In Vitro Study of 6-mercaptopurine Oxidation Catalysed by Aldehyde Oxidase and Xanthine Oxidase
作者： Mohammad-Reza Rashidi , Christine Beedham , John S. Smith , Soodabeh Davaran
DOI: 10.2133/DMPK.22.299
关键词:
摘要: Summary: In spite of over 40 years clinical use 6-mercaptopurine, many aspects complex pharmacology and metabolism this drug remain unclear. It is thought that 6-mercaptopurine oxidized to 6-thiouric acid through 6-thioxanthine or 8-oxo-6-mercaptopurine by one two molybdenum hydroxylases, xanthine oxidase (XO), however, the role other hydroxylase, aldehyde (AO), in oxidation possible interactions AO substrates inhibitors has not been investigated more details. present study, XO 6- mercaptopurine investigated. 6-Mercaptopurine was incubated with bovine milk partially purified guinea pig liver hydroxylase fractions absence presence inhibitor/substrates, reactions were monitored spectrophotometric HPLC methods. According results obtained from inhibition sudies, it likely via rather than 8-oxo-6-mercaptopurine. The first step which rate limiting catalized solely XO, whereas both are involved acid.
sci-hub.se 参考文章(35)
C. Auscher, C. Pasquier, N. Mercier, F. Delbarre, Urinary Excretion of 6 Hydroxylated Metabolite and Oxypurines in a Xanthinuric Man Given Allopurinol or Thiopurinol Advances in Experimental Medicine and Biology. ,vol. 41, pp. 663- 667 ,(1974) , 10.1007/978-1-4757-1433-3_37
K.V. Rajagopalan, Irwin Fridovich, Philip Handler, Hepatic aldehyde oxidase. I. Purification and properties. Journal of Biological Chemistry. ,vol. 237, pp. 922- 928 ,(1964) , 10.1016/S0021-9258(18)60394-1
Philip J. Sherratt, John D. Hayes, Glutathione S-transferases Enzyme Systems that Metabolise Drugs and Other Xenobiotics. pp. 319- 352 ,(2002) , 10.1002/0470846305.CH9
Thomas Spector, Willard W. Hall, Thomas A. Krenitsky, Human and bovine xanthine oxidases. Inhibition studies with oxipurinol. Biochemical Pharmacology. ,vol. 35, pp. 3109- 3114 ,(1986) , 10.1016/0006-2952(86)90394-1
R J Chenery, A W Harrell, S E Clarke, Role of aldehyde oxidase in the in vitro conversion of famciclovir to penciclovir in human liver. Drug Metabolism and Disposition. ,vol. 23, pp. 251- 254 ,(1995)
C W Keuzenkamp-Jansen, J M van Baal, R A De Abreu, J G de Jong, R Zuiderent, J M Trijbels, Detection and identification of 6-methylmercapto-8-hydoxypurine, a major metabolite of 6-mercaptopurine, in plasma during intravenous administration. Clinical Chemistry. ,vol. 42, pp. 380- 386 ,(1996) , 10.1093/CLINCHEM/42.3.380
Christine Johnson, Christine Stubley-Beedham, J. Godfrey, P. Stell, Hydralazine: A potent inhibitor of aldehyde oxidase activity in vitro and in vivo Biochemical Pharmacology. ,vol. 34, pp. 4251- 4256 ,(1985) , 10.1016/0006-2952(85)90280-1
Thomas A. Krenitsky, Shannon M. Neil, Gertrude B. Elion, George H. Hitchings, A comparison of the specificities of xanthine oxidase and aldehyde oxidase Archives of Biochemistry and Biophysics. ,vol. 150, pp. 585- 599 ,(1972) , 10.1016/0003-9861(72)90078-1
Yuji Moriwaki, Tetsuya Yamamoto, Yumiko Nasako, Sumio Takahashi, Michio Suda, Keisai Hiroishi, Toshikazu Hada, Kazuya Higashino, In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochemical Pharmacology. ,vol. 46, pp. 975- 981 ,(1993) , 10.1016/0006-2952(93)90661-F
Solomon Zimm, John J. Grygiel, John M. Strong, Terrence J. Monks, David G. Poplack, Identification of 6-mercaptopurine riboside in patients receiving 6-mercaptopurine as a prolonged intravenous infusion Biochemical Pharmacology. ,vol. 33, pp. 4089- 4092 ,(1984) , 10.1016/0006-2952(84)90026-1