CYP7B1

CYP7B1 is a human gene encoding the enzyme cytochrome P450, family 7, subfamily B, polypeptide 1, commonly referred to as oxysterol 7-alpha-hydroxylase. This enzyme is a member of the cytochrome P450 superfamily, a group of monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.

The CYP7B1 enzyme catalyzes the 7-alpha-hydroxylation of several oxysterols, including 25-hydroxycholesterol, 27-hydroxycholesterol, and 5-beta-cholestane-3-alpha,7-alpha-diol. These hydroxylation reactions are important steps in the bile acid synthesis pathway, specifically the alternative, or acidic, pathway. Bile acids are synthesized in the liver and play a crucial role in the absorption of fats and fat-soluble vitamins in the intestine.

Mutations in the CYP7B1 gene can lead to several human diseases. These include:

• Congenital bile acid synthesis defect type 3 (CBAS3): This autosomal recessive disorder results from a deficiency in oxysterol 7-alpha-hydroxylase, leading to abnormal bile acid synthesis and cholestasis. This can manifest as neonatal liver disease and potentially progress to cirrhosis.

• Spastic paraplegia 5A, autosomal recessive (SPG5A): While the exact mechanism is still being investigated, mutations in CYP7B1 have been linked to this form of hereditary spastic paraplegia. SPG5A is characterized by progressive lower limb spasticity and weakness.

The CYP7B1 gene is primarily expressed in the liver, but also found in other tissues including the brain. Research suggests it plays a role in the metabolism of steroids and other lipids within the central nervous system, potentially contributing to neurological functions and the development of neurodegenerative diseases.