Background: The pharmacogenetic-oriented approach reduces the toxicity and increases the safety of chemotherapeutic agents. 6-mercaptopurin (6-MP) metabolizing enzymes such as thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) contribute to variable responses and adverse effects among leukemia patients treated with 6-MP. The aim of our study was to identify th...

Marine mammals are exposed to ischemia/reperfusion and hypoxia/reoxygenation during diving. During oxygen deprivation, adenosine triphosphate (ATP) breakdown implies purine metabolite accumulation, which in humans is associated with pathological conditions. Purine recycling in seals increases in response to prolonged fasting and ischemia. Concentrations of metabolites and activities of key enzy...

A novel process is presented for the detection of known mutations and polymorphisms in DNA. This process, termed glycosylase mediated polymorphism detection (GMPD) involves amplification of the target DNA using three normal dNTPs and a fourth modified dNTP, whose base is a substrate for a specific DNA-glycosylase once incorporated into the DNA. The work described here utilises uracil DNA-glycos...

Comparative kinetic studies at pH 6.8, 7.3, and 8.0 reveal that the phosphoenolpyruvate carboxykinase-catalyzed inosine trlphosphate-dependent oxalacetate-H14C0sexchange is much more rapid than either the over-all decarboxylation or carboxylation reactions. At pH 6.8, the relative carboxylation, decarboxylation, and oxalacetate-H14C03exchange rates are 1.0, 8.3, and 30, respectively. While the ...

Sanitization of the cellular nucleotide pools from mutagenic base analogues is necessary for the accuracy of transcription and replication of genetic material and plays a substantial role in cancer prevention. The undesirable mutagenic, recombinogenic, and toxic incorporation of purine base analogues [i.e., ITP, dITP, XTP, dXTP, or 6-hydroxylaminopurine (HAP) deoxynucleoside triphosphate] into ...

The nucleotide selectivities of the human P2Y(4) (hP2Y(4)) and rat P2Y(4) (rP2Y(4)) receptor stably expressed in 1321N1 human astrocytoma cells were determined by measuring increases in intracellular [Ca(2+)] under conditions that minimized metabolism, bioconversion, and endogenous nucleotide release. In cells expressing the hP2Y(4) receptor, UTP, GTP, and ITP all increased intracellular [Ca(2+...

We have selected from a mixture of random polynucleotides an RNA that is able to replicate in the presence of the DNA-dependent RNA polymerase of Escherichia coli, provided the medium contains Mn(2+) and ITP, in addition to ATP, CTP, and UTP. The RNA consists of a chain of about 125 (+/-25) nucleotides and appears to have a defined, nonrepetitive sequence.

When ATP, the normal phosphate donor for hexokinase D ('glucokinase'), is replaced by ITP, the positive co-operativity with respect to glucose disappears. This may be rationalized in relation to kinetic models for hexokinase D co-operativity, which assume that with the normal substrates the chemical reaction and subsequent release of products occur so rapidly that binding of substrates cannot a...