dihydrouracil

Dihydrouracil is a saturated derivative of the pyrimidine uracil and a normal intermediate in the catabolism of pyrimidines. It is formed when uracil is reduced by the enzyme dihydropyrimidine dehydrogenase (DPD), a cytosolic flavoprotein that catalyzes the first step in the breakdown of uracil and thymine. The resulting dihydrouracil is subsequently metabolized by dihydropyrimidinase and related enzymes into downstream metabolites such as β-alanine and other related products. Dihydrouracil is one of several pyrimidine metabolites produced during routine nucleotide turnover.

In humans, dihydrouracil is normally present in body fluids at trace levels as part of ongoing pyrimidine metabolism. It can be detected in plasma and urine and is often assayed together with uracil to assess pyrimidine clearance.

Clinical significance of dihydrouracil centers on dihydropyrimidine dehydrogenase deficiency, an inherited condition that impairs the reduction of uracil and thymine. Individuals with DPD deficiency may experience severe toxicity if treated with fluoropyrimidine chemotherapies such as 5-fluorouracil or capecitabine, due to impaired drug catabolism. As a result, measurement of uracil and dihydrouracil levels in plasma or urine, and the ratio between these metabolites, is used to screen for DPD deficiency prior to chemotherapy in some guidelines. Genetic testing of DPYD variants is another approach to assess risk.

Chemical data commonly cited for dihydrouracil include its formula, C4H6N2O2, and its status as a dihydro derivative of uracil.