Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum.
- Natalia Mast,
- Kyle W Anderson,
- Joseph B Lin,
- Yong Li,
- Illarion V Turko,
- Curtis Tatsuoka,
- Ingemar Bjorkhem,
- Irina A Pikuleva
J Biol Chem 2017 Feb 11. Epub 2017 Feb 11.
Case Western Reserve University, United States;
Cytochrome P450 27A1 (CYP27A1 or sterol 27-hydroxylase) is a ubiquitous, multifunctional enzyme catalyzing regio- and stereo-specific hydroxylation of different sterols. In humans, complete CYP27A1 deficiency leads to cerebrotendinous xanthomatosis or nodule formation in tendons and brain (preferentially in the cerebellum) rich in cholesterol and cholestanol, the 5α-saturated analog of cholesterol. In Cyp27a1(-/-) mice, xanthomas are not formed, despite a significant cholestanol increase in the brain and cerebellum. Read More