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Title: omega-Oxidation of lipoxin B4 by rat liver. Identification of an omega-carboxy metabolite of lipoxin B4.
Author: Mizukami Y, Sumimoto H, Isobe R, Minakami S, Takeshige K.
Journal: Eur J Biochem; 1994 Sep 15; 224(3):959-65. PubMed ID: 7925420.
Abstract:
Lipoxin B4 (LXB4) is metabolized to 20-hydroxy-LXB4 by rat liver microsomes. The omega-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 B4 omega-hydroxylation, because leukotriene B4 inhibits the formation of 20-hydroxy-LXB4 and LXB4 blocks the leukotriene B4 omega-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.

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