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At least 19 recordsLinked to original sources
PubMed1990

Effect of dipyridamole on inosine triphosphate pyrophosphohydrolase activity and inosine triphosphate content in fresh human erythrocytes incubated with adenosine.

The activity of inosine triphosphate pyrophosphohydrolase (ITPH) in human erythrocytes was found to be 1.50 +/- 0.39 mumol of inosine triphosphate (ITP) hydrolysed x min-1 per g Hb, and no measurable amount of ITP was detected. When dipyridamole was added to the medium composed of adenosine, pyruvate and inorganic phosphate, ITPH activity was 1.18 +/- 0.41, and at the same time ITP accumulation was 0.61 +/- 0.31 mumol/g Hb. The negative correlation between ITPH activity and accumulation of ITP was r = -0.87 at P less than 0.001.

Adenosine↗
PubMed1997

Functionally nonequivalent interactions of guanosine 5'-triphosphate, inosine 5'-triphosphate, and xanthosine 5'-triphosphate with the retinal G-protein, transducin, and with Gi-proteins in HL-60 leukemia cell membranes.

G-proteins mediate signal transfer from receptors to effector systems. In their guanosine 5'-triphosphate (GTP)-bound form, G-protein alpha-subunits activate effector systems. Termination of G-protein activation is achieved by the high-affinity GTPase [E.C. 3.6.1.-] of their alpha-subunits. Like GTP, inosine 5'-triphosphate (ITP) and xanthosine 5'-triphosphate (XTP) can support effector system activation. We studied the interactions of GTP, ITP, and XTP with the retinal G-protein, transducin (TD), and with G-proteins in HL-60 leukemia cell membranes. TD hydrolyzed nucleoside 5'-triphosphates (NTPs) in the order of efficacy GTP > ITP > XTP. NTPs eluted TD from rod outer segment disk membranes in the same order of efficacy. ITP and XTP competitively inhibited TD-catalyzed GTP hydrolysis. In HL-60 membranes, the chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and leukotriene B4 (LTB4) effectively activated GTP and ITP hydrolysis by Gi-proteins. fMLP and LTB4 were at least 10-fold more potent activators of ITPase than of GTPase. Complement C5a effectively activated the GTPase of Gi-proteins but was only a weak stimulator of ITPase. The potency of C5a to activate GTP and ITP hydrolysis was similar. The fMLP-stimulated GTPase had a lower Km value than the fMLP-stimulated ITPase, whereas the opposite was true for the Vmax values. fMLP, C5a, and LTB4 did not stimulate XTP hydrolysis. Collectively, our data show that GTP, ITP, and XTP bind to G-proteins with different affinities, that G-proteins hydrolyze NTPs with different efficacies, and that chemoattractants stimulate GTP and ITP hydrolysis by Gi-proteins in a receptor-specific manner. On the basis of our results and the data in the literature, we put forward the hypothesis that GTP, ITP, and XTP act as differential signal amplifiers and signal sorters at the G-protein level.

Animals↗
PubMed1977

Temperature dependence of the decay of the UV absorption difference spectrum of heavy meromyosin induced by adenosine triphosphate and inosine triphosphate.

The UV absorption difference spectrum of heavy meromyosin induced by ATP was measured at various temperatures. At higher temperatures, the difference spectrum formed rapidly after adding ATP and continued steadily during the steady state which we have called the ATP-form of difference spectrum. At lower temperatures, the ATP-form of difference spectrum decayed into the other form before the steady state was attained. This was identical to the difference spectrum obtained by adding ADP and has been called the ADP-form of difference spectrum. At intermediate temperatures, biphasic decay was observed. The results indicate that the dominant intermediate at the steady state is altered from the one showing the ATP-form of difference spectrum at higher temperatures to that showing the ADP-form at lower temperatures. The population of the two intermediates depends on the temperature between the two extremes. This temperature-induced transition was observed in the presence of any divalent cation such as Mg2+, Mn2+, or Ca2+. A similar transition was observed with the difference spectrum induced by ITP in the presence of MgCl2. The pH dependence of the single early decay of the ATP-induced difference spectrum was measured in the presence of MnCl2 at 1 degree. The apparent rate constant of the decay showed a biphasic pH dependence, having the same shape as the pH activity curve of ATPase [EC 3.6.1.3] observed at higher temperatures. The rate determining step for the steady state ATPase at higher temperatures is thought to be the step of changing from the intermediate complex showing the ATP-form of difference spectrum to that showing the ADP-form. This is inconsistent with our previous mechanism (Yazawa, M. et al. (1973) J. Biochem. 74, 1107-1117). The rate determining step at lower temperatures was assigned as a step of ADP dissociation.

