Methotrexate

Abstract

Methotrexate, a close structural analog of folic acid (Fig. 1), is a cell-cycle-specific, cytotoxic (cytostatic), antimetabolitic, antiproliferative agent. It acts primarily to prevent cell division during that phase of the cell cycle in which DNA synthesis is maximal (the S phase) by competitively inhibiting the enzyme dihydrofolate reductase (DHFR). DHFR catalyzes the reduction of folic acid and of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF) (Fig. 1). The resultant unavailability of THF, when DHFR is inhibited, leads to cessation of the synthesis of thymidylic acid, inosinic acid, other purine metabolites, and the amino acids methionine and glycine (Letendre et al., 1985; Lampe, 1986). Inosinic acid is the precursor of purines needed for DNA and RNA syntheses, and thymidylic acid is a nucleotide that is specific to the DNA molecule (Miller et al., 1986). Methionine and glycine are important in protein synthesis.KeywordsRheumatoid ArthritisFolic AcidAcute LeukemiaPsoriatic ArthritisFolinic AcidThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.