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In: Biology

does methotrexate inhibit folic acid synthesis or Thymidylate synthase?

does methotrexate inhibit folic acid synthesis or Thymidylate synthase?

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Expert Solution

Answer-

According to the given question-

  • Methotrexate is work as antagonist of folate .Methotrexate responsible for  inhibiting the enzyme DHFR or dihydrofolate reductase catalyzes the reduction of folic acid into tetrahydrofolic acid.
  • This Tetrahydrofolate is regenerated by dihydrofolate reductase required for purine as well as thymidylate nucleotide biosynthesis.
  • methotrexate inhibit the activity of dihydrofolate reductase and this causes thymidylate and purines deficiency results in decrease rate of synthesis of  nucleic acid . so we can say that methotrexate play an important role in several process such as cellular replication, DNA synthesis, and DNA repair.
  • So methotrexate causes -
    • dihydrofolate reductase inhibition
    • thymidylate synthase inhibition
    • and reduced folate transportation.
  • methotrexate have high affinity for binding with  dihydrofolate reductase compared to folic acid .
  • Thymidylate synthetase enzyme convert uridine 5′-phosphate into thymidine 5′-phosphate. Cofactor methylenete trahydrofolate work as donor for formaldehyde and oxidized to dihydrofolate as well as reduced to tetrahydrofolate by dihydrofolate reductase enzyme.


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