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Concept
Steroid 11β-hydroxylase
Summary
Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. The enzyme is involved in the biosynthesis of adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions.
The CYP11B1 gene encodes 11β-hydroxylase - a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The product of this CYP11B1 gene is the 11β-hydroxylase protein. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of various steroids in the adrenal cortex. Transcript variants encoding different isoforms have been noted for this gene.
The CYP11B1 gene is reversibly inhibited by etomidate and metyrapone.
11β-hydroxylase is a steroidogenic enzyme, i.e. the enzyme involved in the metabolism of steroids.
Humans have two isozymes with 11β-hydroxylase activity: CYP11B1 and CYP11B2.
CYP11B1 (11β-hydroxylase) is expressed at high levels and is regulated by ACTH, while CYP11B2 (aldosterone synthase) is usually expressed at low levels and is regulated by angiotensin II. In addition to the 11β-hydroxylase activity, both isozymes have 18-hydroxylase activity. The CYP11B1 isozyme has strong 11β-hydroxylase activity, but the activity of 18-hydroxylase is only one-tenth of CYP11B2. The weak 18-hydroxylase activity of CYP11B1 explains why an adrenal with suppressed CYP11B2 expression continues to synthesize 18-hydroxycorticosterone.
Here are some of the steroids, grouped by catalytic activity of the CYP11B1 isozyme:
strong activity:
11-deoxycortisol to cortisol,
11-deoxycorticosterone to corticosterone;
medium activity:
progesterone to 11β-hydroxyprogesterone,
17α-hydroxyprogesterone to 21-deoxycortisol,
androstenedione to 11β-hydroxyandrostenedione;
testosterone to 11β-hydroxytestosterone,
weak activity:
corticosterone to 18-hydroxycorticosterone,
cortisol to 18-hydroxycortisol.
Official source
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