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Updated: Aug 6, 2026
08:36
Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues
Published on: May 26, 2018
[Dihydropyrimidine dehydrogenase activity and its genetic aberrations]
1Dept. of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science.
Gan to Kagaku Ryoho. Cancer & Chemotherapy
|August 17, 2006
Summary
Dihydropyrimidine dehydrogenase (DPD) deficiency significantly increases the risk of severe toxicity from the chemotherapy drug 5-fluorouracil (5-FU). Phenotyping is crucial for identifying DPD deficiency before 5-FU treatment, as genotyping is often insufficient.
Area of Science:
- Biochemistry: Focuses on the enzymatic activity of Dihydropyrimidine dehydrogenase (DPD) in pyrimidine metabolism.
- Pharmacology: Investigates the metabolic degradation of the anti-cancer drug 5-fluorouracil (5-FU) by DPD.
- Genetics: Explores the DPYD gene variants associated with DPD activity and deficiency.
Context:
- Dihydropyrimidine dehydrogenase (DPD) is essential for metabolizing pyrimidine bases and the chemotherapy drug 5-fluorouracil (5-FU).
- DPD deficiency is linked to severe or lethal toxicity in patients receiving 5-FU chemotherapy.
- Significant variations in DPD activity exist within the population, with deficiency rates estimated at 3-5% for partial and 0.1% for complete deficiency.
Purpose:
- To highlight the critical role of DPD in 5-FU chemotherapy and the clinical significance of DPD deficiency.
- To evaluate the incidence of DPD deficiency through population studies.
- To emphasize the limitations of genotyping for identifying DPD deficiency and advocate for phenotyping.
Summary:
- DPD is the primary enzyme responsible for the catabolism of 5-FU, with over 85% of the drug being processed by it.
- Severe toxicity is observed in cancer patients with low or deficient DPD activity, underscoring its clinical importance.
- Population studies reveal a notable frequency of DPD deficiency, necessitating reliable methods for its identification.
- Genotyping alone is insufficient to identify DPD deficiency in all affected patients, as only 17% have identifiable DPYD variants.
- Phenotyping is proposed as a more effective method for identifying DPD deficiency prior to 5-FU administration.
Impact:
- Establishes the necessity of assessing DPD activity before initiating 5-FU chemotherapy to mitigate severe adverse events.
- Informs clinical practice by recommending phenotyping over genotyping for accurate DPD deficiency diagnosis.
- Contributes to personalized cancer treatment strategies by enabling risk stratification based on DPD status.
- Highlights the complex genetic and molecular factors influencing DPD activity in vivo.
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