Relative inactivation of steroidogenic enzyme activities of in vitro vitamin E-depleted human adrenal microsomes by lipid peroxidation.
The effects of lipid peroxidation and vitamin E on the steroidogenic activities of human adrenal microsomes were studied. The vitamin E content in the microsomes could be varied by treating the lyophilized microsomes with n-pentane, without affecting the steroidogenic enzyme activities. When the level of microsomal vitamin E in the adrenal was reduced to that in other tissues such as liver and kidney, NADPH-supported lipid peroxidation increased about 200-fold, and concomitantly, the steroidogenic enzyme activities decreased. After 5 min of the lipid peroxidation reaction, 17 alpha-hydroxylase and C17,20-lyase activities were inactivated to 13% and 18%, respectively, of the original activities. 3 beta-Hydroxysteroid dehydrogenase-isomerase and 21-hydroxylase, however, retained 89% and 84%, respectively, of the original activities. When vitamin E was reincorporated into the original activities. When vitamin E was reincorporated into the extracted microsomes, neither the lipid peroxidation reaction nor the inactivation of the enzyme activities was observed. These results indicate that the high concentration of vitamin E in adrenal protects the enzymes from oxidative damage, and that the microsomal C19 steroidogenic cytochrome P-450 activities are highly sensitive to lipid peroxidation. This suggests an association between adrenal lipid peroxidation and a decrease in C19 steroid synthesis with advancing age.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism* / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D009249:NADP / Q000494:pharmacology; D010420:Pentanes / Q000494:pharmacology; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013255:Steroid 21-Hydroxylase / Q000037:antagonists & inhibitors; D013256:Steroids / Q000096:biosynthesis*; D014810:Vitamin E / Q000502:physiology*
D008054:Lipid Peroxides; D010420:Pentanes; D013256:Steroids; D014810:Vitamin E; C033353:pentane; D008315:Malondialdehyde; D009249:NADP; D015096:3-Hydroxysteroid Dehydrogenases; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases