In 1988 it was approved for Rheumatoid Arthritis. The effects of methotrexate are one of three modalities. The side effects of methotrexate are related to the interaction with the folic acid pathway. Dihydrofolate is converted to tetrahydrofolate, with dihydrofolate reductase enzyme. The main folic acid metabolite in the serum, is five methyl tetrahydrofolate.
Folates enter the cell and are converted into polyglutamated forms.
These are retained in the cell, and are involved in carbon transfer reactions. They have a role in purine metabolism. They are required in the formation of nucleic acid. Five methyl tetrahydrofolate is necessary in the formation of homocysteine from methionine. Methotrexate is structurally similar to dihydrofolate.