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rate-limiting unreviewed

Dihydropyrimidine dehydrogenase (DPD)

2 reactions · 1 pathways

Cofactors used

NADP+ · B3 (Niacin) NADPH · B3 (Niacin)

Clinical / pharmacological. DPD deficiency: severe 5-fluorouracil toxicity

What it does, reaction by reaction

2 reactions

Pyrimidine Degradation Nucleotide Metabolism · Cytosol

step 6 Irreversible/directional rate-limiting

Uracil → 5,6-dihydrouracil

Converts Uracil into 5,6-Dihydrouracil

› Notes

DPD catalyzes uracil + NADPH + H+ → 5,6-dihydrouracil + NADP+. DPD is a large flavoprotein/iron-sulfur enzyme requiring FAD, FMN, and NADPH; this NADPH-dependent reduction is the rate-limiting step of pyrimidine degradation.

step 7 Irreversible/directional rate-limiting

Thymine → 5,6-dihydrothymine

Converts Thymine into 5,6-Dihydrothymine

› Notes

DPD catalyzes thymine + NADPH + H+ → 5,6-dihydrothymine + NADP+. The same rate-limiting enzyme handles both major pyrimidine bases.

Showing all 2 reactions.

What accelerates and inhibits it

Regulation is pathway-specific, so each context is listed separately

1 entries

Pyrimidine Degradation

Accelerated by

Uracil/thymine availability; adequate NADPH

Inhibited by

5-ethynyluracil and pharmacologic DPD inhibitors; genetic deficiency markedly lowers activity

Hormonal control

No major direct hormonal regulation; expression/activity vary substantially among individuals and tissues.

Recent literature

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Europe PMC · from cache · sorted by publication date

  1. 1
    Exploring the gut microbiome and metabolomic interactions of antimetabolite drugs to optimize therapy.

    Chen J, Wang Y, Xu L, Li X, Zhao L. · 2026-02-27

    open access unreviewed
  2. 2
    DPYD polymorphisms in Native populations from the Brazilian Amazon: the absence of the variants in currently recommended clinical genotyping panels.

    Suarez-Kurtz G, Basta PC, Perini JA. · 2026-06-23

    unreviewed
  3. 3
    Pharmacogenomic and Drug Interactions Risk in Cardio-Oncology: A precision medicine perspective for India.

    Verma A, D P. · 2026-08-12

    unreviewed
  4. 4
    Long-term storage stability of uracil in plasma.

    Kirkeby MH, Hoffmann-Lücke E, Greibe E. · 2026-08-12

    unreviewed
  5. 5
    Breast Cancer in Sudan: The Need for Pharmacogenomics Research and Its Implications for African Precision Medicine.

    Elhaj KEM, Mudawi MME. · 2026-08-07

    unreviewed
  6. 6
    <i>DPYD</i>-Guided Dosing of Metronomic Capecitabine Plus Vinorelbine in Metastatic Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: A Real-World Retrospective Study.

    Schettini F, Membrino A, Di Grazia G, Caltavituro A, Strina C, Milani M, Impeduglia A, Paganini L, Bosi A, Te… · 2026-08-07

    unreviewed
  7. 7
    Pharmacogenomic biomarkers in oncology: evidence, clinical utility, and barriers to implementation.

    Vishwash SK, Soni RB, Kosey S, Sood R. · 2026-08-06

    unreviewed
  8. 8
    A rare variant in DPYD c.812delT causes severe adverse events of S-1 in a patient with tongue cancer.

    Ishimura H, Suehiro A, Hira D, Hishinuma E, Kato M, Maekawa M, Yasuda T, Katsube Y, Katada Y, Imayoshi N, Shi… · 2026-08-03

    unreviewed
  9. 9
    Dihydropyrimidine Dehydrogenase Testing: From Pharmacogenomics to Equitable Practice.

    Gaddy JJ, Kunz PL, Sundar R. · 2026-08-01

    unreviewed
  10. 10
    Dabupi decoction mitigates fluorouracil-induced intestinal mucositis via farnesoid X receptor activation and dihydropyrimidine dehydrogenase upregulation.

    Wang S, Li Y, Ma J, Li J, Huang D, Wa X, Zhou Y, Liu Y. · 2026-04-30

    unreviewed

External claims. These come from an index outside this database and are not checked against it. Treat them as leads.