DPYD
DPYD (dihydropyrimidine dehydrogenase, also known as DPD or DHPDHase) is a cytosolic flavoprotein oxidoreductase that catalyses the first and rate-limiting step of uracil and thymine catabolism. It also degrades the chemotherapeutic drug 5-fluorouracil. Browse Assay Genie's current range of DPYD research reagents below, or read on for the biology behind the target.
DPYD encodes dihydropyrimidine dehydrogenase, an NADP(+)-dependent enzyme that catalyses the reduction of uracil and thymine in the initial step of reductive pyrimidine catabolism. This pathway yields beta-alanine from uracil and beta-aminoisobutyrate from thymine. NCBI Gene describes the enzyme as the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. The enzyme is also capable of degrading the chemotherapeutic drug 5-fluorouracil, which links its activity directly to the handling of fluoropyrimidine drugs.
The DPYD gene sits at 1p21.3 and belongs to the dihydropyrimidine dehydrogenase family. In the HGNC classification it falls within the flavoproteins and oxidoreductases gene groups. UniProt places the DPYD protein in the cytosol. Two transcript variants encoding different isoforms have been reported for the gene. Orthologues are annotated in mouse and rat, both named Dpyd, which allows the enzyme to be studied in common rodent models.
Mutations in DPYD result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. For this reason the enzyme is of interest in pyrimidine metabolism, pharmacogenetics and oncology research. Researchers working with DPYD may use a DPYD antibody or a DPD ELISA kit to examine expression of the protein, alongside genetic analysis of the DPYD gene.
DPYD performs the initial, rate-limiting step in uracil and thymine breakdown, making it a central enzyme for studying pyrimidine turnover.
The enzyme degrades 5-fluorouracil, so its activity is relevant to how this chemotherapeutic drug is metabolised.
Reduced DPYD function is associated with an increased risk of toxicity in cancer patients receiving 5-fluorouracil.
Mutations in DPYD cause dihydropyrimidine dehydrogenase deficiency, a pyrimidine metabolism disorder linked to thymine-uraciluria.
DPYD catalyses the reduction of uracil and thymine in the first step of reductive pyrimidine catabolism, producing beta-alanine from uracil and beta-aminoisobutyrate from thymine. It is the rate-limiting enzyme of this pathway and can also degrade the chemotherapeutic drug 5-fluorouracil.
DPYD is also called DPD or DHPDHase, and its protein name is dihydropyrimidine dehydrogenase [NADP(+)]. The enzyme carries EC number 1.3.1.2. Two transcript variants encoding different isoforms have been identified for the gene, according to the NCBI Gene summary.
Mutations in DPYD cause dihydropyrimidine dehydrogenase deficiency, a pyrimidine metabolism error with thymine-uraciluria. Because the enzyme degrades 5-fluorouracil, deficiency is associated with an increased risk of toxicity in cancer patients receiving this chemotherapy. Mouse and rat Dpyd orthologues exist; check the datasheet of any product for its validated reactivity.
Other pyrimidine metabolism enzymes and fluoropyrimidine-pathway targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q12882; product specifications from Assay Genie datasheets.