- Volume 40 Issue 6
DOI QR Code
Construction and Expression of Mutant cDNAs Responsible for Genetic Polymorphism in Aldehyde Oxidase in Donryu Strain Rats
- Adachi, Mayuko (Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University) ;
- Itoh, Kunio (Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University) ;
- Masubuchi, Akiko (Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University) ;
- Watanabe, Nobuaki (Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi-Sankyo Co. Ltd.) ;
- Tanaka, Yorihisa (Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University)
- Published : 2007.11.30
We demonstrated the genetic polymorphism of aldehyde oxidase (AO) in Donryu strain rats: the ultrarapid metabolizer (UM) with nucleotide mutation of (377G, 2604C) coding for amino acid substitution of (110Gly, 852Val), extensive metabolizer (EM) with (377G/A, 2604C/T) coding for (110Gly/Ser, 852Val/Ala), and poor metabolizer (PM) with (377A, 2604T) coding for (110Ser, 852Ala), respectively. The results suggested that 377G > A and/or 2604C > T should be responsible for the genetic polymorphism. In this study, we constructed an E. coli expression system of four types of AO cDNA including Mut-1 with (377G, 2604T) and Mut-2 with (377A, 2604C) as well as naturally existing nucleotide sequences of UM and PM in order to clarify which one is responsible for the polymorphism. Mut-1 and Mut-2 showed almost the same high and low activity as that of the UM and PM groups, respectively. Thus, the expression study of mutant AO cDNA directly revealed that the nucleotide substitution of 377G > A, but not that of 2604C > T, will play a critical role in the genetic polymorphism of AO in Donryu strain rats. The reason amino acid substitution will cause genetic polymorphism in AO activity was discussed.
- Beedham, C. (1985) Molybdenum hydroxylases as drug-metabolizing enzymes. Drug Metab. Rev. 16, 119-156. https://doi.org/10.3109/03602538508991432
- Beedham, C. (1987) Molybdenum hydroxylases: Biological distribution and substrate-inhibitor specificity. Prog. Med. Chem. 24, 85-121. https://doi.org/10.1016/S0079-6468(08)70420-X
- Beedham, C. (1997) The role of non-P450 enzymes in drug oxidation. Pharm. World Sci. 19, 255-263. https://doi.org/10.1023/A:1008668913093
- Beedham, C. (1998) Molybdenum hydroxylases; in Metabolism of Xenobiotics, Gorrod, J. W., Oeschlager, H., and Caldwell, J. (eds), pp. 51-58, Taylor and Francis, London and New York, USA.
- Beedham, C. (2002) Molybdenum hydroxylase; in Enzyme Systems that Metabolise Drug and Other Xenobiotics, Ioannides, C. (ed.), pp. 147-187, John Wiley, Chichester, UK.
- Beedham, C., Miceli, J. J. and Obach, S. (2003) Ziprasidone metabolism, aldehyde oxidase, and clinical implications. J. Clin. Psychopharm. 23, 229-232. https://doi.org/10.1097/00004714-200306000-00003
- Glueksohn-Waelsch, S., Greengard, P., Quinn, G. P. and Teicher, L. S. (1967) Genetic variations of an oxidase in mammals. J. Biol. Chem. 242, 1271-1273.
- Huang, D. Y., Furukawa, A. and Ichikawa, Y. (1999) Molecular cloning of retinal oxidase/aldehyde oxidase cDNA from rabbit and mouse liver and functional expression of recombinant mouse retinal oxidase cDNA in Escherichia coli. Arch Biochem. Biophys. 364, 264-272. https://doi.org/10.1006/abbi.1999.1129
- Itoh, K., Yamamura, M., Muramatsu, S., Hoshino, K., Masubuchi, A., Sasaki, T. and Tanaka, Y. (2005) Stereospecific oxidation of (S)-enantiomer of RS-8359, a selective and reversible MAO-A inhibitor, by aldehyde oxidase. Xenobiotica 35, 561-573. https://doi.org/10.1080/00498250500202106
- Itoh, K., Yamamura, M., Takasaki, W., Sasaki, T., Masubuchi, A. and Tanaka, Y. (2006) Species differences in enantioselective 2-oxidation of RS-8359, a selective and reversible MAO-A inhibitor, and cinchona alkaloids by aldehyde oxidase. Biopharm. Drug Dispos. 27, 1133-1139.
- Itoh, K., Masubuchi, A., Sasaki, T., Adachi, M., Watanabe, N., Nagata, K., Yamazoe, Y., Hiratsuka, M., Mizugaki, M. and Tanaka, Y. (2007) Polymorphism of aldehyde oxidase in Donryu rats. Drug Metab. Dispos. 35, 734-739. https://doi.org/10.1124/dmd.106.011502
- Iwata, N., Tonohiro, T., Kozuka, M., Kumagae, Y., Takasaki, W. and Tanaka, Y. (1996) A novel selective and reversible MAO-A inhibitor, RS-8359: its pharmacological properties and metabolism. Int. Acad. Biomed. Drug Res. 11, 285-286.
