Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis.
Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000, SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.
D015069:18-Hydroxycorticosterone / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011863:Radioimmunoassay
D008293:Malates; D009243:NAD; D000450:Aldosterone; D009249:NADP; D015069:18-Hydroxycorticosterone; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D003345:Corticosterone