Genetic diversity of cytochrome P450 2A with different metabolic activities in domestic cats

• Published in: Journal of Veterinary Medical Science Vol. 81; no. 7; pp. 983 - 985
• Main Authors: SUGIYAMA, Souta, UNO, Yasuhiro, AMANO, Tomoko, KITAZAWA, Takio, TERAOKA, Hiroki
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 01.07.2019; Japan Science and Technology Agency; The Japanese Society of Veterinary Science
• Subjects: Animals; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Cats; Cats - genetics; Cats - metabolism; Coumarin; Coumarins - metabolism; Cytochrome; Cytochrome P450; domestic cat; Female; Genetic diversity; Genetic Variation; Hydroxylation; Isoforms; Liver - enzymology; Lungs; Male; Metabolism; polymorphism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Sequence Analysis, DNA; Steroid Hydroxylases - genetics; Steroid Hydroxylases - metabolism; Toxicology; xenobiotic; domestic cat; polymorphism; cytochrome P450; xenobiotic
• ISSN: 0916-7250; 1347-7439
• DOI: 10.1292/jvms.19-0107

Knowledge of genetic polymorphisms of cytochrome P450 (CYP), the most important xenobiotic metabolizing enzyme, is very limited in cats. Preliminarily, we investigated genetic polymorphisms in CYP2A13, one of the major CYP isoforms in the liver and lung. Four synonymous and three non-synonymous polymorphic variants were identified in feline CYP2A13 in domestic cats in Japan, without an obvious major type. Metabolic parameters, Km and Vmax, of coumarin hydroxylation of CYP2A13 were shown to range within two times for the identified non-synonymous polymorphic variants by using heterologous coexpression system in Escherichia coli. The results confirmed the polymorphic nature of CYP2A13 as a basis for effective application of medicines and prevention of adverse reactions in treatment of domestic cats.