Monoclonal antibody-directed characterization of rat hepatic P450 catalyzing the ω-1 and ω-2 hydroxylation of prostaglandins

Holm, Karsten A.; Park, Sang S.; Gelboin, Harry V.; Kupfer, David

doi:10.1016/0003-9861(89)90151-3

Cited by 8 publications

(1 citation statement)

References 62 publications

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“…Although the P450 NADPH-dependent metabolism of several bioactive eicosanoids is well established, P450 NAPDH-independent metabolism is less well characterized but seems to be equally important in the generation of biologically significant oxygenated eicosanoids. Although cytochromes P450 in families 1 to 3 are mainly involved in the metabolism of exogenous compounds (Nebert and Karp, 2008), several also participate in eicosanoid synthesis and degradation (Nebert and Russell, 2002), and several have been shown to catalyze -and -1-hydroxylation of prostaglandins, arachidonic acid, epoxyeicosatrienoic acids, and HETEs in an NADPH-dependent fashion (Holm et al, 1989;Tanaka et al, 1990). CYP1A2, 2E1, and 3A4 have also been shown to break down prostaglandins into 12-hydroxyheptadecatrienoate and malondialdehyde (MDA), independently of cytochrome P450 reductase, NADPH, and O 2 (Plastaras et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Human CYP2S1 Metabolizes Cyclooxygenase- and Lipoxygenase-Derived Eicosanoids

Bui¹,

Imaizumi²,

Beedanagari³

et al. 2011

Drug Metabolism and Disposition

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ABSTRACT:CYP2S1 is a recently described dioxin-inducible cytochrome P450. We previously demonstrated that human CYP2S1 oxidizes a number of carcinogens but only via the peroxide shunt. In this article, we investigated whether human CYP2S1 can metabolize cyclooxygenase-and lipoxygenase-derived lipid peroxides in a NADPHindependent fashion. Human CYP2S1 metabolizes prostaglandin ), respectively. Other cytochromes P450 such as CYP1A1, 1A2, 1B1, and 3A4 underwent similar conversions but at slower rates. The fatty acid hydroperoxides were also converted by human CYP2S1 to several epoxyalcohols. Our data indicate that fatty acid endoperoxides and hydroperoxides represent endogenous substrates of CYP2S1 and suggest that the enzyme CYP2S1 may play an important role in the inflammatory process because some of the products that CYP2S1 produces play important roles in inflammation.

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