Adenosine Diphosphate↗
PubMed1979

Purification and properties of human erythrocyte inosine triphosphate pyrophosphohydrolase.

Inosine triphosphate pyrophosphohydrolase from human erythrocytes was purified and characterized. The enzyme is highly specific for ITP and shows optimal activity in glycine buffer pH 9.6 and 50 mM MgCl2. The Km of the enzyme is 1.3 X 10(-4), the Vmax = 1.2 X 10(-9) and the Keq = 3.8 X 10(4). Human erythrocyte ITP pyrophosphohydrolase does not require SH compounds for activation. The enzyme is inhibited by Cd++, Co++, and Ca++ ions and by p-hydroxymercuribenzoate.

Cations, Divalent↗
PubMed1979

Nonparallel isometric tension response of rabbit soleus skinned muscle fibers to magnesium adenosine triphosphate and magnesium inosine triphosphate.

The isometric tension response of single "skinned' rabbit soleus muscle fibers to MgATP and McITP in the absence of calcium was studied. [MgATP] or [MgITP] was varied in solutions of ionic strength 0.30 and temperature 20 degrees C. Steady-state tension that developed in MgATP or MgITP solutions was a biphasic bell-shaped function of log [MgATP] or log [MgITP] which increased from zero to maximum tension and then declined again to zero. Analysis of the data showed that, under comparable ionic conditions, percent tension vs. log [MgATP] and percent tension vs. log [MgITP] curves are not parallel. Instead, the percent tension vs. log [MgITP] curve is much broader. Additionally, under comparable ionic conditions maximum tension in MgITP solutions was higher than in MgATP solutions. In addition, in MgATP solutions, pH, [K+], and excess ATP were varied. Raising pH from 7 to 8, [K+] from 46 mM to 200 mM, or decreasing excess ATP from 2 to 0.5 mM all increased maximum tension. None of these factors, however, influenced the shape or position of the percent tension vs. log [MgATP] curve.

Adenosine Triphosphate↗
PubMed1976

Relationships between nucleoside triphosphate pyrophosphohydrolase activity and inosine triphosphate accumulation in human erythrocytes.

The relationship between nucleoside triphosphate pyrophosphohydrolast (NTPH) (EC 3.6.1.19) activity in erythrocyte lysates and accumulation of radioactive inosine triphosphate (ITP) in human erythrocytes incubated in vitro with [14C]hypoxanthine, was studied in 93 humans. When ITP accumulation, expressed as percentage of total radioactive nucleotides, was plotted against NTPH specific activity, an inverse relationship was found to exist. A continous spectrum of NTPH specific activities and ITP accumulation values exists in the human population and the relationship between these two parameters follows the relationship of substrate concentration to enzyme activity predicted by Michaelis-Menten enzyme kinetics. One interpretation of these data is that the ITP concentration in human red blood cells is controlled by the degradation of ITP to IMP and pyrophosphate catalyzed by NTPH.

Erythrocytes↗
PubMed1998

Identification of stable RNA hairpins causing band compression in transcriptional sequencing and their elimination by use of inosine triphosphate.

To identify stable RNA secondary structure causing band compression, 30 lambda DNA clones and four cDNA clones (about 10 kb in total length) were sequenced using Transcriptional Sequencing, which is based on the phage RNA polymerase chain termination reaction with fluorescent 3' deoxynucleoside triphosphate, using the canonical set of rNTPs for the substrate. Electrophoresis was performed on acrylamide gel containing 7 M urea at 50 degrees C using ABI 377 DNA sequencer. A total of 159 band compressions were identified, and most compression sites seem to be due to hairpin structures. We also found that the presence of rITP in place of rGTP in the sequencing reaction can entirely eliminate all band compressions. The use of rITP gave a better peak uniformity and resolution in the sequencing gel in the case of lambda DNA than with c7rGTP, leading to improved accuracy in the sequence determination. Substitution of the base analog rITP for rGTP should be useful for accurate sequencing determination.

Bacteriophage lambda↗
PubMed1975

Individual variation in inosine triphosphate accumulation in human erythrocytes.

Erythrocytes from 5% of a normal population accumulated relatively high amounts of radioactive inosine triphosphate (i.e., greater than 70 nmoles/10(10) cells in 2 hr) when they were incubated with [14C]hypoxanthine. The incidence of this characteristic in a mentally retarded population was 16%. Inosine triphosphate was synthesized from [14C]hypoxanthine, but not from [14C]adenine or [14C]guanine. The metabolism of [14C]adenine and [14C]guanine was the same in erythrocytes that accumulated "normal" and "high" amounts of inosine triphosphate. Inosine triphosphate did not accumulate in leukocytes.

