CYP8B1

CYP8B1 is a gene that encodes a cytochrome P450 enzyme, specifically lanosterol 14α-demethylase, also known as sterol 12α-hydroxylase. This enzyme plays a crucial role in bile acid biosynthesis in the liver.

The CYP8B1 enzyme catalyzes the 12α-hydroxylation of 5β-cholest-7-en-3α-ol and 5β-cholestanol. This is a key regulatory step directing the synthesis of cholic acid, one of the two primary bile acids in humans. The other primary bile acid is chenodeoxycholic acid, and the ratio of cholic acid to chenodeoxycholic acid is significantly influenced by the activity of CYP8B1.

Deficiency in CYP8B1 is a rare autosomal recessive disorder. Individuals with CYP8B1 deficiency typically exhibit symptoms such as cholestasis, hyperbilirubinemia, and fat malabsorption. This is due to the impaired production of cholic acid, which is essential for the emulsification and absorption of fats in the small intestine. The impaired bile acid pool can lead to liver damage and progressive cholestatic liver disease. Diagnosis of CYP8B1 deficiency often involves bile acid analysis and genetic testing to identify mutations in the CYP8B1 gene. Treatment options may include supplementation with cholic acid to restore the bile acid pool and improve fat absorption.

The gene itself is primarily expressed in the liver. Its expression is regulated by various factors, including bile acids themselves, providing feedback control over bile acid synthesis. Research continues to explore the complex regulation of CYP8B1 and its role in maintaining bile acid homeostasis.