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Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β ...
18-Hydroxylase (aldosterone synthase) – mineralocorticoid synthesis; 21-Hydroxylase – corticosteroid synthesis; Cytochrome P450 (CYP1, 2, 3) – estrogen metabolism; Hydroxysteroid dehydrogenases (and ketosteroid reductases) 3α-Hydroxysteroid dehydrogenase – androgen, progestogen, and neurosteroid synthesis and metabolism
These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions), but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona glomerulosa and zona fasciculata.
Corticosterone is converted to aldosterone by aldosterone synthase, found only in the mitochondria of glomerulosa cells. Glomerulosa cells are found in the zona glomerulosa , which is the most superficial region of endocrine cells in the adrenal cortex .
This layer is the main site for production of aldosterone, a mineralocorticoid, by the action of the enzyme aldosterone synthase. [16] [17] Aldosterone plays an important role in the long-term regulation of blood pressure. [18]
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Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are in the kidney, on cells of the late distal convoluted tubule and medullary collecting duct. In the principal cells aldosterone increases activity of basolateral membrane sodium-potassium ATPase and apical epithelial sodium channels, ENaC ...
[123] [124] Even smaller amounts of progesterone may be also hydroxylated via 11β-hydroxylase (CYP11B1) and to a lesser extent via aldosterone synthase (CYP11B2) into 11β-hydroxyprogesterone. [125] [126] [44] In addition, progesterone can be hydroxylated in the liver by other cytochrome P450 enzymes which are not steroid-specific.