CYP46 Background Information
Cytochrome P450 proteins are heme-thiolate monooxygenases that mediate NADPH-dependent electron transport and function to oxidize a variety of structurally unrelated compounds, including steroids, fatty acids and xenobiotics. Specifically, Cytochrome P450s are responsible for metabolizing arachidonic acid to hydroxyeicosatetraenoic acid (a regulator of blood pressure) and epoxyeicosatrienoic acid (a molecule involved in signaling events). CYP46, also known as CYP46A1 (cytochrome P450, family 46, subfamily A, polypeptide 1) or CP46, is a 500 amino acid protein that localizes to the endoplasmic reticulum and shares 95% sequence identity with its mouse counterpart. Expressed predominately in brain tissue, CYP46 catalyzes the conversion of cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol, thereby playing an important role in cholesterol homeostasis and turnover. Variations in the gene encoding CYP46 that influence brain cholesterol metabolism are associated with an increased risk for Alzheimer's disease (AD).