Synthesis of 18-hydroxycortisol and 18-oxocortisol in bovine adrenal zona glomerulosa mitochondria.
The biosynthesis of 18-hydroxycortisol and 18-oxocortisol from cortisol was studied in calf adrenal zona glomerulosa mitochondria. Cortisol is converted to 18-hydroxycortisol and 18-oxocortisol in the same mitochondrial preparation in which corticosterone is metabolized to 18-hydroxycorticosterone and aldosterone. Cortisol and 18-hydroxycortisol interacted with mitochondria to cause a Type I differential spectrum, which was decreased by sodium dithionite. The metabolism of cortisol to 18-hydroxycortisol and 18-oxocortisol was inhibited by metyrapone in a competitive way. Cortisol was a competitive inhibitor of the transformation of corticosterone into 18-hydroxycorticosterone and aldosterone, and corticosterone was a competitive inhibitor of the transformation of cortisol into 18-hydroxycortisol and 18-oxocortisol, with a Ki very similar to the Km for the transformation of that steroid to aldosterone. These results indicate that cortisol is metabolized to 18-hydroxycortisol and 18-oxocortisol by a mitochondrial cytochrome P-450, which is the same as that which catalyzes the conversion of corticosterone into aldosterone.
Department of Internal Medicine, University of South Florida College of Medicine, Tampa.
E N
EN
Cozza
M R
MR
Chavarri
M F
MF
Foecking
C E
CE
Gomez-Sanchez
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D004227:Dithionite / Q000494:pharmacology; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D013053:Spectrophotometry; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*
D004227:Dithionite; C038135:18-oxocortisol; D000450:Aldosterone; D009249:NADP; D015069:18-Hydroxycorticosterone; C033689:18-hydroxycortisol; D003345:Corticosterone; D006854:Hydrocortisone