inhibited the ethylene production, while superoxide dismutase effected in some manner. From these results, the interactions of anticancer quinone drugs with NADPH-cytochrome P-450 reductase and oxygen, and the possible relations of the enzymes to the radical related actions of these drugs are discussed.
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PMID:Generation of hydroxyl radical by anticancer quinone drugs, carbazilquinone, mitomycin C, aclacinomycin A and adriamycin, in the presence of NADPH-cytochrome P-450 reductase. 629 7

The incubation of lambda DNA in the reaction system of alloxan plus NADPH-cytochrome P450 reductase (fp2) in the presence of ferritin caused strand breaks after a lag time of about 5 min. Addition of ferritin to the reaction system at concentrations below 50 micrograms/ml caused the strand breaks of DNA in a concentration-dependent fashion. Catalase, scavengers of hydroxyl radicals (HO.) and iron-chelators almost completely inhibited the DNA strand breaks, but superoxide dismutase (SOD) did not, suggesting that the strand breaks are induced by the generation of HO. via the reaction of H2O2 and Fe(II), namely, the Fenton reaction. When the ferritin was incubated in the reaction system of alloxan plus fp2, the iron release from ferritin increased with incubation time depending on the amount of fp2. The addition of increasing concentrations of ferritin to the reaction system resulted in progressive increase in the iron release and a decrease in the electron spin resonance signal intensity of alloxan radical (HA.), the one electron reduced form of alloxan, suggesting that HA. generated in the reaction system is capable of releasing iron from ferritin. These results support the possibility that the iron released from ferritin may be involved in the diabetogenic action of alloxan.
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PMID:Effect of ferritin on lambda DNA strand breaks in the reaction system of alloxan plus NADPH-cytochrome P450 reductase: ferritin's role in diabetogenic action of alloxan. 774 95

NADPH-cytochrome1 P450 reductase and DT-diaphorase catalyze and one- and two-electron reduction of adrenochrome to its o-semiquinone and o-hydroquinone, respectively. Under aerobic conditions both adrenochrome o-semiquinone and o-hydroquinone proved to be unstable, undergoing autoxidation with concomitant oxygen consumption and continuous NADPH and NADH oxidation. Molecular oxygen was found to play a predominant role in autoxidation of o-semiquinone during reduction of adrenochrome catalyzed by NADPH-cytochrome P450 reductase. In addition, molecular oxygen, in the presence of manganese, was found to be responsible for the majority of autoxidation of o-semiquinone. However, the role of superoxide radicals in the autoxidation of leucoadrenochrome during the reduction of adrenochrome by DT-diaphorase was found to be predominant. Catalase different significantly with respect to NADPH and NADH oxidation during reduction of adrenochrome catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase. Catalase increased NADPH oxidation slightly, while NADH oxidation was inhibited during reduction of adrenochrome by NADPH cytochrome P450 reductase and DT-diaphorase, respectively. The presence of manganese in the incubation mixture was found to increase the prooxidant role of catalase on autoxidation during one-electron reduction of aminochrome catalyzed by NADPH cytochrome P450 reductase. A marked difference in the inhibitory effect of superoxide dismutase on oxygen consumption during adrenochrome reduction catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase was also observed. A possible mechanism for reduction of adrenochrome by NADPH-cytochrome P450 reductase and DT-diaphorase and a role for superoxide dismutase and catalase are proposed.
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PMID:Effects of superoxide dismutase and catalase during reduction of adrenochrome by DT-diaphorase and NADPH-cytochrome P450 reductase. 859 36

The reduction of hexavalent chromium, Cr(VI), can generate reactive Cr intermediates and various types of oxidative stress. The potential role of human microsomal enzymes in free radical generation was examined using reconstituted proteoliposomes (PLs) containing purified cytochrome b(5) and NADPH:P450 reductase. Under aerobic conditions, the PLs reduced Cr(VI) to Cr(V) which was confirmed by ESR using isotopically pure (53)Cr(VI). When 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) was included as a spin trap, a very prominent signal for the hydroxyl radical (HO()) adduct was observed as well as a smaller signal for the superoxide (O(2)(-)) adduct. These adducts were observed even at very low Cr(VI) concentrations (10 muM). NADPH, Cr(VI), O(2), and the PLs were all required for significant HO() generation. Superoxide dismutase eliminated the O(2)(-) adduct and resulted in a 30% increase in the HO() adduct. Catalase largely diminished the HO() adduct signal, indicating its dependence on H(2)O(2). Some sources of catalase were found to have Cr(VI)-reducing contaminants which could confound results, but a source of catalase free of these contaminants was used for these studies. Exogenous H(2)O(2) was not needed, indicating that it was generated by the PLs. Adding exogenous H(2)O(2), however, did increase the amount of DEPMPO/HO() adduct. The inclusion of formate yielded the carbon dioxide radical adduct of DEPMPO, and experiments with dimethyl sulfoxide (DMSO) plus the spin trap alpha-phenyl-N-tert-butylnitrone (PBN) yielded the methoxy and methyl radical adducts of PBN, confirming the generation of HO(). Quantification of the various species over time was consistent with a stoichiometric excess of HO() relative to the net amount of Cr(VI) reduced. This also represents the first demonstration of a role for cytochrome b(5) in the generation of HO(). Overall, the simultaneous generation of Cr(V) and H(2)O(2) by the PLs and the resulting generation of HO() at low Cr(VI) concentrations could have important implications for Cr(VI) toxicity.
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PMID:Reduction of hexavalent chromium by human cytochrome b5: generation of hydroxyl radical and superoxide. 1732 Jul 57