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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
Progesterone is the entry into the Δ 4 pathway, resulting in production of 17α-hydroxyprogesterone and androstenedione, precursor to testosterone and estrone. Aldosterone and corticosteroids are also derived from progesterone or its derivatives. Pregnenolone can be converted to 17α-hydroxypregnenolone by the enzyme 17α-hydroxylase .
It selectively stimulates secretion of aldosterone. The secretion of aldosterone has a diurnal rhythm. Control of aldosterone release from the adrenal cortex: [citation needed] The role of the renin–angiotensin system: Angiotensin is involved in regulating aldosterone and is the core regulator. Angiotensin II acts synergistically with potassium.
Corticosterone has only weak glucocorticoid and mineralocorticoid potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone. Corticosterone is converted to aldosterone by aldosterone synthase , found only in the mitochondria of glomerulosa cells.
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).
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. Steroidogenesis, showing aldosterone synthesis at upper-right corner. [13] Aldosterone synthase is normally absent in other sections of the adrenal gland. [14]
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]