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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

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Europe PMC · fetched just now · sorted by publication date

  1. 1
    Experimental and computational analysis of glycan processing at increased monoclonal antibody productivities.

    Pranomphon R, Gialamoidou S, Yamabhai M, Sharfstein ST, Jiménez Del Val I. · 2026-07-20

    unreviewed
  2. 2
    Design, synthesis, and antibacterial activity study of pyrroloquinazoline diamine derivatives.

    Cheng M, Tian Y, Shang J, He W, Zheng Y, Yan C, Chen X, Li J, Jiang Y, Fu Q, Deng X, Xiao X, Song M. · 2026-06-24

    open access unreviewed
  3. 3
    MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.

    Kisielewska M, Suwała S, Drąg-Zalesińska M, Rembiałkowska N. · 2026-06-15

    open access unreviewed
  4. 4
    Integration of nuclear mechanosensing with integrin-extracellular matrix adhesions.

    Sandria S, King MC. · 2026-05-28

    open access unreviewed
  5. 5
    Comment on "sharp rise in high-virulence <i>Bordetella pertussis</i> with macrolides resistance in Northern China".

    Li Z, Li Z, Ma X. · 2026-04-27

    open access unreviewed
  6. 6
    <i>Toxoplasma gondii</i> effector GRA35 mediates neuronal damage <i>via</i> ER stress and mitochondria-associated apoptosis.

    Wang J, Chen Y, Zhou N, Li F, Dai N, Chen Z, Liu S, An R, Chen L, Du J. · 2026-04-10

    cited 1× open access unreviewed
  7. 7
    Interactions between nutrition and the epigenome: how can it be harnessed for public health?

    Anastasopoulou M, Dereki I, Sgourou A, Lagoumintzis G. · 2026-03-12

    open access unreviewed
  8. 8
    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
  9. 9
    Metabolomic profiling of neat uterine luminal fluid in cows: local enrichment and nutritional modulation.

    Sagheer M, Hoorn QA, Maldonado MB, Schalich KM, Ashrafi N, A Mimi R, Graham SF, Selvaraj V, Hansen PJ. · 2026-01-07

    cited 3× open access unreviewed
  10. 10
    In-vitro, in-vivo, and in-silico investigation of the traditionally used polyherbal combinations of Coptis teeta, Nyctanthes arbor-tristis, and Andrographis paniculata.

    Tayeng D, Nath D, Sarma M, Roy D, Gogoi N, Chetia D, Zothantluanga JH. · 2026-06-11

    unreviewed

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