In order to characterize a step in the reaction sequence of sodium and potassium ion-dependent adenosine triphosphatase (EC 3.6.1.3), the binding of radioactive adenosine triphosphate to kidney cell membranes was estimated by flow dialysis in the presence of a chelator of divalent cations, which prevented hydrolysis of the adenosine triphosphate. Adenosine triphosphate was bound to a single sit...

The hyperthermophilic bacterium Thermotoga maritima has a noncanonical nucleoside triphosphatase that catalyzes the conversion of inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) and xanthosine triphosphate (XTP) into inosine monophosphate (IMP), deoxyinosine monophosphate (IMP) and xanthosine monophosphate (XMP), respectively. The k(cat)/K(m) values determined at 323 and 353 K fall...

Understanding individual variation is fundamental to personalized medicine. Yet interpreting complex phenotype data, such as multi-compartment metabolomic profiles, in the context of genotype data for an individual is complicated by interactions within and between cells and remains an unresolved challenge. Here, we constructed multi-omic, data-driven, personalized whole-cell kinetic models of e...

Inosine triphosphatase (ITPase) is one of the enzymes involved in thiopurine metabolism. Polymorphisms in the ITPA gene, resulting in a decreased activity of ITPase, are associated with adverse drug reactions during thiopurine therapy. Measuring ITPase activity is therefore of utmost importance. We compared measurement of ITPase activity in fresh erythrocyte lysates and eluates of dried blood s...

Mammalian inosine triphosphatase encoded by ITPA gene hydrolyzes ITP and dITP to monophosphates, avoiding their deleterious effects. Itpa(-) mice exhibited perinatal lethality, and significantly higher levels of inosine in cellular RNA and deoxyinosine in nuclear DNA were detected in Itpa(-) embryos than in wild-type embryos. Therefore, we examined the effects of ITPA deficiency on mouse embryo...

Mizoribine monophosphate (MZP) is a specific inhibitor of the cellular inosine-5'-monophosphate dehydrogenase (IMPDH), the enzyme catalyzing the rate-limiting step of de novo guanine nucleotide biosynthesis. MZP is a highly potent antagonistic inhibitor of IMPDH that blocks the proliferation of T and B lymphocytes that use the de novo pathway of guanine nucleotide synthesis almost exclusively. ...

The Mg chelates of ITP, GTP, and UTP in addition to that of ATP were shown to be capable of causing complete relaxation of myofibrils as indicated by the complete inhibition of syneresis and the reduction of the NTPase activity to that of isolated myosin. For ITP and GTP the required concentrations were about 100 times higher than those for ATP, whereas UTP was maximally effective also in low c...

5'-O-(4-fluorosulphonylbenzoyl)-esters of ribavirin (FSBR), adenosine (FSBA), guanosine (FSBG) and inosine (FSBI) were obtained by acylation of the 5'-OH of adenosine, guanosine, inosine, and ribavirin with 4-fluorosulphonylbenzoyl chloride (FSBCI) in HMPA. The above derivatives were tested as inhibitors of nucleoside triphosphatase (NTPase)/helicase activities of Flaviviridae: hepatitis C viru...