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Pathway Description
Folate Biosynthesis
Escherichia coli
Metabolic Pathway
The biosynthesis of folic acid begins as a product of purine nucleotides de novo biosynthesis pathway. Purine nucleotides are involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphorylated through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter product reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. 7,8 -dihydroneopterin reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. Continuing, 6-hydroxymethyl-7,9-dihydropterin is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate.
Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter product is then catalyzed via an aminodeoxychorismate lyase resulting in pyruvic acid, hydrogen ion and p-aminobenzoic acid.
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react with the help of a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound then reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthease / dihydrofolate synthease resulting in a 7,8-dihydrofolate monoglutamate. 7,8-dihydrofolate monoglutamate is then reduced via a NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate which will continue and become a metabolite of the folate pathway
References
Folate Biosynthesis References
Appling DR: Compartmentation of folate-mediated one-carbon metabolism in eukaryotes. FASEB J. 1991 Sep;5(12):2645-51.
Pubmed: 1916088
Cossins EA, Chen L: Folates and one-carbon metabolism in plants and fungi. Phytochemistry. 1997 Jun;45(3):437-52.
Pubmed: 9190084
Feinleib M, Beresford SA, Bowman BA, Mills JL, Rader JI, Selhub J, Yetley EA: Folate fortification for the prevention of birth defects: case study. Am J Epidemiol. 2001 Dec 15;154(12 Suppl):S60-9.
Pubmed: 11744531
Hanson AD, Gregory JF 3rd: Synthesis and turnover of folates in plants. Curr Opin Plant Biol. 2002 Jun;5(3):244-9.
Pubmed: 11960743
HERBERT V, LARRABEE AR, BUCHANAN JM: Studies on the identification of a folate compound of human serum. J Clin Invest. 1962 May;41:1134-8. doi: 10.1172/JCI104565.
Pubmed: 13906633
Illarionova V, Eisenreich W, Fischer M, Haussmann C, Romisch W, Richter G, Bacher A: Biosynthesis of tetrahydrofolate. Stereochemistry of dihydroneopterin aldolase. J Biol Chem. 2002 Aug 9;277(32):28841-7. doi: 10.1074/jbc.M204046200. Epub 2002 May 30.
Pubmed: 12039964
Jabrin S, Ravanel S, Gambonnet B, Douce R, Rebeille F: One-carbon metabolism in plants. Regulation of tetrahydrofolate synthesis during germination and seedling development. Plant Physiol. 2003 Mar;131(3):1431-9. doi: 10.1104/pp.016915.
Pubmed: 12644692
Lucock M: Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab. 2000 Sep-Oct;71(1-2):121-38. doi: 10.1006/mgme.2000.3027.
Pubmed: 11001804
Lucock MD, Hartley R, Smithells RW: A rapid and specific HPLC-electrochemical method for the determination of endogenous 5-methyltetrahydrofolic acid in plasma using solid phase sample preparation with internal standardization. Biomed Chromatogr. 1989 Mar;3(2):58-63. doi: 10.1002/bmc.1130030204.
Pubmed: 2736319
Mitchell HK, Snell EE, Williams RJ: Journal of the American Chemical Society, Vol. 63, 1941: The concentration of "folic acid" by Herschel K. Mitchell, Esmond E. Snell, and Roger J. Williams. Nutr Rev. 1988 Sep;46(9):324-5.
Pubmed: 3067148
Ravanel S, Cherest H, Jabrin S, Grunwald D, Surdin-Kerjan Y, Douce R, Rebeille F: Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15360-5. doi: 10.1073/pnas.261585098.
Pubmed: 11752472
Thien KR, Blair JA, Leeming RJ, Cooke WT, Melikian V: Serum folates in man. J Clin Pathol. 1977 May;30(5):438-48.
Pubmed: 405403
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