METABOLISM OF 12(S)-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID BY KIDNEY AND LIVER PEROXISOMES

12(S)-Hydroperoxy-5,8,10,14-eicosatetraenoic acid (12(S)-HPETE) is one of the main products formed from arachidonic acid by animal lipoxygenases. It is usually reduced to the corresponding hydroxy acid, 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) or it can serve as an intermediate in the biosynthesis of hepoxilins. The functions of 12(S)-HETE are incompletely understood but it has been proposed that it plays a role in the metastatic process of certain cancer cells, including Lewis lung carcinoma cells. 12(S)-HETE is metabolically degraded by beta- or omega-oxidation. Indirect evidence has suggested involvement of peroxisomes in the beta-oxidative degradation. The purpose of the present investigation was to study 12(S)-HETE metabolism by peroxisomes isolated from rat liver or kidney by sucrose density gradient centrifugation. The purity of subcellular fractions was determined by marker enzyme analyses and electron microscopy. 12(S)-HETE was quantitatively converted by liver or kidney peroxisomes into a single, diethyl ether-extractable metabolite. This was identified by gas-liquid chromatography-mass spectrometry as 8-hydroxyhexadecatrienoic acid. Lewis lung carcinoma cells also metabolized 12(S)-HETE to 8-hydroxyhexadecatrienoic acid.