Cholesterol 24-hydroxylase

Cholesterol 24-hydroxylase
Structure of cholesterol 24-hydroxylase (CYP46A1) in Homo sapiens. Based on PyMOL rendering of PDB 2Q9F.
Identifiers
EC no.1.14.13.98
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Cholesterol 24-hydroxylase (EC 1.14.13.98), also commonly known as cholesterol 24S-hydroxylase, cholesterol 24-monooxygenase, CYP46, or CYP46A1, is an enzyme that catalyzes the conversion of cholesterol to 24S-hydroxycholesterol. It is responsible for the majority of cholesterol turnover in the human central nervous system. The systematic name of this enzyme class is cholesterol,NADPH:oxygen oxidoreductase (24-hydroxylating).

This enzyme is a member of the cytochrome P450 (CYP) superfamily of enzymes. Like many other CYP enzymes that act on cholesterol, cholesterol-24 hydroxylase is a monooxygenase that hydroxylates the side-chain of cholesterol.

Because 24S-hydroxycholesterol is more polar than cholesterol, it can more easily pass the blood–brain barrier to exit the brain and pass into the bloodstream, where it can then travel to the liver to be further degraded. This enzyme has also been found at low quantities in the retina, where it performs the same function to a lesser degree.

Genetic cloning of the encoding gene (CYP46A1) was first accomplished in 1999 and an extensive E. coli expression and purification system was later developed in 2003.