Oxidative metabolism of a fatty acid amide hydrolase-regulated lipid, arachidonoyltaurine.
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 12 S- and 15 S-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 15 S-LOXs. However, platelet-type 12 S-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.
Turman
Melissa V
MV
A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Kingsley
Philip J
PJ
Rouzer
Carol A
CA
Cravatt
Benjamin F
BF
Marnett
Lawrence J
LJ
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D002853:Chromatography, Liquid; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D010084:Oxidation-Reduction; D013654:Taurine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001095:Arachidonic Acids; D051546:Cyclooxygenase 2; D013654:Taurine; D000099252:Fatty Acid Amide Hydrolases; C529118:arachidonoyltaurine