Formation of a novel 20‐hydroxylated metabolite of lipoxin A4 by human neutrophil microsomes

FEBS Letters

Sumimoto, Hideki²  Isobe, Ryuichi¹  Minakami, Shigeki²  Mizukami, Yoichi² 

[1] Faculty of Pharmaceutical Science, Kyushu University, Fukuoka 812, Japan;Department of Biochemistry, Kyushu University School of Medicine, Fukuoka 812, Japan

关键词: Lipoxin A4;    ω-Hydroxylation;    Cytochrome P-450;    Human neutrophil;    LXA4;    lipoxin A4 or (5S;    6R;    15S)-5;    6;    15-trihydroxy-7;    9;    11;    13-E;    E;    Z;    E-eicosatetraenoic acid;    20-OH-LXA4;    20-hydroxy-LXA4 or (5S;    6R;    15S)-5;    6;    15;    20-tetrahydroxy-7;    9;    11;    13-E;    E;    Z;    E-eicosatetraenoic acid;    LXB4;    lipoxin B4;    LTB4;    leukotriene B4;    20-OH-LTB4;    20-hydroxy-LTB4;    PGA1 prostaglandins A1;    P-450;    cytochrome P-450;    P-450LTBω;    cytochrome P-450LTBω or human neutrophil LTB4 ω-hydroxylase.;   

DOI  :  10.1016/0014-5793(93)81165-V

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lipoxin A₄ (LXA₄) is a biologically active compound produced from arachidonic acid via interactions of lipoxygenases. Incubation of LXA₄ 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-LXA₄, a novel metabolite of arachidonic acid, on the basis of ultraviolet spectrometry and gas chromatography-mass spectrometry. The LXA₄ω -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 B₄ (LTB₄) and LTB₅, substrates of LTB₄ ω-hydroxylase. These findings indicate that the formation of 20-hydroxy-LXA₄ is catalyzed by a neutrophil cytochrome P-450, the LTB₄ ω-hydroxylase.

【 授权许可】

Unknown