Editing Dihydrofolate reductase (section)

== Function ==
{{Infobox enzyme
| Name       = Dihydrofolate reductase
| EC_number  = 1.5.1.3
| CAS_number = 9002-03-3
| GO_code    = 0004146
}}
Dihydrofolate reductase converts [[dihydrofolate]] into [[tetrahydrofolate]], a proton shuttle required for the de novo synthesis of [[purines]], [[thymidine monophosphate|thymidylic acid]], and certain [[amino acid]]s. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes.<ref name="entrez">{{cite web | title = Entrez Gene: DHFR dihydrofolate reductase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1719}}</ref>

<gallery class="skin-invert-image" mode=packed>
Image:DHFR rxn.svg|Reaction catalyzed by DHFR.
Image:THFsynthesispathway.png|Tetrahydrofolate synthesis pathway.
</gallery>

Found in all organisms, DHFR has a critical role in regulating the amount of tetrahydrofolate in the cell. Tetrahydrofolate and its derivatives are essential for [[purine]] and [[thymidylate]] synthesis, which are important for cell proliferation and cell growth.<ref name="pmid15139807">{{cite journal | vauthors = Schnell JR, Dyson HJ, Wright PE | s2cid = 28611812 | title = Structure, dynamics, and catalytic function of dihydrofolate reductase | journal = Annual Review of Biophysics and Biomolecular Structure | volume = 33 | issue = 1 | pages = 119–40 | year = 2004 | pmid = 15139807 | doi = 10.1146/annurev.biophys.33.110502.133613 }}</ref> DHFR plays a central role in the synthesis of [[nucleic acid]] precursors, and it has been shown that mutant cells that completely lack DHFR require glycine, a purine, and thymidine to grow.<ref name="pmid6933469">{{cite journal | vauthors = Urlaub G, Chasin LA | title = Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 7 | pages = 4216–20 | date = July 1980 | pmid = 6933469 | pmc = 349802 | doi = 10.1073/pnas.77.7.4216 | bibcode = 1980PNAS...77.4216U | doi-access = free }}</ref> DHFR has also been demonstrated as an enzyme involved in the salvage of [[tetrahydrobiopterin]] from [[dihydrobiopterin]].<ref>{{cite journal | vauthors = Crabtree MJ, Tatham AL, Hale AB, Alp NJ, Channon KM | title = Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways | journal = The Journal of Biological Chemistry | volume = 284 | issue = 41 | pages = 28128–36 | date = October 2009 | pmid = 19666465 | pmc = 2788863 | doi = 10.1074/jbc.M109.041483 | doi-access = free }}</ref><ref>{{cite book|year=1989|title=Folates and Cobalamins|chapter=Chapter 17: The Relationship Between Biopterin and Folate Metabolism|vauthors=Harpey JP|pages=215-218|veditors=Zittoun JA, Cooper BA|isbn=978-3-540-50653-9|doi=10.1007/978-3-642-74364-1_17|publisher=Springer-Verlag}}</ref>