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Chemical Compound Review

ITP     [[[(2R,3S,4R,5R)-3,4- dihydroxy-5-(6-oxo-3H...

Synonyms: Inosine 5, CHEMBL1233686, CHEBI:16039, HMDB00189, bmse000255, ...
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Disease relevance of inosine triphosphate


Psychiatry related information on inosine triphosphate

  • The results concerning the association of HLA antigens with ITP, pernicious anaemia, hemangiomas and Alzheimer's disease are compared with those of other authors and the causes for differences are discussed [6].

High impact information on inosine triphosphate

  • Brush border contraction occurs with ATP or with a mixture of ITP and ATP gamma S. Therefore, phosphorylation regulates myosin association with the cytoskeleton, myosin is not bound at the actin-myosin binding site, and when phosphorylated, myosin forms filaments for movement [7].
  • Sera from 48% of patients with chronic ITP and 2 of 8 patients with acute ITP contain antibodies that bind to the 50-kD fragment in an ELISA [2].
  • Sequelae of treatment of ITP with anti-D (Rho) immunoglobulin [8].
  • Using ITP (a substrate for myosin II ATPase) and/or ATP gamma S (a substrate for myosin II heavy-chain kinase [MHCK]), we demonstrated that phosphorylation of myosin heavy chains occurred at the foci within the actin network, a result that suggests that MHCK was localized at the foci [9].
  • Because ITP will not serve as a substrate for MLCK, this finding suggests that Mg2+-activation of contraction does not require myosin phosphorylation [10].

Chemical compound and disease context of inosine triphosphate

  • PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity [11].
  • Peak I and Peak II RNA endowed receptor activity in the oocyte that was pharmacologically indistinguishable: ADP and AMP were inactive whereas UTP and ITP exhibited activity that was similar in potency to that of ATP gamma S. Both Peak I and Peak II ATP gamma S-dependent activity was inhibited by pertussis toxin [12].
  • Vaccinia ligase catalyzed efficient strand joining on nicked DNAs in the presence of magnesium and ATP (Km = 95 microM). dATP, ITP, AMPPCP, 3'dATP, and ATP alpha S could not substitute for ATP; of these, 3'dATP and ATP alpha S were inhibitors of ligation [13].
  • Moreover, small doses of the initial prednisolone therapy for ITP might also be recommended to avoid thrombus formations in the atherosclerotic lesions [14].
  • CONCLUSIONS: ITP can be associated with metastatic pancreatic adenocarcinoma and can respond well to steroid treatment [15].

Biological context of inosine triphosphate

  • Although ITP and GTP serve as myosin ATPase substrates, they do not cause BB contraction, myosin release, or phosphorylation [7].
  • Substituting ITP for GTP or using an S100 cell-free extract as a source of antiterminator permitted transcription of the bioBFCD gene cluster initiating at the promoter pB to be read through [16].
  • Upon addition and hydrolysis of ITP or ATP, a rapid phosphate-oxygen exchange is observed even with 0.15 mM Ca2+ present and a definite but smaller exchange at 8 mM Ca2+ [17].
  • At pH 6.0-7.0, an apparent negative cooperativity is observed when mutant F1 hydrolyzes GTP or ITP, whereas the wild-type enzyme shows Michaelian kinetics [18].
  • ITP is a competitive inhibitor against both IDP and P-enolpyruvate, suggesting overlapping binding sites for the two substrates on the enzyme [19].

Anatomical context of inosine triphosphate

  • Analysis by video enhanced differential interference-contrast microscopy and thin-section transmission electron microscopy reveals contractions in the terminal web region causing microvilli to be fanned apart in response to ATP and delta S-ATP but not in response to ADP, PPi, ITP, or GTP [20].
  • Whole epithelial sheets were glycerinated, which leaves the brush border and intercellular junctions intact, and then treated with ATP, PPi, ITP, ADP, GTP, or delta S-ATP [20].
  • Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP [21].
  • Platelets from 24 patients with immune thrombocytopenia resistant to standard therapy (refractory ITP), 35 patients with nonimmune thrombocytopenia (non-ITP), and 32 normal donors were studied in regard to platelet surface-bound IgG (PBIgG) and the ability of these platelets to be bound by human monocytes in vitro (monocyte-platelet rosette assay) [22].
  • Substrate regulation of calcium binding in Ca2+-ATPase molecules of the sarcoplasmic reticulum. II. Effect of CTP, GTP, ITP, and UTP [23].

Associations of inosine triphosphate with other chemical compounds

  • IDP inhibited ITP hydrolysis and caused positive cooperativity [24].
  • The hydrolyzable nucleotides GTP, ITP, and ATP are excellent promoters of the hydrolysis of previously bound TNP-[gamma-32P]ATP whereas addition of nonhydrolyzable nucleotides such as TNP-ADP, ADP, and adenylyl imidodiphosphate result in a lower rate and extent of hydrolysis [25].
  • In the present work, we found slow 5-oxoproline-dependent changes in the rates of hydrolysis of ITP, GTP, and UTP [26].
  • Without added Mg2+, Ca2+ stimulated the hydrolysis of several other nucleotides: ATP congruent to GTP congruent to CTP congruent to ITP greater than UTP, but Ca2+-stimulated ATPase was not coupled to uptake of Ca2+, even in the presence of 5 mM oxalate [27].
  • Phosphorylation of the ATPase was observed for ITP and 2'-deoxy-ATP, but not for 3'-deoxy-ATP [28].

