Aldosterone synthase

Aldosterone synthase is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone. It is also known by its systematic name, steroid 18-hydroxylase, and is encoded by the CYP11B2 gene in humans. Aldosterone synthase plays a crucial role in the renin-angiotensin system (RAS), influencing blood pressure regulation and electrolyte balance.

Function

Aldosterone synthase catalyzes the final step in the production of aldosterone, converting corticosterone to aldosterone in the adrenal cortex. This process involves three main reactions: hydroxylation at the 18th carbon, oxidation of the 18-hydroxyl to an aldehyde, and finally, hydroxylation at the 11β position. The enzyme is found exclusively in the zona glomerulosa of the adrenal cortex, distinguishing it from the closely related enzyme, 11β-hydroxylase, which is involved in cortisol synthesis and is expressed in the zona fasciculata.

Genetics

The CYP11B2 gene is located on chromosome 8q22 and consists of nine exons. Genetic variations in CYP11B2 can affect aldosterone synthase activity, influencing aldosterone production and, consequently, blood pressure levels and electrolyte balance. Mutations in this gene have been associated with aldosterone synthase deficiency, a condition characterized by salt wasting and failure to thrive in infancy.

Clinical Significance

Aldosterone plays a key role in regulating blood pressure through sodium retention and potassium excretion. Overproduction of aldosterone, due to conditions such as Conn's syndrome (primary hyperaldosteronism), can lead to hypertension and hypokalemia. Conversely, inadequate aldosterone production can result in Addison's disease, characterized by hypotension and hyperkalemia.

Inhibitors of aldosterone synthase are being explored as potential treatments for conditions associated with excessive aldosterone production, such as hypertension and heart failure. These inhibitors could offer a targeted approach to modulate the effects of aldosterone, providing benefits over traditional treatments that affect broader pathways in the renin-angiotensin system.

See Also

• CYP450
• Mineralocorticoid
• Renin-angiotensin system
• Adrenal cortex
• Hypertension

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