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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 ...
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. [citation needed]
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.
It spontaneously and reversibly converts to various less polar forms and derivatives, some of which serve as precursors to aldosterone or corticosterone. Specifically, 21-hydroxy-11,18-oxido-4-pregnene-3,20-dione (18-DAL) is hydroxylated to aldosterone in the presence of malate and NADP+ at pH 4.8, indicating that 18-DAL acts as a metabolic ...
Lorundrostat (developmental name MLS 101) is an aldosterone synthase inhibitor developed by Mineralys Therapeutics for high blood pressure. In clinical trials as an add-on medication for people with uncontrolled hypertension, decreased renin and elevated aldosterone it significantly reduced blood pressure. Hyperkalemia occurred in some trial ...
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 .
The enzyme aldosterone synthase (also known as CYP11B2) acts in this location [3] [4] The expression of neuron-specific proteins in the zona glomerulosa cells of human adrenocortical tissues has been predicted and reported by several authors [5] [6] [7] and it was suggested that the expression of proteins like the neuronal cell adhesion ...