Dihydrofolate reductase

Dihydrofolate reductase is an enzyme that uses NADPH to reduce dihydrofolate to tetrahydrofolate. It sustains folate-dependent reactions needed for nucleotide synthesis and other cellular processes.

Folate cycle: A network of reactions that interconverts folate cofactors and transfers one-carbon units. Dihydrofolate reductase returns oxidized folate to the cofactor pool used throughout this cycle.
Methotrexate: An antifolate drug that inhibits dihydrofolate reductase and is used to treat cancers and autoimmune diseases. Its inhibition of the human enzyme limits folate-dependent nucleotide production.
Folate: A family of B vitamins and related cofactors that carry one-carbon units in metabolism. Dihydrofolate reductase recycles folate molecules within this broader family.
Bacterial dihydrofolate reductase: A bacterial enzyme that reduces dihydrofolate to tetrahydrofolate using NADPH. Its structure differs from the human enzyme in ways exploited by antibacterial inhibitors.
NADPH: A cellular electron carrier that supplies reducing power for biosynthesis and antioxidant defense. The enzyme draws electrons from NADPH to reduce dihydrofolate.
Trimethoprim: An antibacterial drug that selectively inhibits bacterial dihydrofolate reductase. Its preference for bacterial enzyme variants enables selective antimicrobial action.
Nucleotide biosynthesis: The cellular production of purine and pyrimidine building blocks for DNA and RNA. Reduced folates supply one-carbon units required for several nucleotide synthesis steps.
Human dihydrofolate reductase: The human enzyme that regenerates tetrahydrofolate from dihydrofolate. Its drug-binding properties contrast with those of microbial homologues.
Tetrahydrofolate: The reduced folate cofactor that carries one-carbon units in multiple metabolic reactions. It is the product whose regeneration gives the enzyme's reaction its metabolic value.
Pyrimethamine: An antiparasitic drug that inhibits dihydrofolate reductase in organisms such as Plasmodium. It targets parasite folate metabolism through inhibition of this enzyme.

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