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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 ...
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.
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
The genes encoding aldosterone synthase and 11β-hydroxylase are 95% identical and are close together on chromosome 8.In individuals with GRA, there is unequal crossing over so that the 5' regulatory region of the 11-hydroxylase gene is fused to the coding region of the aldosterone synthase.
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The outermost layer, the zona glomerulosa is the main site for the production of aldosterone, a mineralocorticoid. The synthesis and secretion of aldosterone are mainly regulated by the renin–angiotensin–aldosterone system. The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2).
Cortisol and aldosterone deficits are associated with life-threatening sodium loss, as the steroids play roles in regulating sodium homeostasis. Simple-virilizing CAH patients (~1-2% enzyme function) [ 58 ] maintain adequate sodium homeostasis, but exhibit other symptoms shared by the salt-wasting form, including accelerated growth in childhood ...
Aldosterone normally functions to increase sodium retention (which brings water as well) in exchange for potassium. Thus, lack of aldosterone causes hyperkalemia and hyponatremia. In fact, this is a distinguishing point from 11-hydroxylase deficiency, in which one of the increased products is 11-deoxycorticosterone that has weak ...