Dehalogenating and NADPH-modifying activities of dihydropyrimidine dehydrogenase.

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Dehalogenating and NADPH-modifying activities of dihydropyrimidine dehydrogenase.

Dihydropyrimidine dehydrogenase (DPDase) catalyzed the debromination of 5-bromo-5,6-dihydrouracil (BrUH2) to uracil at pH 7.7 and 37 degrees C. The debrominating activity of DPDase was increased 5-fold by treatment with H2O2, whereas the dehydrogenating activity was inhibited by this treatment. The time course for increasing the debrominating activity by H2O2 was similar to that for decreasing ...

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Familial Deficiency of Dihydropyrimidine Dehydrogenase

Severe neurotoxicity due to 5-fluorouracil (FUra) has previously been described in a patient with familial pyrimidinemia. We now report the biochemical basis for both the pyrimidinemia and neurotoxicity in a patient we have recently studied. After administration of a "test" dose of FUra (25 mg/m2, 600 gCi 16-3HJFUra by intravenous bolus) to a patient who had previously developed neurotoxicity a...

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Regulation of dihydropyrimidine dehydrogenase in colorectal cancer.

Dihydropyrimidine dehydrogenase (DPD) is responsible for degradation of the pyrimidines uracil and thymine and the inactivation of the chemotherapeutic agent 5-fluorouracil. DPD activity is highly variable in cancer populations, and this variation may influence the antitumor efficacy of 5-fluorouracil. However, little is known about the regulation of DPD mRNA expression in any tissues. Using a ...

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Clinical implications of dihydropyrimidine dehydrogenase inhibition.

Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). DPD has an important role in regulating the availability of 5-FU for anabolism. It is now clear that DPD also accounts for much of the variability observed with the therapeutic use of 5-FU, including variable drug levels during 24-hour infusion, erratic pharmacokinetics, variab...

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Purification and characterization of dihydropyrimidine dehydrogenase from human liver.

Although dihydropyrimidine dehydrogenase has been purified to varying degrees from several species, very little is known about the human enzyme. The importance of this enzyme has recently been shown with cancer chemotherapy, particularly in patients with genetic deficiency of this enzyme. In the present study, this enzyme was purified 7800-fold to homogeneity from human liver by introducing sev...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1994

ISSN: 0021-9258

DOI: 10.1016/s0021-9258(19)51065-1