Gene context of inosine triphosphate

  • Intracellular concentrations of the nucleotide inosine triphosphate (ITP) are regulated by ITP-ase (EC, which is encoded by ITPA on chromosome 20p [29].
  • We found increases in MCP-1 and RANTES levels in ITP patients compared with those in healthy individuals [30].
  • The pathogenesis of ITP may in some patients include alterations of the CD40/CD40L pathway [30].
  • The following loci could not be localized with full confidence: LDHA, NP, PEPD, ITP, and PGK [31].
  • The EF-3 effect is manifest in the presence of ATP, GTP, or ITP [32].

Analytical, diagnostic and therapeutic context of inosine triphosphate

  • Combination chemotherapy for ITP [33].
  • Seventeen of 24 (71%) of the ITP patients had platelets which demonstrated increased monocyte-platelet rosette formation [rosette index (RI) greater than 2], whereas only four (11%) of the non-ITP patients had such platelets [22].
  • Reverse-phase high-performance liquid chromatography analysis additionally shows that this enzyme has broad substrate specificity toward other nucleotides, UTP, UDP, ITP, and IDP [34].
  • In general, these techniques belong either to the family of displacement methods, e.g., ITP, or to the gradient methods, e.g., gradient-elution HPLC [35].
  • Under experimental conditions in which the self-association of the purine-nucleoside 5'-triphosphates (PuNTPs) GTP and ITP is negligible, potentiometric pH titrations were carried out to determine the stabilities of the M(H;PuNTP) and M(PuNTP)2-complexes where M2+ = Mg2+, Ca2+, Sr2+ [36].