Adenine↗
PubMed1981

Activity of inosine triphosphate pyrophosphohydrolase in fresh and stored human erythrocytes.

The accumulation of inosine triphosphate (ITP) in human erythrocytes incubated with inosine depends on the activity of inosine triphosphate pyrophosphohydrolase (ITPH). High activity of this enzyme is accompanied by a low concentration of ITP and conversely. We showed that ITPH activity decreases with the prolongation of blood preservation time. As a consequence there is a lower accumulation of ITP in fresh erythrocytes incubated in a medium containing high concentrations of inosine, pyruvate and phosphate (IPP) than in red blood cells preserved at 4 degrees C. Synthesis of ITP in erythrocytes incubated in IPP medium being so intensive, it seems possible that during incubation an intermediate accumulates which decreases ITPH activity.

Blood Preservation↗
PubMed1977

Factors affecting inosinate synthesis and inosine triphosphate accumulation in human erythrocytes.

Measurements of rates of inosinate synthesis from radioactive hypoxanthine by human erythrocytes show a large degree of individual variation. Rates of inosinate synthesis also vary with the pH and phosphate concentration of the incubation medium. This may be due to changes in the rate of phosphoribosyl pyrophosphate synthesis, and the stimulatory effect of phosphate on this process seems to be more important than the inhibitory effect of 2,3-diphodphoglycerate. The rate of inosinate synthesis, and especially the extent of accumulation of inosine triphosphate, increase disproportionately with time of incubation up to at least 24 h. Storage of erythrocytes also tends to increase inosinate synthesis and inosine triphosphate accumulation.

Anaerobiosis↗
PubMed2001

Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene.

ITP and dITP exist in all cells. dITP is potentially mutagenic, and the levels of these nucleotides are controlled by inosine triphosphate pyrophosphatase (EC ). 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.

Amino Acid Sequence↗
PubMed2001

As to the clastogenic-, sister-chromatid exchange inducing-and cytotoxic activity of inosine triphosphate in cultures of human peripheral lymphocytes.

The influence of commercial inosine triphosphate (ITP) on the chromosome aberration rate, the mitotic rate, sister-chromatid exchange (SCE) frequency, and the proportion of first (X1), second (X2) and third (X3) division metaphases was investigated in 72h cultures of human peripheral lymphocytes. The blood donors had mild inactive arthrosis and a normal health check-up. All cultures of each volunteer were set-up simultaneously. In contrast to a previous report [Arch. Biochem. Biophys. 278 (1990) 238-244], it was demonstrated in two preliminary studies (number of subjects, n=5 each) that ITP at a final concentration of 100 microM does not induce chromosomal aberrations and, furthermore, that not ITP concentrations higher than 100 microM but ITP doses higher than 3.8mM prohibit culture growth. Based on these results, cultures with a final ITP concentration of 3.6mM (max.) and 1.8mM (max./2) were compared with control cultures (number of subjects n=10; three males and seven females, mean age x=57.6 years). Whereas no increase in the chromosomal breakage rate was observed in cultures with an ITP concentration of 1.8mM and only a marginally significant one (P=0.048) for 3.6mM ITP cultures, a highly significant induction of SCEs, not only at an ITP concentration of 3.6mM (P<0.0001) but also at 1.8mM (P<0.0001) was seen. The increase in the SCE frequency was not linear, but steeper from 0 to 1.8mM than from 1.8 to 3.6mM. Nevertheless, the difference between 1.8 and 3.6mM cultures was significant (P=0.027). The distribution of the number of SCEs per metaphase as well as the distribution of SCEs per chromosome correspond to the expected Poisson values. The investigation of the cytotoxic effect of the studied ITP concentrations revealed a highly significant reduction of the mitotic rate from 0 to 1.8mM as well as from 1.8 to 3.6mM in the aberration studies (all P values are equal to smallest possible one for a sample size of 10, namely, 0.002), and in the SCE studies there is a significant decrease in the X3 frequency when ITP is increased (0-1.8mM: P=0.0061 and 1.8-3.6mM: P<0.0001). The proportion of X1 within all X1 and X2 metaphases changes significantly only at the second dose step (0-1.8mM ITP: P=0.22 and 1.8-3.6mM ITP: P<0.0001). The results are discussed.

Cell Division↗
PubMed1990

Inosine triphosphate pyrophosphohydrolase deficiency in a kindred with adenosine deaminase deficiency.

