Production of reactive oxygen species by microsomes enriched in specific human cytochrome P450 enzymes

Susana Puntarulo, Arthur I. Cederbaum

Research output: Contribution to journalArticlepeer-review

227 Scopus citations


Few studies have evaluated the production of reactive oxygen intermediates by human microsomes, especially the influence of the specific form of cytochrome P450. Experiments were carded out to evaluate the ability of CYP1A 1, 1A2, 2B6, and 3A4 to consume NADPH, reduce iron, and catalyze production of reactive oxygen species. Microsomes enriched in each of these CYPs were obtained from commercial ± lymphoblast cells that had been transfected with cDNA encoding the specific human CYP. On a per nanomole cytochrome P450 basis, CYP3A4 was the most active P450 evaluated in catalyzing NADPH oxidation, production of superoxide anion radical, NADPH dependent chemiluminescence, oxidation of dichlorofluorescein diacetate, and reduction of either ferric-EDTA or ferric-citrate. CYP1A1 was the next most reactive CYP, whereas CYP1A2 and 2B6 displayed a comparable, lower activity. Nitric oxide, which reacts with and inactivates hemoproteins, inhibited superoxide production by all the CYPs to a similar extent. Because CYP3A4 is present in high amounts in human liver microsomes and is active in catalyzing the formation of reactive oxygen species, this CYP may make an important contribution in the overall ability of human liver microsomes to generate active oxygen species.

Original languageEnglish
Pages (from-to)1324-1330
Number of pages7
JournalFree Radical Biology and Medicine
Issue number7-8
StatePublished - May 1998


  • CYP1A1
  • CYP1A2
  • CYP2B6
  • CYP3A4
  • Free radical
  • Human cytochrome P450s
  • Iron reduction
  • Reactive oxygen species
  • Superoxide anion


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