Which of the following is a dihydrofolate reductase inhibitor: March 2009
**Core Concept**
Dihydrofolate reductase (DHFR) inhibitors are a class of medications that block the enzyme dihydrofolate reductase, which is crucial for the synthesis of tetrahydrofolate (THF) from dihydrofolate (DHF). THF is essential for DNA synthesis and repair, making DHFR inhibitors effective in treating various cancers and certain hematologic disorders.
**Why the Correct Answer is Right**
Methotrexate is a well-known DHFR inhibitor that works by competitively inhibiting the enzyme dihydrofolate reductase. This inhibition disrupts the conversion of dihydrofolate to tetrahydrofolate, which is necessary for the synthesis of thymidine monophosphate (TMP), an essential nucleotide for DNA replication. By depriving cancer cells of TMP, methotrexate exerts its anti-tumor effects.
**Why Each Wrong Option is Incorrect**
**Option A:** Folic acid is actually a precursor to dihydrofolate, which is then converted to tetrahydrofolate by the action of dihydrofolate reductase. As such, it is not a DHFR inhibitor.
**Option B:** Cyclophosphamide is an alkylating agent that interferes with DNA replication, but it does not inhibit dihydrofolate reductase.
**Option C:** Chloramphenicol is an antibiotic that inhibits protein synthesis, not dihydrofolate reductase.
**Clinical Pearl / High-Yield Fact**
DHFR inhibitors like methotrexate are contraindicated in pregnancy due to the risk of fetal harm, as they can inhibit the synthesis of tetrahydrofolate, which is essential for fetal development.
**Correct Answer:** A. Methotrexate