Dehalogenating and NADPH-modifying activities of dihydropyrimidine dehydrogenase.

摘要: 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 DPDase was increased 5-fold by treatment with H2O2, whereas dehydrogenating inhibited this treatment. time course for increasing H2O2 similar that decreasing activity. Thus, relative amounts activities were reciprocally related. decreased number thiol groups reactive 5,5'-dithiobis(2-nitrobenzoate) from eight/subunit less than one. kcat BrUH2 H2O2-treated (OxDPDase) 1.9 s-1, which comparable reduction thymine (2.1 s-1) DPDase. Even though does not involve a net BrUH2, NADPH required reaction OxDPDase 5-iodo-5,6-dihydrouracil (IUH2) more complicated BrUH2. Aerobically, deiodination IUH2 iodination 5-iodo-6-hydroxy-1,4,6-trihydronicotinamide adenine dinucleotide phosphate. turnover enhanced NaI had value 3.5 s-1 in presence 4 mM 50 NaI. Anaerobically, above reactions, 5,6-dihydrouracil, hydration 6-hydroxy-1,2,3,4-tetrahydronicotinamide anaerobic aerobic NADPH.