Oxidative Metabolism of a Fatty Acid Amide Hydrolase-Regulated Lipid, Arachidonoyltaurine

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• 作者：Melissa V. Turman ; Philip J. Kingsley ; Carol A. Rouzer ; Benjamin F. Cravatt ; Lawrence J. Marnett
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：March 25, 2008
• 年：2008
• 卷：47
• 期：12
• 页码：3917 - 3925
• 全文大小：385K
• 年卷期：v.47,no.12(March 25, 2008)
• ISSN：1520-4995

文摘

A novel class of lipids, N-acyltaurines, was recently discovered in fatty acid amide hydrolase knockout mice. In some peripheral tissues, such as liver and kidney, N-acyltaurines with long, polyunsaturated acyl chains are most prevalent. Polyunsaturated fatty acids are converted to a variety of signaling molecules by cyclooxygenases (COXs) and lipoxygenases (LOXs). The ability of COXs and LOXs to oxygenate arachidonoyltaurine was evaluated to gain insight into the potential metabolic fate of N-acyltaurines. Although arachidonoyltaurine was a poor substrate for COXs, mammalian 12S- and 15S-LOXs oxygenated arachidonoyltaurine with similar or better efficiency than arachidonic acid. Products of arachidonoyltaurine oxygenation were characterized by liquid chromatography−tandem mass spectrometry (LC−MS/MS). The positional specificity of single oxygenation was retained for 15S-LOXs. However, platelet-type 12S-LOX produced 12- and 15-hydroxyeicosatetraenoyltaurines (HETE-Ts). Furthermore, LOXs generated dihydroxyeicosatetraenoyltaurines (diHETE-Ts). Metabolism of arachidonoyltaurine by murine resident peritoneal macrophages (RPMs) was also profiled. Arachidonoyltaurine was rapidly taken up and converted primarily to 12-HETE-T. Over prolonged incubations, RPMs also generated small amounts of diHETE-T. Oxidative metabolism of polyunsaturated N-acyltaurines may represent a pathway for the generation or termination of novel signaling molecules.