Oliw E H, Lawson J A, Brash A R, Oates J A
J Biol Chem. 1981 Oct 10;256(19):9924-31.
[1-14C]Eicosatetraenoic (arachidonic) acid was incubated with a low speed (17,000 X g) rabbit renal cortical supernatant or with a cortical microsomal suspension fortified with NADPH for 15 min at 37 degrees C. The products which were less polar than prostaglandins on reversed phase high performance liquid chromatography were identified by gas chromatography-mass spectrometry. Both the fortified microsomes and the low speed supernatant formed significant amounts of two novel metabolites, 11,12-dihydroxy-5,8,14-eicosatrienoic acid and 14,15-dihydroxy-5,8,11-eicosatrienoic acid. Other identified products were 19- and 20-hydroxyeicosatetraenoic acid, 19-oxoeicosatetraenoic acid, and in the low speed supernatant, eicosatetraen-1,20-dioic acid. The metabolites were not formed in significant amounts by high speed cortical supernatant or by nonfortified cortical microsomes. Carbon monoxide inhibited formation of these compounds, indicating that they may be formed by the cytochrome P-450-linked renal monooxygenase systems.
将[1-14C]二十碳四烯酸(花生四烯酸)与低速(17,000×g)兔肾皮质上清液或添加了NADPH的皮质微粒体悬浮液在37℃孵育15分钟。通过气相色谱-质谱法鉴定了在反相高效液相色谱上比前列腺素极性小的产物。添加了NADPH的微粒体和低速上清液均形成了大量两种新的代谢产物,即11,12-二羟基-5,8,14-二十碳三烯酸和14,15-二羟基-5,8,11-二十碳三烯酸。其他鉴定出的产物为19-和20-羟基二十碳四烯酸、19-氧代二十碳四烯酸,并且在低速上清液中还有二十碳四烯-1,20-二酸。高速皮质上清液或未添加NADPH的皮质微粒体均未大量形成这些代谢产物。一氧化碳抑制这些化合物的形成,表明它们可能由细胞色素P-450相关的肾单加氧酶系统形成。