Question

does methotrexate inhibit folic acid synthesis or Thymidylate synthase?

Answer 1

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.