Dihydropyrimidine dehydrogenase

The dihydropyrimidine dehydrogenase (DPD ) is an enzyme from the group of oxidoreductases, which catalyzes a step in the removal of endogenous pyrimidines such as uracil and thymine. In addition, it builds from various cytostatic agents such as 5- fluorouracil (5- FU) and capecitabine. An inherited disorder of DPD deficiency ( E79 according to ICD -10) leads to the fact that these cytotoxic drugs accumulate in cancer therapy in the body and can cause life-threatening poisoning. Blood tests for this genetic disease are commercially available.

Catalyzed reactions

NADPH / H NADP

Uracil is hydrogenated to dihydrouracil.

NADPH / H NADP

Thymine is hydrogenated to 5,6- Dihydrothymin.

The catalyzed reaction is reversible and rate-limiting, that is, depending on the availability of the starting materials and end products is an equilibrium. The enzyme is present in all eukaryotes, including the slime mold Dictyostelium, and many bacteria to be found. A close relative in plants is the dihydroorotate - reductase.

Importance and inhibition

In approximately 5 % of patients receiving 5 -fluorouracil as a cytostatic agent, were severe poisoning symptoms to cardiac arrhythmias. Chance of deaths have been reported. Reason for these reactions is a genetic, decreased activity of dihydropyrimidine dehydrogenase.

The enzyme is inhibited by various substances, including

  • Bromovinyluracil, a degradation product of Virostatikums brivudin ( therefore, co-administration of 5 -FU or its precursors and brivudin lead to dangerous interactions ),
  • Uracil,
  • Eniluracil.
Iron-sulfur cluster Human Genome Organisation Dihydrothymine Brivudine
240060
de