+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Nature and position of functional group on thiopurine substrates influence activity of xanthine oxidase - Enzymatic reaction pathways of 6-mercaptopurine and 2-mercaptopurine are different



Nature and position of functional group on thiopurine substrates influence activity of xanthine oxidase - Enzymatic reaction pathways of 6-mercaptopurine and 2-mercaptopurine are different



Biochemistry 72(2): 170-177



Xanthine oxidase-catalyzed hydroxylation reactions of the anticancer drug 6-mercaptopurine (6-MP) and its analog 2-mercaptopurine (2-MP) as well as 6-thioxanthine (6-TX) and 2-thioxanthine (2-TX) have been studied using UV-spectroscopy, high pressure liquid chromatography, photodiode array, and liquid chromatography-based mass spectral analysis. It is shown that 6-MP and 2-MP are oxidatively hydroxylated through different pathways. Enzymatic hydroxylation of 6-MP forms 6-thiouric acid in two steps involving 6-TX as the intermediate, whereas 2-MP is converted to 8-hydroxy-2-mercaptopurine as the expected end product in one step. Surprisingly, in contrast to the other thiopurines, enzymatic hydroxylation of 2-MP showed a unique hyperchromic effect at 264 nm as the reaction proceeded. However, when 2-TX is used as the substrate, it is hydroxylated to 2-thiouric acid. The enzymatic hydroxylation of 2-MP is considerably faster than that of 6-MP, while 6-TX and 2-TX show similar rates under identical reaction conditions. The reason why 2-MP is a better substrate than 6-MP and how the chemical nature and position of the functional groups present on the thiopurine substrates influence xanthine oxidase activity are discussed.

(PDF emailed within 0-6 h: $19.90)

Accession: 012996128

Download citation: RISBibTeXText

PMID: 17367294

DOI: 10.1134/s000629790702006x


Related references

Adsorption of 6-mercaptopurine and 6-mercaptopurine-ribosideon silver colloid: a pH-dependent surface-enhanced Raman spectroscopy and density functional theory study. II. 6-mercaptopurine-riboside. Biopolymers 78(6): 298-310, 2005

6-Mercaptopurine-related leucopenia and in vivo xanthine oxidase activity. Lancet 2(8511): 869-870, 1986

In vitro oxidative metabolism of 6-mercaptopurine in human liver: insights into the role of the molybdoflavoenzymes aldehyde oxidase, xanthine oxidase, and xanthine dehydrogenase. Drug Metabolism and Disposition: the Biological Fate of Chemicals 42(8): 1334-1340, 2015

Depression of primary immunity reaction due to 6-mercaptopurine and cyclophosphamide in various animal species: II. Various influence on antibody formation in rabbits, guinea pigs, rats, and mice due to 6-mercaptopurine and cyclophos-phamide. Z Gesamte Exp Med Exp Chir 143(2): 105-120, 1967

In vitro study of 6-mercaptopurine oxidation catalysed by aldehyde oxidase and xanthine oxidase. Drug Metabolism and Pharmacokinetics 22(4): 299-306, 2007

A comparison of the effectiveness of standard dose 6-mercaptopurine, combination 6-mercaptopurine and DON, and high-loading 6-mercaptopurine therapies in the treatment of acute leukemia in children Results of a cooperative study. Cancer Chemother Repts: 1-164, 1962

A comparison of the effectiveness of standard dose 6-mercaptopurine, combination 6-mercaptopurine and DON, and high-loading 6-mercaptopurine therapies in treatment of the acute leukemias of childhood: results of a coperative study. Cancer ChemoTherapy Reports 18: 83-95, 1962

6-Mercaptopurine-induced histopathological changes and xanthine oxidase expression in rat placenta. Journal of Toxicological Sciences 37(3): 607-615, 2012

Potentiation of the inhibition of xanthine oxidase by a combination of 6-mercaptopurine and 6-thioguanine. Experientia 37(2): 175-176, 1981

Studies on the mechanism of action of 6-mercaptopurine. Interaction with copper and xanthine oxidase. Biochemical Journal 193(3): 799-803, 1981

The use of xanthine oxidase ec 1.2.3.2 for a specific and sensitive fluorometric determination of 6 mercaptopurine in serum. Biochemical Medicine 32(3): 303-310, 1984

The use of xanthine oxidase for a specific and sensitive fluorimetric determination of 6-mercaptopurine in serum. Biochemical Medicine 32(3): 303-310, 1984