If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: N10-formyl-THF biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Folate Biosynthesis|
Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655
Folates are tripartite molecules comprising pterin, p-aminobenzoate (pABA), and glutamate moieties. In natural folates the pterin ring exists in the dihydro or tetrahydro state. Folate usually has a gamma-linked polyglutamyl tail of up to eight residues attached to the first glutamate. The one-carbon units (methyl or formyl) are either attached to the N-5 of the pterin moiety, to the N-10 of the pABA moiety or bridged in between these two (e.g., 5,10-methenyl or methylene-THF). 10-formyl-tetrahydrofolates are involved in tetrahydrofolate, purine and formate synthesis [Nagy95, deCrecyLagard07].
About This Pathway
The formation of the formyl and methyl derivatives of tetrahydrofolate (vitamin B9) directly involved in or representing sidesteps of the biosynthesis of this vital cofactor is displayed in this pathway. Conversion of 10-formyl-tetrahydrofolate to tetrahydrofolate occurs either directly through hydrolysis or via 5-methyl-tetrahydrofolate in several steps [Nagy95, deCrecyLagard07].
Variants: 4-aminobenzoate biosynthesis , folate polyglutamylation , folate transformations I , folate transformations II , glutamate removal from folates , superpathway of tetrahydrofolate biosynthesis , superpathway of tetrahydrofolate biosynthesis and salvage , tetrahydrofolate biosynthesis , tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate
Unification Links: EcoCyc:1CMET2-PWY
deCrecyLagard07: de Crecy-Lagard V, El Yacoubi B, de la Garza RD, Noiriel A, Hanson AD (2007). "Comparative genomics of bacterial and plant folate synthesis and salvage: predictions and validations." BMC Genomics 8;245. PMID: 17645794
Nagy95: Nagy PL, Marolewski A, Benkovic SJ, Zalkin H (1995). "Formyltetrahydrofolate hydrolase, a regulatory enzyme that functions to balance pools of tetrahydrofolate and one-carbon tetrahydrofolate adducts in Escherichia coli." J Bacteriol 1995;177(5);1292-8. PMID: 7868604
Agrawal04: Agrawal N, Hong B, Mihai C, Kohen A (2004). "Vibrationally enhanced hydrogen tunneling in the Escherichia coli thymidylate synthase catalyzed reaction." Biochemistry 43(7);1998-2006. PMID: 14967040
Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554
Anderson11: Anderson DD, Quintero CM, Stover PJ (2011). "Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria." Proc Natl Acad Sci U S A 108(37);15163-8. PMID: 21876188
Appleman90: Appleman JR, Howell EE, Kraut J, Blakley RL (1990). "Role of aspartate 27 of dihydrofolate reductase from Escherichia coli in interconversion of active and inactive enzyme conformers and binding of NADPH." J Biol Chem 1990;265(10);5579-84. PMID: 2108144
Arai05: Arai M, Iwakura M (2005). "Probing the interactions between the folding elements early in the folding of Escherichia coli dihydrofolate reductase by systematic sequence perturbation analysis." J Mol Biol 347(2);337-53. PMID: 15740745
Arai07: Arai M, Kondrashkina E, Kayatekin C, Matthews CR, Iwakura M, Bilsel O (2007). "Microsecond Hydrophobic Collapse in the Folding of Escherichia coli Dihydrofolate Reductase, an alpha/beta-Type Protein." J Mol Biol 368(1);219-29. PMID: 17331539
Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699
Baccanari82: Baccanari DP, Daluge S, King RW (1982). "Inhibition of dihydrofolate reductase: effect of reduced nicotinamide adenine dinucleotide phosphate on the selectivity and affinity of diaminobenzylpyrimidines." Biochemistry 1982;21(20);5068-75. PMID: 6814484
Banerjee89: Banerjee RV, Johnston NL, Sobeski JK, Datta P, Matthews RG (1989). "Cloning and sequence analysis of the Escherichia coli metH gene encoding cobalamin-dependent methionine synthase and isolation of a tryptic fragment containing the cobalamin-binding domain." J Biol Chem 1989;264(23);13888-95. PMID: 2668277
Banerjee90: Banerjee RV, Frasca V, Ballou DP, Matthews RG (1990). "Participation of cob(I) alamin in the reaction catalyzed by methionine synthase from Escherichia coli: a steady-state and rapid reaction kinetic analysis." Biochemistry 1990;29(50);11101-9. PMID: 2271698
Batruch10: Batruch I, Javasky E, Brown ED, Organ MG, Johnson PE (2010). "Thermodynamic and NMR analysis of inhibitor binding to dihydrofolate reductase." Bioorg Med Chem 18(24);8485-92. PMID: 21084197
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