Cytochrome P450 2U1 (CYP2U1)

Cytochrome P450 2U1 (CYP2U1) is a distinctive member of the cytochrome P450 superfamily of heme-thiolate monooxygenases, characterized by its primary expression in the brain and thymus. CYP2U1 catalyzes the omega and omega-1 hydroxylation of long-chain fatty acids such as arachidonic acid and docosahexaenoic acid, thereby producing metabolites like 20-HETE, 22-hydroxy-docosahexaenoic acid, and others that regulate vascular tone, inflammation, and central nervous system function. CYP2U1 also metabolizes N-arachidonoylserotonin, influencing the endocannabinoid system and nociception. Mutations in the CYP2U1 gene are causative in hereditary spastic paraplegia (SPG49/SPG56), a neurodegenerative disorder with progressive lower limb spasticity. Although no direct therapeutics currently target CYP2U1, its functional importance in lipid signaling and neurodegeneration makes it a gene of emerging translational research interest.

Other names

Cytochrome P450 family 2 subfamily U member 1CYP2U1SPG49Spastic paraplegia 49Long-chain fatty acid omega-monooxygenaseP450TECSpastic paraplegia 56 (autosomal dominant)

Enzymatic oxidation (hydroxylation) of fatty acids at the omega or omega-1 position. Metabolic inactivation of N-arachidonoylserotonin, thus modulating anti-nociceptive and endocannabinoid pathways.