The effect of ether stress and cycloheximide treatment on cholesterol binding and enzyme turnover of adrenal cortical cytochrome P450scc.
Relative rate constants for the formation of pregnenolone from cytochrome P450scc bound cholesterol in adrenal cortical mitochondria of stressed, stressed plus cycloheximide treated and dexamethasone treated rats were calculated from the ratios of initial rates of pregnenolone formation and the pregnenolone induced difference spectrum. In mitochondria from adrenals removed under aerobic conditions in vivo, the rate constant for the enzyme in stressed rats is twice a high as the rate constant for the enzyme from the stressed plus cycloheximide group, and four times as high as that for the enzyme from dexamethasone treated rats. Anoxia for 5 min in the intact gland increases the rate constant in all groups. Pregnenolone difference spectra are higher in mitochondria from stressed plus cycloheximide treated rats than in mitochondria from stressed rats, when adrenals are removed aerobically. It is concluded that ACTH increases cholesterol binding to cytochrome P450scc, by increasing either the enzymes affinity for its substrate or the availability of cholesterol and in addition promotes turnover of the enzyme. Both of these effects of ACTH are inhibited by cycloheximide.
D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology*; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004986:Ether; D005260:Female; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D011284:Pregnenolone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D013312:Stress, Physiological / Q000139:chemically induced / Q000378:metabolism*
D004986:Ether; D000616:Aminoglutethimide; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D003513:Cycloheximide; D010100:Oxygen