Human UMP/CMP kinase (cytidylate kinase; EC 2.7.4.14) is responsible for phosphorylation of CMP, UMP, and deoxycytidine monophosphate (dCMP) and also plays an important role in the activation of pyrimidine analogs, some of which are clinically useful anticancer or antiviral drugs. Previous kinetic data using recombinant or highly purified human UMP/CMP kinase showed that dCMP, as well as pyrimi...

Bacterial UMP kinases are essential enzymes involved in the multistep synthesis of nucleoside triphosphates. They are hexamers regulated by the allosteric activator GTP and inhibited by UTP. We solved the crystal structure of Escherichia coli UMP kinase bound to the UMP substrate (2.3 A resolution), the UDP product (2.6 A), or UTP (2.45 A). The monomer fold, unrelated to that of other nucleosid...

A linked-function analysis of the allosteric responsiveness of carbamoyl phosphate synthetase (CPS) from E. coli was performed by following the ATP synthesis reaction at low carbamoyl phosphate concentration. All three allosteric ligands, ornithine, UMP, and IMP, act by modifying the affinity of CPS for the substrate MgADP. Individually ornithine strongly promotes, and UMP strongly antagonizes,...

The Uncertainty Modeling Process for Semantic Technologies (UMP-ST) is an incremental and iterative approach that covers the difficulty in maintaining and evolving existing POs [5]. It is a general methodology for the majority of the existing semantic technologies which support uncertainty. One of them is the Probabilistic OWL (PR-OWL), which is a language for representing Multi-Entity Bayesian...

The biosynthesis of brain membrane phosphatides, e.g., phosphatidylcholine (PtdCho), may utilize three circulating compounds: choline, uridine (a precursor for UTP, CTP, and CDP-choline), and a PUFA (e.g., docosahexaenoic acid); moreover, oral administration of the uridine source uridine-5'-monophosphate (UMP) can significantly increase levels of the phosphatides throughout the rodent brain. Si...

We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and ...

An enzyme preparation from rabbit muscle catalyzes the incorporation of uridine monophosphate into the terminal nucleotide sequence of yeast amino acid transfer ribonucleic acid. Reactants are UTP, Mg++, and transfer RNA which has been partially digested with snake venom phosphodiesterase. Some characteristics of the incorporation system are presented. Incorporation of UMP into tranfer RNA rath...

To investigate the mechanism by which 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAr) induces apoptosis in multiple myeloma cells, we conducted an unbiased metabolomics screen. AICAr had selective effects on nucleotide metabolism, resulting in an increase in purine metabolites and a decrease in pyrimidine metabolites. The most striking abnormality was a 26-fold increase in orotate associate...

3 Running Title: Pyrimidine starvation in multiple myeloma cells Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. ABSTRACT To investigate the mechanism by which AICAr induces apoptosis in multiple myeloma (MM) cells, we performed an unbiased metabolomics screen. AICAr had selective effects on nucleotide metabolism, resulting in an increase in...