Meta-Biol

• Pathways

25-hydroxycholesterol 7-alpha-hydroxylase (CYP7B1) normally 7alpha-hydroxylates 25-hydroxycholesterol (25OH-CHOL) to cholest-5-ene-3beta,7alpha,25-triol (CHOL3b,7a,25TRIOL). Defects in CYP7B1 can cause spastic paraplegia 5A, autosomal recessive (SPG5A; MIM:270800), a neurodegenerative disorder characterised by a slow, gradual, progressive weakness and spasticity of the lower limbs (Tsaousidou et al. 2008). Mutations causing SPG5A include S363F, G57R, R417H, F216S, Y275*, F470I, G87V and T297A (Tsaousidou et al. 2008, Schule et al. 2009, Goizet et al. 2009, Arnoldi et al. 2012). Defects in CYP7B1 can also cause congenital bile acid synthesis defect 3 (CBAS3; MIM:613812), a disorder resulting in severe cholestasis, cirrhosis and liver synthetic failure. Hepatic CYP7B1 activity is undetectable (Setchell et al. 1998). A mutation causing CBAS3 is R388* (Setchell et al. 1998).