Isolation and identification of inosine triphosphate from human erythrocytes

Zachara, B; Lewandowski, Jan

doi:10.1016/0005-2787(74)90190-7

Cited by 18 publications

(11 citation statements)

References 23 publications

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“…A diffuse but clearly non-nuclear distribution of fluorescence was observed. 2 Enzymological analysis of the recombinant human protein expressed from this cDNA clone showed a high specificity for the hydrolysis of ITP, dITP, and XTP to their respective monophosphates. Characteristics of the recombinant enzyme were similar to those from earlier reports of ITPase isolated from human tissues, except the K m value for ITP, which at 0.51 mM was higher than those previously reported, 0.13 (12) and 0.07 mM (6).…”

Section: Discussionmentioning

confidence: 90%

“…It is generated by pyrophosphorylation or stepwise phosphorylation of IMP, an essential metabolite of purine biosynthesis and a precursor of both AMP and GMP (1)(2)(3). The deoxyribonucleotide dITP may be generated from dATP by slow, non-enzymatic hydrolysis or by reduction of ITP (3).…”

mentioning

confidence: 99%

“…Normally, the cellular ITP/dITP concentration is very low. The inability to demonstrate the synthesis of ITP/dITP in cellular preparations has been attributed to the presence in the cytoplasm of an inosine triphosphatase (ITPase), 1 an enzyme that does not permit accumulation of these nucleotides (2).…”

mentioning

confidence: 99%

“…XTP is also a substrate, but activity toward other purine nucleoside triphosphates is low, whereas no activity is found with IDP or IMP (2)(3)(4)(5)(6). Different studies have measured different K m values for ITP (2, 6 -12), but in all cases an alkaline pH optimum and an absolute requirement for a divalent ion such as Mg 2ϩ or Mn 2ϩ has been found.…”

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confidence: 99%

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Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

Lin

McLennan

Kong

et al. 2001

Journal of Biological Chemistry

129

156

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ITP and dITP exist in all cells. dITP is potentially mutagenic, and the levels of these nucleotides are controlled by inosine triphosphate pyrophosphatase (EC 3.6.1.19). Here we report the cloning, expression, and characterization of a 21.5-kDa human inosine triphosphate pyrophosphatase (hITPase), an enzyme whose activity has been reported in many animal tissues and studied in populations but whose protein sequence has not been determined before. At the optimal pH of 10.0, recombinant hITPase hydrolyzed ITP, dITP, and xanthosine 5-triphosphate to their respective monophosphates whereas activity with other nucleoside triphosphates was low. K m values for ITP, dITP, and xanthosine 5-triphosphate were 0.51, 0.31, and 0.57 mM, respectively, and k cat values were 580, 360, and 640 s ؊1 , respectively. A divalent cation was absolutely required for activity. The gene encoding the hITPase cDNA sequence was localized by radiation hybrid mapping to chromosome 20p in the interval D20S113-D20S97, the same interval in which the ITPA inosine triphosphatase gene was previously localized. A BLAST search revealed the existence of many similar sequences in organisms ranging from bacteria to mammals. The function of this ubiquitous protein family is proposed to be the elimination of minor potentially mutagenic or clastogenic purine nucleoside triphosphates from the cell.

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Section: Discussionmentioning

confidence: 90%

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confidence: 99%

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Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

Lin

McLennan

Kong

et al. 2001

Journal of Biological Chemistry

129

156

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“…Myelosuppression during aza therapy seems not to be related to ITPA gene mutations (18 ). ITPA catalyzes the hydrolysis of inosine triphosphate to inosine monophosphate (and the 6-thio derivatives thereof), thereby recycling (6-thio)purines that might otherwise be trapped in the form of (6-thio)inosine triphosphate (15,46 ). The ITPA 94CϾA mutation codes for a Pro32Thr exchange.…”

Section: Discussionmentioning

confidence: 99%

Association of Inosine Triphosphatase 94C>A and Thiopurine S-Methyltransferase Deficiency with Adverse Events and Study Drop-Outs under Azathioprine Therapy in a Prospective Crohn Disease Study

et al. 2005

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Background: Azathioprine (aza) therapy is beneficial in the treatment of inflammatory bowel disease, but 10%-30% of patients cannot tolerate aza therapy because of adverse drug reactions. Thiopurine S-methyltransferase (TPMT) deficiency predisposes to myelotoxicity, but its association with other side effects is less clear. Inosine triphosphatase (ITPA) mutations are other pharmacogenetic polymorphisms possibly involved in thiopurine metabolism and tolerance. Methods: We analyzed data from a 6-month prospective study including 71 patients with Crohn disease undergoing first-time aza treatment with respect to aza intolerance. Patients were genotyped for common TPMT and ITPA mutations and had pretherapy TPMT activity measured.

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ITP pyrophosphohydrolase and idp phosphohydrolase in rat tissue

Vanderheiden

1975

Journal Cellular Physiology

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The existence of a nucleoside triphosphate pyrophosphohydrolase specific for ITP has been demonstrated in the cytosol fraction of a variety of rat tissues. The enzyme, stable to moderate heat treatment, was present in erythrocytes as well as brain, heart, kidney, liver, lung, muscle, ovaries, spleen, testes and thymus. The specific activity of the enzyme ranges from 26 to 150 mumoles/min/g protein. In addition, evidence is given for a heat labile nucleoside diphosphate (IDP) phosphohydrolase present in most rat tissues, and particularly high in the adrenal (137 mumoles/min/g protein). An "ITP-IMP cycle" is proposed as a rgulating mechanism for intracellular levels of ATP.

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Isolation and identification of inosine triphosphate from human erythrocytes

Cited by 18 publications

References 23 publications

Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

Association of Inosine Triphosphatase 94C>A and Thiopurine S-Methyltransferase Deficiency with Adverse Events and Study Drop-Outs under Azathioprine Therapy in a Prospective Crohn Disease Study

ITP pyrophosphohydrolase and idp phosphohydrolase in rat tissue

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Isolation and identification of inosine triphosphate from human erythrocytes

Cited by 18 publications

References 23 publications

Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

Association of Inosine Triphosphatase 94C&gt;A and Thiopurine S-Methyltransferase Deficiency with Adverse Events and Study Drop-Outs under Azathioprine Therapy in a Prospective Crohn Disease Study

ITP pyrophosphohydrolase and idp phosphohydrolase in rat tissue

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Association of Inosine Triphosphatase 94C>A and Thiopurine S-Methyltransferase Deficiency with Adverse Events and Study Drop-Outs under Azathioprine Therapy in a Prospective Crohn Disease Study