development of a detection method using 2'-fluoro-beta-alanine derivatization with o-phthalaldehyde at room temperature and mass spectrometric analysis by the liquid chromatography-mass spectrometry-electrospray ionization system, method evaluation and optimization, overview
pyrimidine binding to this enzyme is accompanied by active site loop closure that positions a catalytically crucial cysteine 671 residue. The deprotonation of the loop residue H673 is required for active site closure, while S670 is important for substrate recognition. R235 is crucial for FAD binding
the first FeS cluster, with unusual coordination, cannot be reduced and displays no activity when Q156 is mutated to glutamate. The active site loop comprising residues 670-683 are observed in open and closed conformational states, overview
the N-terminal half of DPD is a member of a family of FAD-containing NADPH oxidoreductases, which transfer electrons to an acceptor protein or domain through [4Fe-4S] clusters of low to very low potential
in mammals, the pyrimidines uracil and thymine are metabolised by a three-step reductive degradation pathway. Dihydropyrimidine dehydrogenase catalyses its first and rate-limiting step, reducing uracil and thymine to the corresponding 5,6-dihydropyrimidines in an NADPH-dependent reaction
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cocrystallization with 5-iodouracil 1 mM and NADPH 5 mM, ternary complex in 100 mM HEPES, pH 7.5, 22% polyethylene glycol 6000, uracil-4-acetic acid 1 mM, structure determination at different pH-values
natural mutation identified in a human with complete loss of enzymic activity. Crystallization data of Sus scrofa recombinant mutant, mutation might prevent binding of the prosthetic group FMN and affect folding of the enzyme protein
natural mutation identified in a human with complete loss of enzymic activity. Crystallization data of Sus scrofa recombinant mutant, mutation interferes with the electron flow between NADPH and the pyrimidine binding site of the enzyme
study on DPD enzyme expression using RT-PCR, immunohistochemistry, enzymatic activity and ELISA. Highest correlation is observed between protein expression measured by ELISA and enzyme activity, correlation of gene expression and ELISA is also significant
development of a HPLC method, sufficient, accurate, fast and sensitive to be applied to the analysis of 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in plasma and cytoplasmic samples, allowing accurate pharmacokinetic analyses and measurements of dihydropyrimidine dehydrogenase in patients who are candidates for fluoropyrimidine-based chemotherapy without the need of a labeled substrate for enzyme studies
identification of mutants G366A and T768K in healthy Japanese volunteers. G366A results in marked decrease in enzyme affinity to NADPH, reduction of Vmax for 5-fluorouracil degrading activity, T768K leads to rapid loss of enzyme activity
uracil breath test breath 13CO2 pharmacokinetics parallel plasma [2-13C]uracil and [2-13C]dihydrouracil pharmacokinetics and are an accurate measure of interindividual variation in enzyme activity. Data support the use of uracil breath test to identify enzyme deficiency before 5-fluorouracil-based therapy
Di Paolo, A.; Danesi, R.; Ciofi, L.; Vannozzi, F.; Bocci, G.; Lastella, M.; Amatori, F.; Martelloni, B.M.; Ibrahim, T.; Amadori, D.; Falcone, A.; Del Tacca, M.
Improved analysis of 5-Fluorouracil and 5,6-dihydro-5-Fluorouracil by HPLC with diode array detection for determination of cellular dihydropyrimidine dehydrogenase activity and pharmacokinetic profiling