Methotrexate (Amethopterin) (4-Amino-10-Methylfolate)

Methotrexate is an inhibitor of the enzyme dihydrofolate reductase and is used in the treatment of diseases. Inhibition of dihydrofolate reductase by methotrexate shuts down de novo biosynthesis of dTMP (Figure 22.18), because when the enzyme is inhibited, dihydrofolate (DHF) cannot be converted back to 5,10-Methylene THF, an essential intermediate in the de novo synthetic pathway.

See also: De Novo Biosynthesis of Purine Nucleotides, Tetrahydrofolate Coenzymes, Nucleotide Analogs in Medicine, Trimethoprim, Biosynthesis of Thymine Deoxyribonucleotides

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