  1. Chronic immune thrombocytopenic purpura in monozygotic twins: genetic factors predisposing to ITP. Laster, A.J., Conley, C.L., Kickler, T.S., Dorsch, C.A., Bias, W.B. N. Engl. J. Med. (1982) [Pubmed]
  2. Localization of human platelet autoantigens to the cysteine-rich region of glycoprotein IIIa. Kekomaki, R., Dawson, B., McFarland, J., Kunicki, T.J. J. Clin. Invest. (1991) [Pubmed]
  3. Helicobacter pylori and chronic ITP: the discrepancy in the clinical responses to eradication therapy might be due to differences in the bacterial strains. Takahashi, T., Yujiri, T., Tanizawa, Y. Blood (2004) [Pubmed]
  4. Severe hemolysis following administration of Rh(o)(D) immune globulin in an ITP patient associated with anti-C. Schwartz, J., Spitalnik, S., Grima, K.M. Blood (2006) [Pubmed]
  5. Phase I evaluation of sequential doxorubicin gemcitabine then ifosfamide paclitaxel cisplatin for patients with unresectable or metastatic transitional-cell carcinoma of the urothelial tract. Dodd, P.M., McCaffrey, J.A., Hilton, S., Mazumdar, M., Herr, H., Kelly, W.K., Icasiano, E., Boyle, M.G., Bajorin, D.F. J. Clin. Oncol. (2000) [Pubmed]
  6. Some critical remarks on the problem of HLA association with disease. Májský, A., Korínková, P., Fortýnová, J., Abrahámová, J., Vojtĕchovský, M. Folia Haematol. Int. Mag. Klin. Morphol. Blutforsch. (1981) [Pubmed]
  7. Phosphorylation controls brush border motility by regulating myosin structure and association with the cytoskeleton. Broschat, K.O., Stidwill, R.P., Burgess, D.R. Cell (1983) [Pubmed]
  8. Sequelae of treatment of ITP with anti-D (Rho) immunoglobulin. Imbach, P., Kühne, T. Lancet (2000) [Pubmed]
  9. Release of myosin II from the membrane-cytoskeleton of Dictyostelium discoideum mediated by heavy-chain phosphorylation at the foci within the cortical actin network. Yumura, S., Kitanishi-Yumura, T. J. Cell Biol. (1992) [Pubmed]
  10. Calcium-independent contraction in lysed cell models of teleost retinal cones: activation by unregulated myosin light chain kinase or high magnesium and loss of cAMP inhibition. Burnside, B., Ackland, N. J. Cell Biol. (1987) [Pubmed]
  11. Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial. Bajorin, D.F., McCaffrey, J.A., Hilton, S., Mazumdar, M., Kelly, W.K., Scher, H.I., Spicer, J., Herr, H., Higgins, G. J. Clin. Oncol. (1998) [Pubmed]
  12. Characterization of phagocyte P2 nucleotide receptors expressed in Xenopus oocytes. Murphy, P.M., Tiffany, H.L. J. Biol. Chem. (1990) [Pubmed]
  13. Vaccinia virus DNA ligase: specificity, fidelity, and inhibition. Shuman, S. Biochemistry (1995) [Pubmed]
  14. A rare case of arteriosclerosis obliterans without prominent risk factors complicated by idiopathic thrombocytopenic purpura. A case report. Yamagishi, S., Ohta, M., Segawa, C., Abe, T., Sawada, T. Angiology. (1996) [Pubmed]
  15. Idiopathic thrombocytopenic purpura in a newly diagnosed pancreatic adenocarcinoma. Bir, A., Bshara, W., George, M., Fakih, M.G. JOP (2006) [Pubmed]
  16. Abortive termination of bioBFCD RNA synthesized in vitro from the bioABFCD operon of Escherichia coli K-12. Nath, S.K., Guha, A. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  17. Induction by nucleotide triphosphate hydrolysis of a form of sarcoplasmic reticulum ATPase capable of medium phosphate-oxygen exchange in presence of calcium. de Meis, L., Boyer, P.D. J. Biol. Chem. (1978) [Pubmed]
  18. Glutamine 170 to tyrosine substitution in yeast mitochondrial F1 beta-subunit increases catalytic site interaction with GDP and IDP and produces negative cooperativity of GTP and ITP hydrolysis. Jault, J.M., Divita, G., Allison, W.S., Di Pietro, A. J. Biol. Chem. (1993) [Pubmed]
  19. Purification and characterization of phosphoenolpyruvate carboxykinase from the parasitic helminth Ascaris suum. Rohrer, S.P., Saz, H.J., Nowak, T. J. Biol. Chem. (1986) [Pubmed]
  20. Reactivation of intestinal epithelial cell brush border motility: ATP-dependent contraction via a terminal web contractile ring. Burgess, D.R. J. Cell Biol. (1982) [Pubmed]
  21. Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP. Stahl, C.P., Zucker-Franklin, D., McDonald, T.P. Blood (1986) [Pubmed]
  22. Monocyte-platelet interaction in immune and nonimmune thrombocytopenia. Saleh, M.N., Moore, D.L., Lee, J.Y., LoBuglio, A.F. Blood (1989) [Pubmed]
  23. Substrate regulation of calcium binding in Ca2+-ATPase molecules of the sarcoplasmic reticulum. II. Effect of CTP, GTP, ITP, and UTP. Nakamura, J., Tajima, G., Sato, C. J. Biol. Chem. (2002) [Pubmed]
  24. Effect of inosine 5' -(beta, gamma-imido) triphosphate and other nucleotides on beef heart mitochondrial ATPase. Schuster, S.M., Gertschen, R.J., Lardy, H.A. J. Biol. Chem. (1976) [Pubmed]
  25. Cooperatively between catalytic sites in the mechanism of action of beef heart mitochondrial adenosine triphosphatase. Grubmeyer, C., Penefsky, H.S. J. Biol. Chem. (1981) [Pubmed]
  26. Interaction of 5-oxo-L-prolinase with nucleoside triphosphates. Evidence suggesting substrate-dependent conformational change. Griffith, O.W., Meister, A. J. Biol. Chem. (1982) [Pubmed]
  27. Ca2+-stimulated, Mg2+-dependent ATPase activity in neutrophil plasma membrane vesicles. Coupling to Ca2+ transport. Ochs, D.L., Reed, P.W. J. Biol. Chem. (1984) [Pubmed]
  28. Mapping interactions between the Ca2+-ATPase and its substrate ATP with infrared spectroscopy. Liu, M., Barth, A. J. Biol. Chem. (2003) [Pubmed]
  29. DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency. Cao, H., Hegele, R.A. J. Hum. Genet. (2002) [Pubmed]
  30. Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura. Nagahama, M., Nomura, S., Kanazawa, S., Ozaki, Y., Kagawa, H., Fukuhara, S. Eur. J. Haematol. (2002) [Pubmed]
  31. Comparative gene mapping of man and Cebus capucinus: a study of 23 enzymatic markers. Créau-Goldberg, N., Cochet, C., Turleau, C., de Grouchy, J. Cytogenet. Cell Genet. (1981) [Pubmed]
  32. Role of yeast elongation factor 3 in the elongation cycle. Kamath, A., Chakraburtty, K. J. Biol. Chem. (1989) [Pubmed]
  33. Combination chemotherapy for ITP. Kao, N.L., Richmond, G.W. N. Engl. J. Med. (1993) [Pubmed]
  34. ATP-consuming and ATP-generating Enzymes Secreted by Pancreas. Yegutkin, G.G., Samburski, S.S., Jalkanen, S., Novak, I. J. Biol. Chem. (2006) [Pubmed]
  35. Several new electrofocusing techniques. Ivory, C.F. Electrophoresis (2007) [Pubmed]
  36. Stabilities and isomeric equilibria in solutions of monomeric metal-ion complexes of guanosine 5'-triphosphate (GTP4-) and inosine 5'-triphosphate (ITP4-) in comparison with those of adenosine 5'-triphosphate (ATP4-). Sigel, H., Bianchi, E.M., Corfù, N.A., Kinjo, Y., Tribolet, R., Martin, R.B. Chemistry (Weinheim an der Bergstrasse, Germany) (2001) [Pubmed]
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