Systematic identification and characterization of essential drug-metabolizing enzyme toward establishment of platform for drug metabolism research in veterinary species

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Kagoshima University
• Principal Investigator: Uno Yasuhiro 鹿児島大学, 農水産獣医学域獣医学系, 准教授 (90372276)
• Co-Investigator(Kenkyū-buntansha): 山崎 浩史 昭和薬科大学, 薬学部, 教授 (30191274)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 薬物代謝酵素 / 獣医動物種 / ゲノム / 遺伝子

Outline of Final Research Achievements

In humans, various drug-metabolizing enzymes are important for drug metabolism, and differences in their enzyme function and tissue expression account for sex, age, individual, and racial differences in drug efficacy and toxicity. However, in most animal species, the major enzymes have not been identified, making it difficult to understand drug metabolism. In this study, we identified major drug-metabolizing enzymes such as cytochromes P450 (CYPs) in animal species such as dogs, pigs, and cats, and analyzed their tissue expressions and functions. As a result, many CYP isoforms showed gene and genome structures, tissue expression patterns, and metabolic functions similar to the corresponding human CYPs, but some differences in tissue expression and metabolic functions were also observed.

Free Research Field

薬物代謝学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

ヒトと異なり多くの動物種では主要な酵素が同定されておらず薬物代謝の理解が進まなかったが、本研究でイヌやブタ、ネコ等の動物種についてチトクロムP450（CYP）を始めとする重要な薬物代謝酵素を同定し解析したことにより、これらの動物種で薬物代謝の理解が大いに進んだ。この解析により得られた知見は、これらの動物種で医薬品開発や薬物治療を行う上で重要な研究基盤となるものと期待される。