Creative Enzymes is the most experienced service provider specialized in enzyme activity assays, especially for dihydrofolate reductase, based on years of experiences in developing and optimizing the method. Our services are the most trusted and proven, receiving tens of thousands of request every year. With the marketing and technical support by Creative Enzymes, your business is positioned to succeed.

Dihydrofolate reductase (EC 1.5.1.3; 5,6,7,8-tetrahydrofolate:NADP⁺ oxidoreductase; DHFR) is a ubiquitous enzyme necessary for normal cellular metabolism not only in prokaryotic cells but also in eukaryotic cells. Dihydrofolate reductase catalyzes the reduction of 7,8-dihydrofolate (H₂F) to 5,6,7,8-tetrahydrofolate (H₄F), and the conversion of folate to 5,6,7,8-tetrahydrofolate (H₄F) at a much slower rate. The reaction is NADPH-dependent, although NADH will also work, although less efficiently.

The primary physiological role of dihydrofolate reductase is regulating the amount of the tetrahydrofolate in the cell, a precursor of cofactors required for the biosynthesis of purines, pyrimidines, and different amino acids. The most important transformation involving 5,6,7,8-tetrahydrofolate, correlating with dihydrofolate reductase related chemotherapy is the biosynthesis of thymidylate (dTMP). For balanced cell growth, continuous supply of 5,6,7,8-tetrahydrofolate is required, which is possible only by replenishing dihydrofolate reductase. Inhibition of dihydrofolate reductase results in a cellular decrease of 5,6,7,8-tetrahydrofolate cofactors and hence disrupts the synthesis of purines, pyrimidines and several amino acids. This process eventually causes cell death. So it can be concluded that dihydrofolate reductase is an attractive pharmaceutical target for inhibition due to its pivotal role in DNA precursor synthesis. Many antineoplastic and antimicrobial drugs, such as methotrexate (inhibiting mammalian dihydrofolate reductase), trimethoprim (inhibiting bacterial dihydrofolate reductase), and pyrimethamine act by inhibiting dihydrofolate reductase. Besides, the mutations of dihydrofolate reductase can cause a rare autosomal recessive inborn error of folate metabolism, resulting in megaloblastic anemia and pancytopenia. This enzyme can also be targeted in the treatment of cancer. Moreover, the clinical importance of dihydrofolate reductase has made it a long-range target for enzymological studies. For example, dihydrofolate reductase from Escherichia coli is a preferred model system for enzymological studies due to its monomeric structure with no metals, no S-S bonds and reversible folding ability.

Figure: The crystal structure of E. Coli dihydrofolate reductase complexed with folate and NADP⁺.
PDB: 4X5F

To conclude, dihydrofolate reductase plays a pivotal role in clinical, pharmaceutical and therapeutic applications. In order to get a thorough understanding of this enzyme, more detailed knowledge should be gained, especially through its catalytic activity quantification. Creative Enzymes is a leading company which has participated in the industry of enzyme activity measurement for many years. We possess superb technology, professional knowledge, and the most advanced equipment that can support your research in an excellent way. Our prompt service, good customer care and dedicated approaches have made Creative Enzymes the most preferred vendor in the global market.