ω‐Oxidation of Lipoxin B4 by Rat Liver: Identification of an ω‐Carboxy Metabolite of Lipoxin B4

Yoichi Mizukami, Hideki Sumimoto, Ryuichi Isobe, Shigeki Minakami, Koichiro Takeshige

研究成果: Contribution to journalArticle査読

16 被引用数 (Scopus)

抄録

Lipoxin B4 (LXB4) is metabolized to 20‐hydroxy‐LXB4 by rat liver microsomes. The ω‐hydroxylation requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide, indicating involvement of a cytochrome P‐450 (P‐450). This is supported by inhibition of the reaction by antibodies raised against NADPH–P‐450 reductase. The P‐450 appears to be the one responsible for leukotriene B4ω‐hydroxylation, because leukotriene B4 inhibits the formation of 20‐hydroxy‐LXB4 and LXB4 blocks the leukotriene B4ω‐hydroxylase activity in microsomes. Incubation of 20‐hydroxy‐LXB4 with both rat liver cytosol and NAD+ leads to formation of a more polar metabolite on high‐performance liquid chromatography. The metabolite is identified as 20‐carboxy‐LXB4, a novel metabolite of LXB4, based on analyses by ultraviolet spectrometry and by gas chromatography/mass spectrometry. The 20‐carboxy‐LXB4‐forming activity is localized in cytosol, with an optimal pH of 8.5. The activity is dependent on NAD+, but NADP+ can not replace NAD+. The reaction is inhibited by pyrazole and 4‐methylpyrazole, inhibitors of alcohol dehydrogenase, and by substrates of the enzyme such as ethanol and 20‐hydroxy‐leukotriene B4. Disulfiram, an inhibitor of aldehyde dehydrogenase, also blocks the 20‐carboxy‐LXB4 formation. These observations suggest that both alcohol dehydrogenase and aldehyde dehydrogenase participate in the oxidation of 20‐hydroxy‐LXB4 to 20‐carboxy‐LXB4.

本文言語英語
ページ(範囲)959-965
ページ数7
ジャーナルEuropean Journal of Biochemistry
224
3
DOI
出版ステータス出版済み - 9 1994
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry

フィンガープリント 「ω‐Oxidation of Lipoxin B<sub>4</sub> by Rat Liver: Identification of an ω‐Carboxy Metabolite of Lipoxin B<sub>4</sub>」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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