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Pathway Description
Folate Biosynthesis
Arabidopsis thaliana
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2017-02-01
Last Updated: 2025-12-05
Folate biosynthesis is a pathway by which pterin and pABA precursors form tetrahydrofolate, an essential cofactor that takes part in various enzymatic reactions as a carrier for one-carbon units. Although tetrahydrofolate is synthesized in the mitochondrial matrix, the pterin and pABA branches occur in the cytosol and the chloroplast, respectively. The first reaction in the pABA branch is catalyzed by aminodeoxychorismate synthase (ADCS) whereby chorismate and L-glutamine is converted to aminodeoxychorismate and L-glutamic acid. The second reaction in the pABA branch is catalyzed by aminodeoxychorismate lyase (ADCL) whereby aminodeoxychorismate is converted to pABA, pyruvic acid, and a hydrogen ion. pABA then diffuses out of the chloroplast and into the mitochondrial matrix to be used in folate biosynthesis. From the pterin branch, hydroxymethyldihydropterin (HMDHP) is pumped into the mitochondria by a yet to be discovered HMDHP transporter. The bifunctional enzyme hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase (HPPK-DHPS), which requires magnesium as a cofactor, catalyzes consecutive steps that unites the pABA and pterin branches. The HPPK domain uses ATP to diphosphorylate HMDHP to HMDHP pyrophosphate, releasing AMP and a hydrogen ion in the process. The DHPS domain incorporates pABA, diffused out from the chloroplast, to form dihydropteroate and a diphosphate. Next, dihydrofolate (DHF) synthase catalyzes the ATP hydrolysis powered conversion of dihydropteroate and L-glutamic acid to dihydrofolate. Finally, the DHFR domain of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) reduces dihydrofolate to tetrahydrofolate with the help of NADPH and a hydrogen ion.
References
Folate Biosynthesis References
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Pubmed: 21275646
Gerdes S, Lerma-Ortiz C, Frelin O, Seaver SM, Henry CS, de Crecy-Lagard V, Hanson AD: Plant B vitamin pathways and their compartmentation: a guide for the perplexed. J Exp Bot. 2012 Sep;63(15):5379-95. doi: 10.1093/jxb/ers208. Epub 2012 Aug 21.
Pubmed: 22915736
Lazar G, Zhang H, Goodman HM: The origin of the bifunctional dihydrofolate reductase-thymidylate synthase isogenes of Arabidopsis thaliana. Plant J. 1993 May;3(5):657-68.
Pubmed: 8374616
Sahr T, Ravanel S, Basset G, Nichols BP, Hanson AD, Rebeille F: Folate synthesis in plants: purification, kinetic properties, and inhibition of aminodeoxychorismate synthase. Biochem J. 2006 May 15;396(1):157-62. doi: 10.1042/BJ20051851.
Pubmed: 16466344
Camara D, Richefeu-Contesto C, Gambonnet B, Dumas R, Rebeille F: The synthesis of pABA: Coupling between the glutamine amidotransferase and aminodeoxychorismate synthase domains of the bifunctional aminodeoxychorismate synthase from Arabidopsis thaliana. Arch Biochem Biophys. 2011 Jan 1;505(1):83-90. doi: 10.1016/j.abb.2010.09.010. Epub 2010 Sep 17.
Pubmed: 20851095
Basset GJ, Quinlivan EP, Ravanel S, Rebeille F, Nichols BP, Shinozaki K, Seki M, Adams-Phillips LC, Giovannoni JJ, Gregory JF 3rd, Hanson AD: Folate synthesis in plants: the p-aminobenzoate branch is initiated by a bifunctional PabA-PabB protein that is targeted to plastids. Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1496-501. doi: 10.1073/pnas.0308331100. Epub 2004 Jan 26.
Pubmed: 14745019
Kotani H, Nakamura Y, Sato S, Asamizu E, Kaneko T, Miyajima N, Tabata S: Structural analysis of Arabidopsis thaliana chromosome 5. VI. Sequence features of the regions of 1,367,185 bp covered by 19 physically assigned P1 and TAC clones. DNA Res. 1998 Jun 30;5(3):203-16. doi: 10.1093/dnares/5.3.203.
Pubmed: 9734815
Cheng CY, Krishnakumar V, Chan AP, Thibaud-Nissen F, Schobel S, Town CD: Araport11: a complete reannotation of the Arabidopsis thaliana reference genome. Plant J. 2017 Feb;89(4):789-804. doi: 10.1111/tpj.13415. Epub 2017 Feb 10.
