Dihydropyrimidinase (DPYS)

Dihydropyrimidinase (DPYS) is a cytosolic zinc metalloenzyme that catalyzes the reversible ring opening of 5,6-dihydrouracil and 5,6-dihydrothymine to N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyrate, respectively, representing the second step of the reductive degradation of pyrimidines in the nucleotide catabolic pathway[1][3][5]. It is highly expressed in the liver and kidney. Mutations in the DPYS gene cause dihydropyrimidinase deficiency, an autosomal recessive disorder that can result in elevated pyrimidine metabolites and a spectrum of clinical symptoms ranging from asymptomatic to severe neurodevelopmental disorders such as infantile spasms, brain atrophy, and developmental delay[2][3]. DPYS is indirectly relevant to chemotherapy with 5-fluorouracil, as impaired pyrimidine degradation can precipitate severe drug toxicity[2].

Other names

DHPDHPaseDihydropyrimidine amidohydrolaseHydantoinase

Enzymatic hydrolysis of 5,6-dihydrouracil and 5,6-dihydrothymine ring opening in pyrimidine degradation[1][2][5]