Dihyrofolate reductase

The reaction catalyzed by thymidylate synthase is the only one known in the cell in which tetrahydrofolate is not regenerated. Dihyrofolate reductase, thus, plays an essential role in the ultimate regeneration of 5,10-methylene tetrahydrofolate. This enzyme, which can be inhibited by the drug methotrexate, is a target of some anticancer treatments. 

Methotrexate and trimethoprim are both inhibitors of dihyrofolate reductase. Why is trimethoprim the drug of choice in treating a human microbial infection ... 

D. McElheny, J.R. Schell, J.C. Lansing, H.J. Dyson, P.E. Wright, Defining the role of active-site loop fluctuations in dihyrofolate reductase catalysis, Proc. Nad. Acad. Sci. U. S. A. 102 (2005) 5032-5037. 

Figure 6. Some common pharmaceuticals that inhibit enzymes. Methotrexate binds to the enzyme that normally uses dihyrofolate. This binding prevents the enzyme from binding dihydrofolate reductase and carrying out its function. Inhibition of these enzymes is toxic for virtually al I cells but has some selectivity for rapidly dividing cells. Warfarin binds to an enzyme site that is normally occupied by vitamin K. Again, with warfarin bound, liver enzymes that aid in synthesis of certain blood clotting proteins cannot function properly. As a resuitthe blood clotting proteins produced are defective and there is reduced ability to clot blood.

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