Inosine triphosphate pyrophosphatase

Fig. 13.1 Pathways of thiopurine metabolism. The positions of two polymorphically expressed enzymes, TPMT (thiopurine methyl transferase) and ITPA (inosine triphosphate pyrophosphatase), are shown. HGPRT, hypoxanthine guanine phosphoribosyl transferase 6-TIDP, 6-thioi-nosine diphosphate 6-TIMP, 6-thioinosine monophosphate 6-TITP, 6-thio inosine trinophosphate...

Inosine triphosphate pyrophosphatase (TTPA) deficiency may lead to accumulation of 6-thioinosine triphosphate (ITP) in those treated with AZA or 6-MP. The gene encoding ITPA is located on chromosome 20, and two of five single-nucleotide... 

Marinaki, A. M., Ansari, A., Duley, J. A., et al. (2004) Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics. 14,181-187. 

Zelinkova, Z., Deiijks, L. J., Stokkers, P. C., et al. (2006) Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin. Gastroenterol. Hepatol. 4, 44-49. 

Shipkova M, Franz J, Abe M, Klett C, Wieland E, Andus T (2011) Association between adverse effects under azathioprine therapy and inosine triphosphate pyrophosphatase activity in patients with chronic inflammatory bowel disease. Ther Drug Monit 33 321-328... 

Stocco G, Cheok MH, Crews KRet al (2009) Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther 85 164-172... 

This enzyme activity has been observed in myosin and actomyosin, mitochondria, microsomes, and cell membranes. In some cases magnesium ions function as an activator, in others calcium ions, and in still others, both calcium and magnesium are requited. Another form of adenosine-triphosphatase is stimulated by sodium and potassium ions and is inhibited by ouabain. Some forms of the enzyme can hydrolyse inosine triphosphate and other nucleoside-5 -triphosphates. The substrate specificity may depend upon the activating divalent cation and on the presence of monovalent cations. These enzymes are probably important components of a system responsible for facilitating cation transfer in membranes. They should not be confused with adenosine triphosphate pyrophosphatase E.C. 3.6.1.8. 

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