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.
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