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Cytochrome P450-Dependent Change in UDP-Glucuronosyltransferase Function and Its Reverse Regulation

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Fifty Years of Cytochrome P450 Research

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Abstract

Cytochrome P450 (P450, CYP) and UDP-glucuronosyltransferase (UGT) are important enzymes involved in phase I and II drug metabolism, respectively. It has long been believed that these enzymes work separately, because their topology with regard to the endoplasmic reticulum membrane is very different and the location of the two enzymes is separated by the membrane. However, cumulative evidence suggests that these enzymes interact with each other to modify their respective functions. This review mainly focuses on a P450-dependent alteration in UGT function and discusses the relevance of this modification to the polymorphic nature of drug metabolism mediated by UGTs. Also, we describe the selectivity of P450/UGT isoforms in terms of their pairing and possible P450/UGT domains serving the interactions. The reverse modulation, that is, the alteration of P450 function by UGT, is also described.

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Acknowledgments

The studies carried out in our laboratory were supported in part by Grants in Aids from the Ministry of Technology, Education, Science, and Sports or the Japanese Society for the Promotion of Science. The authors thank collaborators Dr. Mackenzie in Flinders University, Dr. Nagata in Tohoku Pharmaceutical University, Dr. Yamazoe in the Graduate School of Pharmaceutical Sciences, Tohoku University (present address: Cabinet Office, Government of Japan), Dr. Ikushiro in Toyama Prefectural University, Dr. Taketomi in Hokkaido University School of Medicine, and Dr. Maehara in the Graduate School of Medical Science, Kyushu University. The authors are also very grateful to their former mentor and professor emeritus, the late Dr. Oguri. They also thank all the staff and graduate and undergraduate students in the Laboratory of Molecular Life Sciences, Kyushu University who were involved in the study.

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  1. Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

    Yuji Ishii, Yuu Miyauchi & Hideyuki Yamada

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  1. Yuji Ishii
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  2. Yuu Miyauchi
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  3. Hideyuki Yamada
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Correspondence to Yuji Ishii .

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  1. Showa Pharmaceutical University, Tokyo, Japan

    Hiroshi Yamazaki

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Ishii, Y., Miyauchi, Y., Yamada, H. (2014). Cytochrome P450-Dependent Change in UDP-Glucuronosyltransferase Function and Its Reverse Regulation. In: Yamazaki, H. (eds) Fifty Years of Cytochrome P450 Research. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54992-5_18

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