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Pathway Description
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-16
Methylenetetrahydrofolate reductase deficiency (MTHFRD; Homocystinuria due to defect of n(5,10)-methylene THF deficiency) is caused by a defect in the MTHFR gene which codes for methylenetetrahydrofolate reductase. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. A defect in this enzyme results in accumulation of homocysteine and methionine in both plasma and urine. Some of the symptoms and signs include mental retardation, withdrawal, hallucinations, delusions, muscle weakness. Some patients remain asymptomatic until adulthood.
References
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD) References
Fattal-Valevski A, Bassan H, Korman SH, Lerman-Sagie T, Gutman A, Harel S: Methylenetetrahydrofolate reductase deficiency: importance of early diagnosis. J Child Neurol. 2000 Aug;15(8):539-43. doi: 10.1177/088307380001500808.
Pubmed: 10961793
Dean L: Methylenetetrahydrofolate Reductase Deficiency
Pubmed: 28520345
Folate Metabolism References
Wang Y, Bruenn JA, Queener SF, Cody V: Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzyme. Antimicrob Agents Chemother. 2001 Sep;45(9):2517-23. doi: 10.1128/aac.45.9.2517-2523.2001.
Pubmed: 11502523
Hughes L, Carton R, Minguzzi S, McEntee G, Deinum EE, O'Connell MJ, Parle-McDermott A: An active second dihydrofolate reductase enzyme is not a feature of rat and mouse, but they do have activity in their mitochondria. FEBS Lett. 2015 Jul 8;589(15):1855-62. doi: 10.1016/j.febslet.2015.05.017. Epub 2015 May 14.
Pubmed: 25980602
Thigpen AE, West MG, Appling DR: Rat C1-tetrahydrofolate synthase. cDNA isolation, tissue-specific levels of the mRNA, and expression of the protein in yeast. J Biol Chem. 1990 May 15;265(14):7907-13.
Pubmed: 2186031
Cook RJ, Lloyd RS, Wagner C: Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 1991 Mar 15;266(8):4965-73.
Pubmed: 1848231
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Pubmed: 15489334
Krupenko SA, Wagner C: Aspartate 142 is involved in both hydrolase and dehydrogenase catalytic centers of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 1999 Dec 10;274(50):35777-84. doi: 10.1074/jbc.274.50.35777.
Pubmed: 10585460
Gao YS, Alvarez C, Nelson DS, Sztul E: Molecular cloning, characterization, and dynamics of rat formiminotransferase cyclodeaminase, a Golgi-associated 58-kDa protein. J Biol Chem. 1998 Dec 11;273(50):33825-34. doi: 10.1074/jbc.273.50.33825.
Pubmed: 9837973
Bashour AM, Bloom GS: 58K, a microtubule-binding Golgi protein, is a formiminotransferase cyclodeaminase. J Biol Chem. 1998 Jul 31;273(31):19612-7. doi: 10.1074/jbc.273.31.19612.
Pubmed: 9677387
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.
Pubmed: 15057822
Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.
Pubmed: 15632090
Yao R, Nimec Z, Ryan TJ, Galivan J: Identification, cloning, and sequencing of a cDNA coding for rat gamma-glutamyl hydrolase. J Biol Chem. 1996 Apr 12;271(15):8525-8. doi: 10.1074/jbc.271.15.8525.
Pubmed: 8621474
Wang Y, Nimec Z, Ryan TJ, Dias JA, Galivan J: The properties of the secreted gamma-glutamyl hydrolases from H35 hepatoma cells. Biochim Biophys Acta. 1993 Aug 7;1164(3):227-35. doi: 10.1016/0167-4838(93)90253-n.
Pubmed: 8343522
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000543
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