aldosterone biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of aldosterone, a corticosteroid hormone that is produced by the zona glomerulosa of the adrenal cortex and regulates salt (sodium and potassium) and water balance. [PMID:16527843]

The aldosterone biosynthetic process is a complex cascade of enzymatic reactions that occur primarily in the zona glomerulosa of the adrenal cortex. It begins with the precursor molecule cholesterol, which is transported into the mitochondria of adrenal cells. Within the mitochondria, cholesterol undergoes a series of enzymatic transformations catalyzed by the enzyme CYP11A1 (also known as P450scc), leading to the formation of pregnenolone. Pregnenolone is then transported out of the mitochondria and enters the endoplasmic reticulum, where it undergoes further enzymatic modifications.

The first step in the endoplasmic reticulum is the conversion of pregnenolone to progesterone by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD). Progesterone is then converted to 11-deoxycorticosterone (DOC) by the enzyme 21-hydroxylase (CYP21A2). DOC is then hydroxylated at the 11β position by the enzyme 11β-hydroxylase (CYP11B1) to form corticosterone.

Corticosterone is the primary precursor for aldosterone biosynthesis. It is then transported back into the mitochondria, where it undergoes the final two steps in the aldosterone biosynthetic pathway. The enzyme aldosterone synthase (CYP11B2) catalyzes the conversion of corticosterone to 18-hydroxycorticosterone, followed by the conversion of 18-hydroxycorticosterone to aldosterone.

The entire aldosterone biosynthetic process is tightly regulated by various factors, including the renin-angiotensin-aldosterone system (RAAS), potassium levels, and ACTH. The RAAS is the primary regulator of aldosterone synthesis, and it involves a cascade of events that ultimately lead to the release of aldosterone from the adrenal glands. When blood pressure falls, the kidneys release renin, which activates the RAAS. This results in the production of angiotensin II, a powerful vasoconstrictor that also stimulates aldosterone secretion.

Aldosterone is a mineralocorticoid hormone that plays a crucial role in maintaining sodium and potassium balance in the body. It acts on the distal tubules of the kidneys, promoting sodium reabsorption and potassium excretion. This helps to regulate blood pressure, blood volume, and electrolyte balance.

Mutations or deficiencies in the enzymes involved in aldosterone biosynthesis can lead to various disorders, including primary aldosteronism (Conn's syndrome), Addison's disease, and 11β-hydroxylase deficiency. These disorders can manifest with symptoms such as hypertension, hypokalemia, and electrolyte imbalances.'
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Proteins (3)

Compounds (33)