Study note
BiochemistryMicronutrients: Vitamins & Minerals

Folate metabolism in DNA synthesis and drug action

THE CONTEXT
Folate-dependent thymidine synthesis and folate regeneration provide targets for cancer chemotherapy and antimicrobial drugs.

Thymidine synthesis and folate regeneration

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Thymidylate synthase catalyzes methylation of deoxyuridine monophosphate (dUMP) to thymidine monophosphate (TMP), an essential step for DNA synthesis.
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The one-carbon fragment of methylenetetrahydrofolate is reduced to a methyl group, releasing dihydrofolate.
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Dihydrofolate reductase reduces dihydrofolate back to tetrahydrofolate.
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Thymidylate synthase and dihydrofolate reductase are especially active in tissues with a high rate of cell division.

Therapeutic inhibitors

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Methotrexate is an analog of 10-methyltetrahydrofolate that inhibits dihydrofolate reductase and is used in cancer chemotherapy.
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Dihydrofolate reductases of some bacteria and parasites differ from the human enzyme, allowing their inhibitors to be used as antimicrobial drugs.
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Trimethoprim is an antibacterial example, and pyrimethamine is an antimalarial example.
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