The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene 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. Two transcript variants encoding different isoforms have been found for this gene. In humans the enzyme is encoded by the DPYD gene. It is the initial and rate-limiting step in pyrimidine catabolism.[citation needed] It catalyzes the reduction of uracil and thymine. It is also involved in the degradation of the chemotherapeutic drugs 5-fluorouracil and tegafur. It also participates in beta-alanine metabolism and pantothenate and coa biosynthesis. The protein is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Genetic deficiency of this enzyme results in an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy.
Background References
1. Henricks LM. et. al. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol. 2018 Nov
2. Wigle TJ. et. al. DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report. Pharmaceutics. 2019 May
Sequence Similarity
Belongs to the dihydropyrimidine dehydrogenase family.
Tissue Specificity
Found in most tissues with greatest activity found in liver and peripheral blood mononuclear cells.
Western blot analysis of DPYD on THP-1 (Human acute monoblastic leukemia cell) cell lysate with Rabbit anti-DPYD antibody (ET7110-83) at 1/1,000 dilution.
Lysates/proteins at 10 µg/Lane. Exposure time: 3 minutes; ECL: K1801
Blocking: 5% NFDM/TBST, 1 hour at room temperature Primary antibody: ET7110-83, 1/1,000 in 5% NFDM/TBST, 2 hours at room temperature Secondary antibody: Goat anti-Rabbit IgG-HRP (HA1001), 1/50,000 in 5% NFDM/TBST, 1 hour at room temperature
Predicted band size: 111 kDa Observed band size: 111 kDa
Immunohistochemical analysis of paraffin-embedded human liver tissue with Rabbit anti-DPYD antibody (ET7110-83) at 1/200 dilution.
The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET7110-83) at 1/200 dilution for 0.5 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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