METABOLISM OF 12(S)-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID BY KIDNEYAND 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 lipoxygen ases. It is usually reduced to the corresponding hydroxy acid, 12(S)-h ydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) or it can serve as an intermediate in the biosynthesis of hepoxilins. The functions of 1 2(S)-HETE are incompletely understood but it has been proposed that it plays a role in the metastatic process of certain cancer cells, inclu ding Lewis lung carcinoma cells. 12(S)-HETE is metabolically degraded by beta- or omega-oxidation. Indirect evidence has suggested involveme nt of peroxisomes in the beta-oxidative degradation. The purpose of th e present investigation was to study 12(S)-HETE metabolism by peroxiso mes isolated from rat liver or kidney by sucrose density gradient cent rifugation. The purity of subcellular fractions was determined by mark er enzyme analyses and electron microscopy. 12(S)-HETE was quantitativ ely converted by liver or kidney peroxisomes into a single, diethyl et her-extractable metabolite. This was identified by gas-liquid chromato graphy-mass spectrometry as 8-hydroxyhexadecatrienoic acid. Lewis lung carcinoma cells also metabolized 12(S)-HETE to 8-hydroxyhexadecatrien oic acid.