Cytochrome P450 family 4 subfamily A member 11 (CYP4A11)

Cytochrome P450 family 4 subfamily A member 11 (CYP4A11) is a microsomal heme-thiolate enzyme primarily expressed in the liver and kidney, where it functions as a fatty acid omega-hydroxylase (NCBI Gene, Wikipedia). It is the principal human enzyme responsible for the omega-oxidation of medium- and long-chain fatty acids, as well as the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE) (PubMed, PMC). 20-HETE is a potent lipid mediator that regulates vascular tone, renal sodium transport, and blood pressure homeostasis (PubMed). Dysregulation of CYP4A11 activity or expression is implicated in several diseases, including essential hypertension, metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD), and various cancers such as lung and colorectal cancer (PubMed, MDPI). Genetic polymorphisms in the CYP4A11 gene, notably the rs1126742 (T8590C) variant, are associated with an increased risk of hypertension and ischemic stroke due to reduced 20-HETE production (NCBI Gene, Wikipedia). Therapeutic interest in CYP4A11 focuses on the development of selective inhibitors to manage hypertension and inflammation, as well as its potential as a biomarker for metabolic and cardiovascular health (PubMed). While the target name provided (CYP4A1) refers to the rat ortholog, CYP4A11 is the relevant human therapeutic target (UniProt, NCBI Gene).

Other names

Cytochrome P450 4A11CP4YCYP4A2CYP4AII20-HETE synthaseFatty acid omega-hydroxylaseLauric acid omega-hydroxylaseCytochrome P450 4A1 (rat ortholog)

CYP4A11 is targeted primarily through the inhibition of 20-HETE synthesis, which reduces 20-HETE-mediated vasoconstriction and pro-inflammatory signaling via the GPR75 receptor (PubMed). Alternatively, induction of CYP4A11 by PPAR-alpha agonists like fibrates enhances the omega-oxidation of fatty acids, facilitating their clearance and reducing lipotoxicity in metabolic diseases (PMC).