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BIOCHEMICAL BACKGROUND OF TRIMETHOPRIM/SULPHAMETHOXAZOLE
Author(s) -
HITCHINGS GEORGE H.
Publication year - 1973
Publication title -
medical journal of australia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 131
eISSN - 1326-5377
pISSN - 0025-729X
DOI - 10.5694/j.1326-5377.1973.tb111178.x
Subject(s) - dihydrofolate reductase , trimethoprim , thymidylate synthase , folic acid , folic acid antagonists , enzyme , biochemistry , chemistry , microbiology and biotechnology , reductase , antibiotics , biology , medicine , chemotherapy , fluorouracil , genetics
In mammals, folic acid (FA), dihydrofolio acid (FAH,), and tetrahydrofolic acid (FAH 4 ), are assimilated from food. Microorganisms, on the other hand, synthesize FAH 4 de novo from p‐aminobenzoic acid. In all species, FAH 4 is reoxidized to FAH 2 in the synthesis of thymidylate, and the enzyme dihydrofolate reductase is essential to the maintenance of FAH4 pools. Various biosynthetic reactions vital to cellular growth and survival cannot take place if the pool of FAH 4 co‐factors falls below a critical level. Trimethoprim selectively inhibits microbial reductases, but its effectiveness is strikingly enhanced when the synthesis of FAH 2 is simultaneously blocked by sulphamethoxazole. Thus the combination of these two drugs has a broader spectrum, is more rapidly bactericidal, and is less susceptible to the development of resistance than either of the components.