Dihydropyrimidinase catalyzes the reversible cyclization of dihydrouracil
to N-carbamoyl-[beta]-alanine in the second step of the pyrimidine degradation pathway (Figure 1).
The catabolism of C14-labeled uracil, dihydrouracil
, and beta-ureidopropionic acid in rat liver slices.
The drug undergoes catabolism primarily in the liver by reduction of the pyrimidine ring by enzymatic action of dihydrouracil
We purchased the following compounds from Sigma: adenine, adenosine, 2-deoxyadenosine, 2-deoxyguanosine, inosine, 2-deoxyinosine, xanthine, hypoxanthine, orotic acid, uric acid, thymine, uracil, dihydrothymine, dihydrouracil, N-carbamyl-[beta]-aminoisobutyric acid, N-carbamyl-[beta]-alanine, thymidine, uridine, pseudouracil, 5-hydroxymethyluracil, and 2-deoxyuridine.
Optimal peak shapes were achieved for all analytes except for dihydrouracil and N-carbamyl-[beta]-alanine, which were characterized by broader and split peaks.
For xanthine, adenosine, 2,8-dihydroxyadenine, uracil, thymine, dihydrouracil, dihydrothymine, N-carbamyl-[beta]-amino-isobutyric acid, N-carbamyl-[beta]-alanine, uridine, and pseudouridine, the detection limit was between 1 and 10 [micro]mol/L.
In the ion source, 5,6-dihydrouridine ([[M + H].sup.+] = m/z 247) is partly degraded to m/z 115, which is identical to the [[M + H].sup.+] ion of dihydrouracil. Because 5,6-dihydrouridine coelutes with dihydrouracil, it contributes substantially to the transition peak attributed to dihydrouracil.
Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: a potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage.
Simple liquid chromatographic method for the determination of uracil and dihydrouracil plasma levels: a potential pretreatment predictor of 5-fluorouracil toxicity.
Catabolism of the pyrimidine bases thymine and uracil consists of three consecutive steps: (a) thymine and uracil are catabolized by dihydropyrimidine dehydrogenase (DPD; EC 184.108.40.206)  to dihydrothymine (DHT) and dihydrouracil (DHU), respectively; (b) DHT is converted to N-carbamyl-[beta]-aminoisobutyric acid (N-C-[beta]-AlB) and DHU to N-carbamyl-[beta]-alanine (N-C-(3-Ala) by dihydropyrimidinase (DHP, EC 220.127.116.11); and (c) ([beta]-ureidopropionase (([beta]-UP; EC 18.104.22.168) catalyzes the last step in pyrimidine degradation by converting N-C-[beta]-AIB to ([beta]-aminoisobutyric acid and N-C-[beta]-Ala to ([beta]-alanine.
 Nonstandard abbreviations: DPD, dihydropyrimidine dehydrogenase; DHT, dihydrothymine; DHU, dihydrouracil; N-C-[beta]-AIB, N-carbamyl-[beta]-aminoisobutyric acid; N-C-[beta]-Ala, N-carbamyl-[beta]-alanine; [beta]-UP, [beta]-ureidopropionase; 5FU, 5-fluorouracil; ESI, electrospray ionization; MS/MS, tandem mass spectrometry; and IS, internal standard.
dehydrogenase activity in normal, differentiating and regenerating liver and in hepatomas.