Tanaka S, Imaoka S, Kusunose E, Kusunose M, Maekawa M, Funae Y
Department of Urology, Osaka City University Medical School, Japan.
Biochim Biophys Acta. 1990 Apr 2;1043(2):177-81. doi: 10.1016/0005-2760(90)90293-7.
The metabolism of arachidonic acid, lauric acid and prostaglandin A1 by rat hepatic microsomes and multiple forms of cytochrome P-450 purified from rat hepatic microsomes was studied. Arachidonic acid was hydroxylated by hepatic microsomes of male rats by omega- and (omega-1)-hydroxylation. Phenobarbital treatment of rats decreased the hydroxylation activity slightly, but 3-methylcholanthrene treatment increased the hydroxylation activity 2-fold. However, lauric acid and prostaglandin A1 omega- and omega-1)-hydroxylation activities decreased after treatment with phenobarbital and 3-methylcholanthrene. Arachidonic acid and lauric acid were metabolized with similar ratios of omega- and (omega-1)-hydroxylation, but prostaglandin A1 was efficiently metabolized at the omega-position by hepatic microsomes of untreated male rats. In a reconstituted system with purified cytochromes P-450, P450 UT-1, UT-2 (P-450h), MC-1 (P-450d) and MC-5 (P-450c) effectively hydroxylated arachidonic acid at both the omega- and (omega-1)-position. P450 UT-8 hydroxylated arachidonic acid only at the omega-position. P450 DM (P-450j) hydroxylated arachidonic acid at the (omega-1)-position efficiently. Lauric acid was also hydroxylated by P450 UT-1, UT-2, PB-1, PB-2, MC-1, IF-3 (P-450a) and DM, at the (omega - 1)-position only. Only P450 UT-8 could hydroxylate laruic acid at the omega-position. Prostaglandin A1 was efficiently and specifically metabolized by P450 UT-8 with omega-hydroxylation. P450 UT-2 and PB-1 could hydroxylate prostaglandin A1 by (omega-1)-hydroxylation, but with low activity.
研究了大鼠肝微粒体以及从大鼠肝微粒体中纯化出的多种细胞色素P - 450对花生四烯酸、月桂酸和前列腺素A1的代谢情况。雄性大鼠的肝微粒体通过ω-和（ω-1）-羟基化作用使花生四烯酸发生羟基化。用苯巴比妥处理大鼠会使羟基化活性略有降低，但用3-甲基胆蒽处理会使羟基化活性提高2倍。然而，用苯巴比妥和3-甲基胆蒽处理后，月桂酸和前列腺素A1的ω-和（ω-1）-羟基化活性降低。花生四烯酸和月桂酸的ω-和（ω-1）-羟基化比例相似，但未处理的雄性大鼠肝微粒体可在ω位高效代谢前列腺素A1。在含有纯化细胞色素P - 450的重组系统中，P450 UT - 1、UT - 2（P - 450h）、MC - 1（P - 450d）和MC - 5（P - 450c）能在ω-和（ω-1）位有效羟基化花生四烯酸。P450 UT - 8仅在ω位羟基化花生四烯酸。P450 DM（P - 450j）能在（ω-1）位高效羟基化花生四烯酸。月桂酸也被P450 UT - 1、UT - 2、PB - 1、PB - 2、MC - 1、IF - 3（P - 450a）和DM仅在（ω - 1）位羟基化。只有P450 UT - 8能在ω位羟基化月桂酸。前列腺素A1通过P450 UT - 8进行ω-羟基化而被高效且特异性地代谢。P450 UT - 2和PB - 1能通过（ω-1）-羟基化作用使前列腺素A1发生羟基化，但活性较低。
