Reaction 12 (Refer Figure 11.7) is the sole reaction of pyrimidine nucleotide biosynthesis, which requires a tetrahydrofolate derivative. During the transfer process, the methylene group of N⁵ and N¹⁰ methylene THF is reduced to a methyl group, and the tetra hydrofolate carrier oxidised to dihydrofolate must be reduced to tetrahydrofolate in a reaction catalysed by tetrahydrofolate reductase. Consequently, dividing the cells that are necessity-generating TMP and dihydrofolate are especially sensitive to inhibitors of dihydrofolate reductase. One such inhibitor is methotrexate (amethopterin), a widely used anti-cancer drug.