CYP11B2

CYP11B2 is the gene encoding aldosterone synthase, a mitochondrial cytochrome P450 enzyme expressed mainly in the zona glomerulosa of the adrenal cortex. It is responsible for the final steps of aldosterone biosynthesis, acting on precursors such as 11-deoxycorticosterone and related steroids to produce aldosterone, the principal mineralocorticoid involved in salt and water balance.

The enzyme catalyzes three sequential reactions: 11β-hydroxylation, followed by 18-hydroxylation and 18-oxidation. These transformations convert the precursors into aldosterone, with the reactions dependent on mitochondrial electron transfer from NADPH via P450 oxidoreductase. The activity of CYP11B2 is spatially restricted to adrenal zona glomerulosa cells and is coordinated with the organism’s electrolyte status and blood pressure.

Regulation of CYP11B2 expression and aldosterone production is primarily driven by angiotensin II and plasma potassium levels, which stimulate transcription and enzymatic activity to increase aldosterone synthesis. ACTH can play a permissive role but is not the principal regulator under normal physiological conditions.

Genetic and clinical significance: CYP11B2 is central to aldosterone homeostasis. Increased activity or expression can contribute to primary hyperaldosteronism, presenting with hypertension and hypokalemia. A notable genetic alteration is a chimeric CYP11B1/CYP11B2 gene, which causes glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type I) due to ACTH-regulated ectopic aldosterone production. Conversely, reduced CYP11B2 function can impair aldosterone synthesis, affecting fluid and electrolyte balance. CYP11B2 remains a key focus in research on adrenal steroidogenesis and disorders of mineralocorticoid excess.