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What is Methotrexate blocks the synthesis of thymidine monophosphate by inhibiting the activity of the enzyme: and explain in detail?
Ans. A. Dihydrofolate reductasea. Synthesis of nucleic acids take place by de-nove and salvage pathway. In pyrimidine synthesis thymidine monophosphate is synthesized from uridine monophosphate by thymidylate synthase.b. Methylation occurs by N5-N10 tetrahydrofolate which is converted to dihydrofolate.c. Dihydrofolate reductase is required to regenerate tetrahydrofolate (THF).d. Thymidylate synthase and dihydrofolate reductase are target enzymes in cancer chemotherapy. Methotrexate and Aminopterin inhibit the activity of the enzyme DHF reductase.