How do antifolate drugs like methotrexate work?

Antifolate drugs, such as methotrexate, exert their effects primarily by inhibiting the enzyme dihydrofolate reductase (DHFR). This enzyme is crucial for converting dihydrofolate into tetrahydrofolate, which is an essential cofactor in the synthesis of nucleotides required for DNA and RNA production. By blocking this pathway, methotrexate effectively reduces the availability of nucleotides, thereby impairing DNA replication and cell division. This is particularly beneficial in the treatment of rapidly dividing cells, such as those found in certain cancers and autoimmune diseases.

The other options relate to processes that are not directly affected by methotrexate. For instance, promoting nucleic acid synthesis would be counterproductive to the action of methotrexate, as its primary role is to inhibit this process. Similarly, enhancing folate absorption does not align with the mechanism of antifolate drugs, which typically inhibit the utilization of folate rather than enhancing its uptake. The inhibition of RNA polymerases is also outside the direct action of methotrexate, as its mechanism specifically targets the folate metabolism pathway rather than directly acting on RNA synthesis machinery.