Antimetabolites exert their effects primarily by substituting for normal metabolites in cellular biochemical reactions. For example, methotrexate is a common antimetabolite that inhibits the enzyme dihydrofolate reductase, essential for DNA synthesis. By blocking this enzyme, methotrexate prevents the formation of tetrahydrofolate, a folate derivative necessary for the synthesis of thymidine, leading to the inhibition of cell division.