Hydroxylation

Hydroxylation is a chemical process that introduces a hydroxyl group (-OH) into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air. It is extremely important in detoxification since hydroxylation converts lipophilic compounds into water-soluble (hydrophilic) products that are more readily excreted. Some drugs (e.g. steroids) are activated or deactivated by hydroxylation.

Chemical concepts

The hydroxylation process involves conversion of a CH group into a COH group. Hydroxylation is an oxidative process. The oxygen that is inserted into the C-H bond is usually derived from atmospheric oxygen (O2). Since O2 itself is a slow hydroxylating agent, catalysts are required to accelerate the pace of the process.

Biological hydroxylation

The principal hydroxylation agent in nature is cytochrome P-450, hundreds of variations of which are known. Other hydroxylating agents include flavins.

Aldosterone synthase

Aldosterone synthase is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone. It is a protein which is only expressed in the zona glomerulosa of the adrenal cortex and is primarily regulated by the renin-angiotensin system. It is the sole enzyme capable of synthesizing aldosterone in humans and plays an important role in electrolyte balance and blood pressure.

Genetics

Aldosterone synthase is encoded on chromosome 8q22 by the CYP11B2 gene. The gene contains 9 exons and spans roughly 7000 base pairs of DNA. CYP11B2 is closely related with CYP11B1. The two genes show 93% homology to each other and are both encodes on the same chromosome. Research has shown that calcium ions act as a transcription factor for CYP11B2 through well defined interactions at the 5'-flanking region of CYP11B2.

Aldosterone synthase is 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.