Dihydrofolate reductase (DHFR) is an enzyme that is involved in the metabolism of folate, a vitamin that is important for the synthesis of nucleic acids (DNA and RNA) and other essential cellular processes. DHFR catalyzes the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF), which is a cofactor required for the synthesis of nucleotides.
DHFR is a highly conserved enzyme that is present in a wide range of organisms, including bacteria, plants, and animals. It is the target of several drugs, including methotrexate, which is commonly used as a chemotherapy agent for the treatment of cancer. Methotrexate works by inhibiting DHFR activity, which disrupts nucleotide synthesis and cell division.
In biotechnology, DHFR is also used as a selectable marker in the production of recombinant proteins, as cells that lack DHFR activity require exogenous folic acid and thymidine for survival. By introducing the gene for DHFR into cells that lack it, and selecting for cells that are resistant to methotrexate, stable cell lines can be generated that are capable of expressing and producing high levels of a recombinant protein of interest.
Overall, DHFR is an important enzyme with diverse roles in cellular metabolism and biotechnology, and its study has contributed significantly to our understanding of basic biochemistry and the development of new therapeutic agents.