Dihydrofolate reductase

• OMIM: 126060
• UniProt: P00374

Dihydrofolate reductase ( DHFR), and dihydrofolate reductase, are called enzymes that folic acid to dihydrofolic acid ( DHF) and DHF to tetrahydrofolic acid hydrate (THF). These reactions enable the vitamin folic acid and are indispensable for nucleotide biosynthesis in all living things. In humans, DHFR is present in all tissue types. Mutations at the DHFR gene can cause DHFR deficiency and megaloblastic anemia this.

DHFR in protozoa and some plants is a double enzyme which additionally has the function of the thymidylate synthase; due to this structural peculiarity is the protozoan DHFR target in the development of antibiotics, such as against the malaria parasite Plasmodium falciparum and Cryptosporidium.

Catalyzed reactions

7,8- dihydrofolic is with NADPH as electron donor to tetrahydrofolic acid reduced (see figure). Folic acid also can be reduced to DHF; However, this reaction proceeds more slowly.

Other Features

DHFR in the presence of endothelial cells is crucial for the function of tetrahydrobiopterin in NO synthase.

Regulation and inhibition

DHFR is an extensively studied enzyme that is considered as a target for chemotherapy, and in other diseases. The enzyme can be competitively inhibited by folic acid antagonists such as methotrexate, aminopterin or trimethoprim. The inhibition results in a lack of tetrahydrofolic acid, whereby the synthesis of thymine ( thymidylate synthase requires THF ) and purine synthesis (Structure of Puringrundkörpers ) is prevented, after which the cell dies.