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How does methotrexate inhibit dNTP synthesis (be specific)? Why is possible to inhibit cancer cell growth...

How does methotrexate inhibit dNTP synthesis (be specific)? Why is possible to inhibit cancer cell growth by targeting this particular step in dNTP synthesis?

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Answer #1

The mechnism of action of methotrexate is that it inhibits DHFR (dihydrofolate reductase), an enzyme responsible for synthesis of tetrahydrofolate.

It inhibits the enzyme by competing with folate as it has many times affinity for enzyme as compared to folate. We know that Folic acid is required for sysnthesis of thymidine (a nucleoside)present in DNA.

Folate is required for biosynthesis of nitrogen bases (present in DNA and RNA). so synthesis of nitrogen bases inhibitied by action of methotrexate.

This can also be related to inhibit growth of cancer cells as methotrexate inhibit sysnthesis of nitrogen bases and hence affect sysnthesis of DNA, RNA protein etc.

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