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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