C-1-tetrahydrofolate synthase, cytoplasmic also known as C1-THF synthase is an enzyme that in humans is encoded by the MTHFD1 (methylenetetrahydrofolate dehydrogenase 1) gene.[1][2][3]
Function
This gene encodes a protein that possesses three distinct enzymatic activities, methylenetetrahydrofolate dehydrogenase (1.5.1.5), methenyltetrahydrofolate cyclohydrolase (3.5.4.9) and formate–tetrahydrofolate ligase (6.3.4.3). Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain.[3][4]
References
↑Hum DW, Bell AW, Rozen R, MacKenzie RE (Dec 1988). "Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase". J Biol Chem. 263 (31): 15946–50. PMID3053686.
↑Watkins D, Schwartzentruber JA, Ganesh J, Orange JS, Kaplan BS, Nunez LD, Majewski J, Rosenblatt DS (September 2011). "Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband". J. Med. Genet. 48 (9): 590–2. doi:10.1136/jmedgenet-2011-100286. PMID21813566.
MacKenzie RE, Mejia N, Yang XM (1989). "Methylenetetrahydrofolate dehydrogenases in normal and transformed mammalian cells". Adv. Enzyme Regul. 27: 31–9. doi:10.1016/0065-2571(88)90007-6. PMID3074630.
Shannon KW, Rabinowitz JC (1986). "Purification and characterization of a mitochondrial isozyme of C1-tetrahydrofolate synthase from Saccharomyces cerevisiae". J. Biol. Chem. 261 (26): 12266–71. PMID3528153.
Mejia NR, MacKenzie RE (1985). "NAD-dependent methylenetetrahydrofolate dehydrogenase is expressed by immortal cells". J. Biol. Chem. 260 (27): 14616–20. PMID3877056.
Allaire M, Li Y, MacKenzie RE, Cygler M (1998). "The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5 A resolution". Structure. 6 (2): 173–82. doi:10.1016/S0969-2126(98)00019-7. PMID9519408.
Hol FA, van der Put NM, Geurds MP, et al. (1998). "Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects". Clin. Genet. 53 (2): 119–25. doi:10.1111/j.1399-0004.1998.tb02658.x. PMID9611072.
Schmidt A, Wu H, MacKenzie RE, et al. (2000). "Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase". Biochemistry. 39 (21): 6325–35. doi:10.1021/bi992734y. PMID10828945.
Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID12665801.
Parle-McDermott A, Mills JL, Kirke PN, et al. (2005). "MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae". Am. J. Med. Genet. A. 132 (4): 365–8. doi:10.1002/ajmg.a.30354. PMID15633187.
Parle-McDermott A, Pangilinan F, Mills JL, et al. (2005). "A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss". Mol. Hum. Reprod. 11 (7): 477–80. doi:10.1093/molehr/gah204. PMID16123074.
De Marco P, Merello E, Calevo MG, et al. (2006). "Evaluation of a methylenetetrahydrofolate-dehydrogenase 1958G>A polymorphism for neural tube defect risk". J. Hum. Genet. 51 (2): 98–103. doi:10.1007/s10038-005-0329-6. PMID16315005.
Sun J, Xu Y, Zhu Y, Lu H (2007). "Methylenetetrahydrofolate reductase gene polymorphism, homocysteine and risk of macroangiopathy in Type 2 diabetes mellitus". J. Endocrinol. Invest. 29 (9): 814–20. doi:10.1007/bf03347376. PMID17114913.
