Lauric acid hydroxylation in human liver and kidney cortex microsomes.
Lauric acid hydroxylation in human liver and kidney cortex microsomes.
复制标题
人肝和肾皮质微粒体中的月桂酸羟基化。
DOI：
10.1016/0006-2952(79)90077-7
复制
发表时间：
1979
影响因子：
5.8
通讯作者：
B. Masters
中科院分区：
文献类型：
--
作者：
R. Okita;S. Jakobsson;R. Prough;B. Masters
在7具人体尸体的肝脏和肾脏皮层微粒体中，研究了中链脂肪酸（十二烷酸或月桂酸）的ω-和(ω- 1)-羟基化。在人肝微粒体中月桂酸羟基化的速率被发现比在人肾皮质微粒体中记录的速率高出4到30倍。7个人肾月桂酸羟基化的平均比活性比猪、大鼠或仓鼠肾微粒体的比活性低6 ~ 14倍。我们还研究了几种已知的肝微粒体细胞色素p -450依赖性单加氧酶系统抑制剂的作用。Metyrapone优先抑制人肝微粒体(ω- 1)-羟化酶活性，但不影响ω-羟化反应。在7,8-苯甲黄酮存在下，人肝微粒体(ω- 1)-羟化酶活性受到刺激，但对ω-羟化反应有抑制作用。2-二乙胺乙基-2,2-二苯基戊酸酯（SKF 525A）抑制人肝微粒体中这两种羟化酶的活性。metyrapone和SKF 525A均未抑制人肾微粒体催化的月桂酸羟基化反应。这些研究表明，人类肾脏皮质微粒体中细胞色素p -450介导的中链脂肪酸羟基化活性远低于其他被研究物种的肾脏。抑制剂metyrapone和SKF 525A对人肝脏和肾脏微粒体中月桂酸盐ω-和(ω- 1)-羟基化的影响与在其他哺乳动物中报道的影响相似。
The ω- and (ω- 1 )-hydroxylation of the medium-chain fatty acid, dodecanoic or lauric acid, was studied in liver and kidney cortex microsomes from seven human cadavers. The rates of laurate hydroxylation in human liver microsomes were found to exceed the rates recorded in human kidney cortex microsomes by 4-to 30-fold. The mean specific activity of laurate hydroxylation from the seven human kidneys was six to fourteen times lower than the specific activities found in pig, rat or hamster kidney microsomes. The effects of several known inhibitors of the liver microsomal cytochrome P-450-dependent mono-oxygenase system were also studied. Metyrapone preferentially inhibited the (ω- 1)-hydroxylase activity of human liver microsomes, but did not affect the ω-hydroxylation reaction. In the presence of 7,8-benzoflavone, the human liver microsomal (ω- 1 )-hydroxylase activity was stimulated, but an inhibitory effect was observed on the ω-hydroxylation reaction. 2-Diethylaminoethyl-2,2-diphenylvaIerate (SKF 525A) inhibited both hydroxylase activities in human liver microsomes. Neither metyrapone nor SKF 525A inhibited the laurate hydroxylation reactions catalyzed by human kidney microsomes. These studies indicate that the cytochrome P-450-mediated hydroxylations of medium chain fatty acids in human kidney cortex microsomes are much less active than in kidneys of other species investigated. The effects of the inhibitors, metyrapone and SKF 525A, on ω- and (ω- 1)-hydroxylation of laurate in human liver and kidney microsomes were similar to the effects reported in other mammalian species.