Tetrahydrofolate Dehydrogenase (Dihydrofolate Reductase)

An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.

Also Known As:

Networked: 598 relevant articles (13 outcomes, 46 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Queener, Sherry F: 9 articles (10/2011 - 01/2003)
2.	Yuthavong, Yongyuth: 7 articles (09/2011 - 01/2002)
3.	Rosowsky, Andre: 7 articles (03/2009 - 01/2002)
4.	Bertino, Joseph R: 6 articles (02/2013 - 06/2003)
5.	Gangjee, Aleem: 5 articles (09/2014 - 11/2003)
6.	Banerjee, Debabrata: 5 articles (02/2013 - 06/2003)
7.	Chitnumsub, Penchit: 5 articles (09/2011 - 03/2003)
8.	Kamchonwongpaisan, Sumalee: 5 articles (09/2011 - 06/2006)
9.	Choi, Seok Ki: 4 articles (01/2015 - 01/2012)
10.	Anderson, Amy C: 4 articles (06/2014 - 03/2007)

Related Diseases

1.	Neoplasms (Cancer) 07/01/2013 - "Dihydrofolate reductase (DHFR) has been used successfully as a drug target in the area of anti-bacterial, anti-cancer and anti-malarial therapy. " 01/01/2013 - "Although dihydrofolate reductase (DHFR) is a well-known target for the anti-tumor effect of MTX, the mode of action for the anti-inflammatory activity of MTX is not fully understood. " 12/01/2011 - "From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined. " 09/01/2010 - "Dihydrofolate reductase (DHFR) has been used successfully as a drug target in the area of anti-bacterial, anti-cancer and anti-malarial therapy. " 03/01/2010 - "Since MTX prevents tumor cells from proliferating by inhibiting dihydrofolate reductase (DHFR), DHFR expression is a key determinant of resistance to MTX in malignant hematological tumor cells. "
2.	Malaria 12/01/2001 - "Yeast can now be used to study antifolate drug resistance patterns that depend on the dihydrofolate reductase enzyme (DHFR) from the malaria parasite." 05/01/2013 - "Malaria treatment failure with novel mutation in the Plasmodium falciparum dihydrofolate reductase (pfdhfr) gene in Kolkata, West Bengal, India." 11/15/2011 - "Malaria antifolate resistance with contrasting Plasmodium falciparum dihydrofolate reductase (DHFR) polymorphisms in humans and Anopheles mosquitoes." 07/21/2009 - "The coding sequence for dihydrofolate reductase (DHFR) from the malaria parasite Plasmodium falciparum was mutagenized, and tests were carried out in Escherichia coli under conditions in which the endogenous bacterial enzyme was selectively inhibited. " 02/01/2008 - "The success of inhibitors of the enzyme dihydrofolate reductase (DHFR) against malaria has encouraged further exploration of this strategy against other parasites. "
3.	Infection 12/15/2002 - "Samples from 71 recurrent infections, collected over a 9-week follow-up, showed selection for parasites with the triple mutant Ile(51)-Arg(59)-Asn(108) in dihydrofolate reductase. " 07/01/1981 - "Following polyoma infection, an increase in the percentage of S-phase cells began at approximately 20 hours; dihydrofolate reductase synthesis also increased following a lag of 20 hours or more, and continued to increase throughout the late phase of lytic infection, reaching values nearly fivefold greater than that originally present in the quiescent cells. " 01/25/1979 - "The increase in dihydrofolate reductase synthesis begins 15 to 20 h after infection and continues to increase until cell lysis. " 06/01/1973 - "Various properties of the bacteriophage structural dihydrofolate reductase (DFR) have been examined to determine its function during phage infection. " 06/01/1973 - "Function of T4D structural dihydrofolate reductase in bacteriophage infection."
4.	Leukemia L1210 04/07/1972 - "Improved purification of tetrahydrofolate dehydrogenase from L1210 leukemia by affinity chromatography." 10/01/1991 - "Evidence for kinetic and immunologic heterogeneity of dihydrofolate reductase in L1210 leukemia cells." 03/01/1989 - "A 3-hr exposure of L1210 leukemia cells to 100 microM 7-OH-MTX produced negligible suppression of cell growth despite the build-up of intracellular polyglutamyl congeners to levels 2.7 times greater than the dihydrofolate reductase (DHFR) binding capacity. " 09/01/1986 - "All the gamma-monoamides were tested as inhibitors of purified dihydrofolate reductase (DHFR) from murine L1210 leukemia cells and as inhibitors of the growth of wild-type L1210 cells and a subline (L1210/R81) with high-level resistance to MTX and AMT based mainly on a defect in drug uptake via active transport. " 02/01/1985 - "Each of the compounds was a potent inhibitor of dihydrofolate reductase (DHFR) from rat liver or L1210 leukemia cells having I50 values in a range similar to that of 1a. "
5.	Osteosarcoma (Osteogenic Sarcoma) 01/01/1987 - "It is concluded that HDMTX-LV therapy may be effective in the treatment of osteosarcoma, even when subpopulations of the tumor cells exhibit different mechanisms of resistance to MTX, such as elevated levels of dihydrofolate reductase or a deficient transport system for MTX, if high doses of MTX are applied long enough to ensure lethal intracellular MTX levels and low-dose LV schedules instituted after a long delay are used." 08/01/2008 - "Aims of this study were the validation of C-MYC involvement in methotrexate (MTX) resistance and the assessment of clinical impact of C-MYC and dihydrofolate reductase (DHFR) in osteosarcoma (OS). " 08/01/2008 - "Clinical impact of the methotrexate resistance-associated genes C-MYC and dihydrofolate reductase (DHFR) in high-grade osteosarcoma." 06/01/2003 - "Previous studies have shown that decreased expression of the reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR) are associated with intrinsic and acquired methotrexate resistance, respectively, in osteosarcoma (OS). " 05/01/2009 - "Methotrexate in pediatric osteosarcoma: response and toxicity in relation to genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1 expression."

Related Drugs and Biologics

1.	Dihydropteroate Synthase (Dihydropteroate Synthetase)
2.	Methotrexate (Mexate)
3.	sulfadoxine-pyrimethamine (Fansidar)
4.	epiroprim
5.	Thymidylate Synthase
6.	Enzymes
7.	Trimetrexate (JB11)
8.	Fluorouracil (Carac)
9.	Thymidine Phosphorylase
10.	Trimethoprim (Proloprim)

Related Therapies and Procedures

1.	Adjuvant Chemotherapy
2.	Transplants (Transplant)
3.	Drug Therapy (Chemotherapy)
4.	Aftercare (After-Treatment)
5.	Therapeutics