- Jordan, C. G. M., Rashidi, M. R., Laljee, H., Clarke, S. E., Brown, J. E. and Beedham, C. (1999) Aldehyde oxidase-catalyzed oxidation of methotrexate in the liver of guinea pig, rabbit and man. J. Pharm. Pharmacol. 51, 411-418. https://doi.org/10.1211/0022357991772619
- Kitamura, S., Sugihara, K., Nakatani, K., Ohta, S., O'Hara, T., Nimomiya, S., Green, C. E. and Tyson, C. A. (1999a) Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans. IUBMB Life. 48, 607-611. https://doi.org/10.1080/713803569
- Kitamura, S., Nakatani, K., Sugihara, K., and Ohta, S. (1999b) Strain differences of the ability to hydroxylate methotrexate in rats. Com. Biochem. Phys. Part C 122, 331-336. https://doi.org/10.1016/S1095-6433(99)00014-8
- Kitamura, S., Sugihara, K. and Ohta, S. (2006) Drug-metabolizing ability of molybdenum hydroxylases. Drug Metab. Pharmacokinet. 21, 83-98. https://doi.org/10.2133/dmpk.21.83
- Kumagae, Y., Matsui, Y. and Iwata, N. (1991) Deamination of norepinephrine, dopamine, and serotonin by type A monoamine oxidase in discrete regions of the rat brain and inhibition by RS-8359. Jpn. J. Pharmacol. 55, 121-128. https://doi.org/10.1254/jjp.55.121
- Miura, H., Naoi, M., Nakahara, D., Ohta, T. and Nagatsu, T. (1993) Changes in monoamine levels in mouse brain elicited by forcedswimming stress, and the protective effect of a new monoamine oxidase inhibitor, RS-8359. J. Neural Transm. 94, 175-187. https://doi.org/10.1007/BF01277023
- Plenker, A., Puchler, K. and Volz, H. P. (1997) The effects of RS- 8359 on cardiovascular function in healthy subjects and depressed patients. Int. Clin. Psychopharm. 12, S25-S29.
- Prakash, C., Kamel, A., Gummerus, J. and Wilner, K. (1997) Metabolism and excretion of a new antipsychotic drug, ziprasidone, in humans. Drug Metab. Dispos. 25, 863-875.
- Puchler, K., Schaffler, K. and Plenker, A. (1997) The comparative effects of single and multiple doses of RS-8359, moclobemide and placebo on psychomotor function in healthy subjects. Int. Clin. Psychopharm. 12, 17-23.
- Rashidi, M. R., Smith, J. A., Clarke, S. E. and Beedham, C. (1997) In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit and rat liver. Drug Metab. Dispos. 25, 805-813.
- Sasaki, T., Masubuchi, A., Yamamura, M., Watanabe, N., Hiratsuka, M., Mizugaki, M., Itoh, K. and Tanaka, Y. (2006) Rat strain differences in stereospecific 2-oxidation of RS-8359, a reversible and selective MAO-A inhibitor, by aldehyde oxidase. Biopharm. Drug Dispos. 27, 247-255. https://doi.org/10.1002/bdd.504
- Sugihara, K., Kitamura, S. and Tatsumi, K. (1995) Strain differences of liver aldehyde oxidase in rats. Biochem. Mol. Biol. Int. 37, 861-869.
- Takasaki, W., Yamamura, M., Nozaki, A., Nitanai, T., Sasahara, K., Itoh, K. and Tanaka, Y. (2005) Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug metabolizing enzymes. Chirality 17, 135-141. https://doi.org/10.1002/chir.20124
- Wright, R. M., Clayton, D. A., Riley, M. G., McManaman, J. L. and Repine, J. E. (1999) cDNA cloning, sequencing, and characterization of male and female rat liver aldehyde oxidase (rAOX1). J. Biol. Chem. 274, 3878-3886. https://doi.org/10.1074/jbc.274.6.3878
- Yamaguchi, Y., Matsumura, T., Ichida, K., Okamoto, K. and Nishino, T. (2007) Human xanthine oxidase changes its substrate specificity to aldehyde oxidase type upon mutation of amino acid residues in the active site: role of active site residues in binding and activation of purine substrate. J. Biochem. 141, 513-524. https://doi.org/10.1093/jb/mvm053
- Yokoyama, T., Karube, T. and Iwata, N. (1989) Comparative studies of the effects of RS-8359 and safrazine on monoamine oxidase in vitro and in vivo in mouse brain. J. Pharm. Pharmacol. 41, 32-36. https://doi.org/10.1111/j.2042-7158.1989.tb06324.x
- Optimization of the Expression of Human Aldehyde Oxidase for Investigations of Single-Nucleotide Polymorphisms vol.44, pp.8, 2016, https://doi.org/10.1124/dmd.115.068395
- Functional Analysis of Aldehyde Oxidase Using Expressed Chimeric Enzyme between Monkey and Rat vol.32, pp.1, 2009, https://doi.org/10.1248/bpb.32.31
- Structure and function of mammalian aldehyde oxidases vol.90, pp.4, 2016, https://doi.org/10.1007/s00204-016-1683-1
- In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor vol.11, pp.1, 2011, https://doi.org/10.1038/tpj.2010.8
- Individual and Strain Difference of Aldehyde Oxidase in Rat vol.129, pp.12, 2009, https://doi.org/10.1248/yakushi.129.1487
- The role of aldehyde oxidase in drug metabolism vol.8, pp.4, 2012, https://doi.org/10.1517/17425255.2012.663352