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Formation of a novel 20‐hydroxylated metabolite of lipoxin A 4 by human neutrophil microsomes
Author(s) -
Sumimoto Hideki,
Isobe Ryuichi,
Mizukami Yoichi,
Minakami Shigeki
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81165-v
Subject(s) - chemistry , metabolite , hydroxylation , microsome , arachidonic acid , lipoxin , leukotriene b4 , hydroxyeicosatetraenoic acid , biochemistry , monooxygenase , cytochrome p450 , chromatography , enzyme , biology , inflammation , receptor , immunology
Lipoxin A 4 (LXA 4 ) is a biologically active compound produced from arachidonic acid via interactions of lipoxygenases. Incubation of LXA 4 either with human neutrophils or with the neutrophil microsomes leads to formation of a polar compound on a reverse‐phase high‐performance liquid chromatography. We have identified the metabolite as 20‐hydroxy‐LXA 4 , a novel metabolite of arachidonic acid, on the basis of ultraviolet spectrometry and gas chromatography‐mass spectrometry. The LXA 4 ω ‐hydroxylation requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide, by antibodies raised against NADPH‐cytochrome P‐450 reductase, or competitively by leukotriene B 4 (LTB 4 ) and LTB 5 , substrates of LTB 4 ω‐hydroxylase. These findings indicate that the formation of 20‐hydroxy‐LXA 4 is catalyzed by a neutrophil cytochrome P‐450, the LTB 4 ω‐hydroxylase.