Dihydrofolate reductase and Dihydropteroate synthase (DHFR (Dihydrofolate reductase), DHPS (Dihydropteroate synthase))

Dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are enzymes essential for folate metabolism. DHFR reduces dihydrofolic acid to tetrahydrofolic acid, a key intermediate required for nucleotide biosynthesis and cell proliferation. DHPS catalyzes the formation of dihydropteroate, a precursor in folate synthesis found in microorganisms but not humans[1][2][3][7]. Both are targeted by antimicrobial agents: sulfonamides inhibit DHPS, and trimethoprim/pyrimethamine inhibit DHFR, often used in combination for synergistic effects and to delay resistance emergence in pathogens such as Plasmodium falciparum (malaria)[6][7]. In human medicine, DHFR is also a target for anticancer drugs (e.g. methotrexate)[1]. Resistance due to gene mutations is a major therapeutic challenge, especially in infectious disease contexts[5][6].

Other names

DHFR (Dihydrofolate reductase)DHPS (Dihydropteroate synthase)Dihydropteroate synthetase

DHFR inhibitors block reduction of dihydrofolate to tetrahydrofolate, preventing synthesis of purines and thymidylate DHPS inhibitors block folate biosynthesis by competing with para-aminobenzoic acid (pABA) for binding, thus blocking dihydropteroate formation Dual inhibition leads to synergistic blockade of folate metabolism