Pubmed: 27862469
Yamada K, Lim J, Dale JM, Chen H, Shinn P, Palm CJ, Southwick AM, Wu HC, Kim C, Nguyen M, Pham P, Cheuk R, Karlin-Newmann G, Liu SX, Lam B, Sakano H, Wu T, Yu G, Miranda M, Quach HL, Tripp M, Chang CH, Lee JM, Toriumi M, Chan MM, Tang CC, Onodera CS, Deng JM, Akiyama K, Ansari Y, Arakawa T, Banh J, Banno F, Bowser L, Brooks S, Carninci P, Chao Q, Choy N, Enju A, Goldsmith AD, Gurjal M, Hansen NF, Hayashizaki Y, Johnson-Hopson C, Hsuan VW, Iida K, Karnes M, Khan S, Koesema E, Ishida J, Jiang PX, Jones T, Kawai J, Kamiya A, Meyers C, Nakajima M, Narusaka M, Seki M, Sakurai T, Satou M, Tamse R, Vaysberg M, Wallender EK, Wong C, Yamamura Y, Yuan S, Shinozaki K, Davis RW, Theologis A, Ecker JR: Empirical analysis of transcriptional activity in the Arabidopsis genome. Science. 2003 Oct 31;302(5646):842-6. doi: 10.1126/science.1088305.
Pubmed: 14593172
Storozhenko S, Navarrete O, Ravanel S, De Brouwer V, Chaerle P, Zhang GF, Bastien O, Lambert W, Rebeille F, Van Der Straeten D: Cytosolic hydroxymethyldihydropterin pyrophosphokinase/dihydropteroate synthase from Arabidopsis thaliana: a specific role in early development and stress response. J Biol Chem. 2007 Apr 6;282(14):10749-61. doi: 10.1074/jbc.M701158200. Epub 2007 Feb 8.
Pubmed: 17289662
Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R, Bowman CL, Brooks SY, Buehler E, Chan A, Chao Q, Chen H, Cheuk RF, Chin CW, Chung MK, Conn L, Conway AB, Conway AR, Creasy TH, Dewar K, Dunn P, Etgu P, Feldblyum TV, Feng J, Fong B, Fujii CY, Gill JE, Goldsmith AD, Haas B, Hansen NF, Hughes B, Huizar L, Hunter JL, Jenkins J, Johnson-Hopson C, Khan S, Khaykin E, Kim CJ, Koo HL, Kremenetskaia I, Kurtz DB, Kwan A, Lam B, Langin-Hooper S, Lee A, Lee JM, Lenz CA, Li JH, Li Y, Lin X, Liu SX, Liu ZA, Luros JS, Maiti R, Marziali A, Militscher J, Miranda M, Nguyen M, Nierman WC, Osborne BI, Pai G, Peterson J, Pham PK, Rizzo M, Rooney T, Rowley D, Sakano H, Salzberg SL, Schwartz JR, Shinn P, Southwick AM, Sun H, Tallon LJ, Tambunga G, Toriumi MJ, Town CD, Utterback T, Van Aken S, Vaysberg M, Vysotskaia VS, Walker M, Wu D, Yu G, Fraser CM, Venter JC, Davis RW: Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana. Nature. 2000 Dec 14;408(6814):816-20. doi: 10.1038/35048500.
Pubmed: 11130712
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
Kotani H, Nakamura Y, Sato S, Kaneko T, Asamizu E, Miyajima N, Tabata S: Structural analysis of Arabidopsis thaliana chromosome 5. II. Sequence features of the regions of 1,044,062 bp covered by thirteen physically assigned P1 clones. DNA Res. 1997 Aug 31;4(4):291-300. doi: 10.1093/dnares/4.4.291.
Pubmed: 9405937
Lin X, Kaul S, Rounsley S, Shea TP, Benito MI, Town CD, Fujii CY, Mason T, Bowman CL, Barnstead M, Feldblyum TV, Buell CR, Ketchum KA, Lee J, Ronning CM, Koo HL, Moffat KS, Cronin LA, Shen M, Pai G, Van Aken S, Umayam L, Tallon LJ, Gill JE, Adams MD, Carrera AJ, Creasy TH, Goodman HM, Somerville CR, Copenhaver GP, Preuss D, Nierman WC, White O, Eisen JA, Salzberg SL, Fraser CM, Venter JC: Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana. Nature. 1999 Dec 16;402(6763):761-8. doi: 10.1038/45471.
Pubmed: 10617197
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