title: Cynomolgus macaque CYP4 isoforms are functional, metabolizing arachidonic acid.
abstract: Cytochrome P450 (CYP) is important for metabolism of not only xenobiotics such as drugs, but also endogenous compounds including arachidonic acids. CYP4A11, CYP4F3v2, CYP4F11, and CYP4F45 have been identified in cynomolgus macaque, an animal species widely used for investigation of drug metabolism due to its evolutionary closeness to human. However, their metabolic functions have not been investigated. In this study, proteins were heterologously expressed in Escherichia coli and characterized by metabolic assays using arachidonic acids as substrates that are metabolized by CYP4 isoforms in human. The results showed that all four CYPs metabolized arachidonic acids. Therefore, cynomolgus macaque CYP4A11, CYP4F3v2, CYP4F11, and CYP4F45 are functional enzymes.
authors.affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Kainan, Wakayama 642–0017, Japan. uno-yasuhiro@snbl.co.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Matsuno
authors.forename: Chika
authors.initials: C
authors.lastname: Nakamura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Utoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D042926:Cytochrome P-450 CYP4A / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008252:Macaca fascicularis / Q000378:metabolism*; D010802:Phylogeny; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D016718:Arachidonic Acid; D042926:Cytochrome P-450 CYP4A