unreviewed

Dihydrofolate reductase (DHFR)

3 reactions · 3 pathways

Cofactors used

NADP+ · B3 (Niacin) NADPH · B3 (Niacin) THF (folate) · B9 (Folate)

Clinical / pharmacological. Target of methotrexate, trimethoprim, pyrimethamine

What it does, reaction by reaction

3 reactions

One-Carbon Metabolism (Folate Cycle) Amino Acid & Nitrogen Metabolism · Cytosol + mitochondrion

step 1 Irreversible

Dihydrofolate (DHF) + NADPH + H⁺ → tetrahydrofolate (THF) + NADP⁺

Converts Dihydrofolate (DHF) NADPH H+ into Tetrahydrofolate (THF) NADP+

› Notes

Dihydrofolate reductase (DHFR) regenerates reduced THF after DHF is produced by thymidylate synthase. NADPH is required; this is an essential, effectively irreversible reductive regeneration step and the pharmacologic target of methotrexate, trimethoprim, and pyrimethamine.

Deoxyribonucleotide Formation (Ribonucleotide Reductase pathway and thymidylate synthesis) Nucleotide Metabolism · Cytosol

step 7 Irreversible/directional

DHF → THF

Converts Dihydrofolate (DHF) into Tetrahydrofolate (THF)

› Notes

DHFR catalyzes DHF + NADPH + H+ → THF + NADP+. This reaction regenerates reduced folate after every thymidylate synthase turnover and is essential to maintain dTMP synthesis.

Pyrimidine De Novo Synthesis (through to UMP, then CTP/dTMP) Nucleotide Metabolism · Cytosol (one mitochondrial step)

step 14 Irreversible/directional

DHF → THF; THF → 5,10-methylene-THF

Converts Dihydrofolate (DHF) into Tetrahydrofolate (THF)

› Notes

Dihydrofolate reductase (DHFR) regenerates THF: DHF + NADPH + H+ → THF + NADP+. Serine hydroxymethyltransferase then catalyzes THF + serine ⇌ 5,10-methylene-THF + glycine, using pyridoxal phosphate; this restores the one-carbon donor required by thymidylate synthase.

Showing all 3 reactions.

What accelerates and inhibits it

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

1 entries

Deoxyribonucleotide Formation (Ribonucleotide Reductase pathway and thymidylate synthesis)

Listed there as: Dihydrofolate reductase

Accelerated by

DHF and NADPH availability

Inhibited by

Methotrexate, trimethoprim (much greater selectivity for microbial DHFR), pemetrexed

Hormonal control

Proliferation-associated transcriptional induction; no canonical acute hormonal allosteric regulator.

Recent literature

Load 10 most recent

Nothing is fetched until you ask, so the page stays fast and the request is yours rather than automatic.

Europe PMC · ten most recent, newest first