Question

Explain why methotrexate inhibits the synthesis of histidine and methionine.

Short answer

Methotrexate works by preventing the regeneration of a cofactor called THF, which is required for the synthesis of histidine and methionine.

Step-by-step solution

Amino acids

Amino acids are the molecules that are used for the formation of the polypeptide chains that creates proteins after processing.Examples of amino acids include methionine, glycine, valine, histidine, phenylalanine, and so on.

Methotrexate inhibits the synthesis of histidine and methionine

Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme required for the synthesis of tetrahydrofolate (THF), in a competitive manner. As a result, the presence of methotrexate inhibits THF production.

The synthesis of histidine and methionine is linked to the thymidylate synthase thatcatalyze the oxidation of THF to DHF. As a result, THF deficiency inhibits the synthesis of both molecules.