Dihydrofolate reductase

Dihydrofolate reductase (DHFR) is an enzyme that plays a crucial role in the folic acid metabolic pathway. It is responsible for the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF), which is a necessary step in the synthesis of nucleotides and certain amino acids.

Function

DHFR catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate (THF) using NADPH as a cofactor. This reaction is critical in the folic acid pathway as it provides the THF necessary for the synthesis of purines, thymidylate, and certain amino acids. Without DHFR, cells would be unable to synthesize these essential molecules, leading to impaired DNA replication and cell division.

Clinical significance

Due to its crucial role in cell division, DHFR is a target for a number of chemotherapeutic drugs, including methotrexate and trimethoprim. These drugs inhibit the activity of DHFR, preventing the synthesis of new DNA and leading to cell death. This makes them effective in treating rapidly dividing cells, such as those found in cancer and certain bacterial infections.

However, the use of DHFR inhibitors can also lead to side effects due to the inhibition of normal cell division. These can include anemia, due to the inhibition of red blood cell production, and immunosuppression, due to the inhibition of white blood cell production.

See also

• Folic acid
• Methotrexate
• Trimethoprim
• Chemotherapy

References

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