A complete deficiency of inosine triphosphate pyrophosphohydrolase (ITPase) has been identified, together with high concentrations (mean 157 mumol/l) of the unusual nucleotide ITP, in the erythrocytes of 3 members of a consanguineous United Kingdom kindred. The defect has been noted previously in North America and Sweden, but even in presumed homozygotes some residual ITPase activity was reported. Homozygosity for the defect has not been associated previously with any clinical abnormality. In this kindred it was co-existent with adenosine deaminase (ADA) deficient severe combined immunodeficiency. Since the genes for both ITPase and ADA are localised on the same chromosome, segregation analysis of ITPase and ADA activity was undertaken in available kindred members. The results confirmed an autosomal recessive mode of inheritance for ITPase deficiency, but suggested that the co-existence with ADA deficiency was coincidental.

Adenosine Deaminase↗
PubMed1996

Force development with inosine triphosphate and uridine triphosphate in chemically skinned vascular smooth muscle.

The contraction of vascular smooth muscle is thought to be regulated by reversible phosphorylation of the 20,000 dalton light chains of myosin, catalyzed by myosin light chain kinase that is dependent on calcium and calmodulin. With phosphorylation, there is a coincident increase in the actin-activated myosin NTPase activity, cross bridge interaction and contractile activity. However, this myosin phosphorylation mechanism may not be the sole factor controlling actin-myosin interaction in vascular smooth muscle. Other mechanisms may function in addition to this myosin-linked regulation. A calcium-insensitive regulation of contraction was observed in helical strips of chemically skinned (Triton X-100) arterial smooth muscle. Millimolar concentrations of inosine triphosphate and uridine triphosphate supported concentration dependent force development in the absence of calcium. Force development was a function of the MgNTP concentration. At high free calcium concentrations, an additional component of force was observed. ITP and UTP, in contrast to ATP, are less effective substrates for the myosin light chain kinase, and their effect on actin-myosin interaction is thus less than that of ATP. They are, however, utilized by the myosin NTPase after treatment by ATP-gamma-S. The efficacy of the substrate for the activated NTPase is greater for UTP than ITP than for ATP.

Acid Anhydride Hydrolases↗
PubMed1981

Calcium ion-insensitive contraction of glycerinated porcine cardiac muscle fibers by Mg-inosine triphosphate. ITP as a tool to dissociate the contraction mechanism from the regulatory mechanism.

The contraction of cardiac muscle that has been treated with glycerol requires Ca2+ (pCa 8-5), when MgATP is used as a substrate. In contrast, this preparation contracts, even in the absence of Ca2+ (pCa 8-10), when ATP is replaced by ITP. Ca2+ dependency was not observed after increasing free Ca2+ concentrations from pCa 8.0 to 5.0, or after increasing MgITP concentration from 5 to 80 mM. On the other hand, rabbit skeletal muscle fiber treated by the same method as cardiac muscle demonstrates Ca2+ dependency in the presence of both MgITP and MgATP, although this Ca2+ regulation is less in the presence of MgITP. Loss of Ca2+ dependency was confirmed by the finding that, in contrast to ATPase, the ITPase activity of cardiac myofibrils was not dependent on Ca2+ concentrations. Furthermore, the very fast tension responses (quick phases) following quick stretch and quick release were missing in MgITP, and the contractions were similar to rigor. These were not rigor however, because phosphate liberation from ITP continued, and muscle shortening occurred in MgITP. These findings suggest that MgITP dissociates the contraction mechanism from the regulatory mechanism, modulating the regulatory properties of cardiac muscle fiber.

Adenosine Triphosphatases↗
PubMed1993

[Cyclic nucleotides and inosine triphosphate as biochemical modulators of receptor domain ion channel permeability].

Different pathways of control over the permeability of ionic channels in the receptor domains (RD) of biological membranes and their possible functional role in various receptor systems are discussed. It is suggested that cyclic mononucleotides and inositol-triphosphate may directly act as biochemical modulators of such permeability by blocking the Ca(2+)-binding sites of the gate mechanisms of RD ionic channels by recruiting, in particular, Ca2+ within the cell from both intracellular calcium depots and the intercellular medium. Kinetic schemes of gate mechanisms for all possible types of RD ionic channels have been proposed for a case when, in addition to Ca(2+)-ions, the reaction medium contains another type of ions or molecules capable of blocking only one Ca(2+)-binding site of the gate mechanism. Such kinetic schemes form the basis for qualitative and quantitative analyses of cyclic mononucleotide and inositol-triphosphate influence on the permeability of RD ionic channels.

Binding Sites↗