Regioselectivity of hydroxylation of prostaglandins by liver microsomes supported by NADPH versus H2O2 in methylcholanthrene-treated and control rats: formation of novel prostaglandin metabolites.
Regioselectivity of hydroxylation of prostaglandins by liver microsomes supported by NADPH versus H2O2 in methylcholanthrene-treated and control rats: formation of novel prostaglandin metabolites.
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在甲基胆蒽治疗和对照大鼠中，NADPH 与 H2O2 支持的肝微粒体对前列腺素羟基化的区域选择性：新型前列腺素代谢物的形成。
DOI：
10.1016/0003-9861(85)90301-7
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发表时间：
1985
影响因子：
3.9
通讯作者：
Kupfer,D
中科院分区：
文献类型：
--
作者：
Holm,KA;Engell,RJ;Kupfer,D
用NADPH或H_2O_2对雄性大鼠肝微粒体前列腺素E_1和E_2(PGE_1和PGE_2)羟化的区域选择性进行了研究。在NADPh存在下，对照微生物体催化ω-1(C19)和ω-(C20)位的羟基化，最少生成PGE1和PGE2的新单羟基代谢物，分别称为化合物X1和X2。同样，过氧化氢支持19-羟基化和化合物X1和X2的形成，但只产生少量的20-羟基产物。在NADPH作用下，MC处理的微粒体与对照组相比，19-和20-羟基化的数量变化不大，但化合物X1的形成增加了7-11倍，X2的形成增加了10倍。与过氧化氢相比，MC处理使PGE1的19-和20-羟化增加了约3倍，X1的形成增加了35-46倍；同样，PGE2的19-和20-羟基化增加了大约2倍，X2的形成增加了10倍。这些发现表明，几种单加氧酶参与催化PGE分子不同部位的羟化反应。单加氧酶的抑制剂(SKF525A、α-萘黄酮和咪唑衍生物)进一步证明，PGES的三个位点的羟基化是由不同的P-450单加氧酶催化的。值得注意的是，与其他羟化部位相比，这些抑制剂对PGE1的20-羟化作用的影响要小得多。化合物X1和X2的结构鉴定如下。X1的PGB衍生物对高碘酸氧化的抗性和叔丁基二甲基硅基醚甲酯的质量裂解分析表明，羟化反应发生在C17或C18。最后，X1和X2的三甲基硅基醚甲酯PGB衍生物的质量裂解提供了确凿的证据，证明X1和X2分别是18-羟基-PGE1和18-羟基-PGE2。以上结果表明，PGE_1和PGE_2的高区域选择性羟化分别导致18-羟基-前列腺素E_1和18-羟基-前列腺素E_2的形成是由MC(可能是BYP-450c)诱导的BYP-450同工酶(S)催化的。
The effects of methylcholanthrene (MC) treatment of male rats on the regioselectivity of hydroxylation of prostaglandins E1and E2(PGE1and PGE2) by liver microsomes, supplemented with NADPH or H2O2, was examined. In the presence of NADPH, control microsomes catalyzed the hydroxylation at ω-1 (C19) and at ω-(C20) sites with minimal formation of novel monohydroxy metabolites of PGE1and PGE2, referred to as compounds X1and X2, respectively. Similarly, H2O2supported the 19-hydroxylation and the formation of compounds X1and X2, but yielded only minimal amounts of 20-hydroxy products. With NADPH, MC-treated microsomal incubations demonstrated only minor quantitative change in the 19- and 20-hydroxylation as compared with controls, but showed a 7- to 11-fold increase in formation of compound X1and a 10-fold increase in formation of X2. By contrast with H2O2, MC-treatment increased by about 3-fold the 19- and 20-hydroxylation of PGE1and by 35- to 46-fold the formation of X1; similarly, there was an approximate 2-fold increase in 19- and 20-hydroxylation of PGE2and a 10-fold increase in formation of X2. These findings suggest that several monooxygenases are involved in catalyzing the hydroxylation at the various sites of the PGE molecule. Inhibitors of monooxygenases (SKF 525A, α-naphthoflavone, and imidazole derivatives) provided further evidence that the hydroxylation at the three sites of PGEs is catalyzed by differentP-450 monooxygenases. It is striking that the inhibitors had a much lesser effect on the 20-hydroxylation of PGE1as compared with other sites of hydroxylation. Structural identification of compounds X1and X2was elucidated as follows. Resistance of the PGB derivative of X1to periodate oxidation and mass fragmentation analysis of thet-butyldimethylsilyl ether methyl ester, placed the hydroxylation at C17or C18. Finally, mass fragmentation of trimethylsilyl ether methyl ester PGB derivatives of X1and X2provided conclusive evidence that X1and X2are 18-hydroxy-PGE1and 18-hydroxy-PGE2, respectively. The above findings indicate that the high regioselectivity of hydroxylation of PGE1and PGE2, resulting in the formation of 18-hydroxy-PGE1and 18-hydroxy-PGE2, respectively, is catalyzed byP-450 isozyme(s) which are induced by MC, possibly byP-450c.
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研究哺乳动物肝细胞质中 NAD 依赖性脱氢酶对 omega-羟基前列腺素的氧化作用。
影响因子：
3.9
作者：
D. Kupfer;J. Navarro;G. K. Miranda;D. E. Piccolo;A. Theoharides
通讯作者：
A. Theoharides
19-羟基前列腺素 E1 是灵长类动物精液的主要成分
影响因子：
64.8
作者：
R. Kelly;P. L. Taylor;J. Hearn;R. Short;D. Martin;J. Marston
通讯作者：
J. Marston
猴子体内前列腺素 D2 的代谢。
DOI：
10.1016/s0021-9258(18)50709-2
发表时间：
1979
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. K. Ellis;M. Smigel;J. Oates;O. Oelz;B. Sweetman
通讯作者：
B. Sweetman
大鼠前列腺素 F2α 的代谢
DOI：
10.1016/0005-2760(74)90236-7
发表时间：
1974
期刊：
Biochimica et Biophysica Acta
影响因子：
--
作者：
F. Sun
通讯作者：
F. Sun
兔肝微粒体细胞色素 P-450 催化的氢过氧化物依赖性脱烷基反应的动力学。
DOI：
--
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Koop,DR;Hollenberg,PF
通讯作者：
Hollenberg,PF