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Pathway Description
Pterin Biosynthesis (Folate Precursor)
Arabidopsis thaliana
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2017-01-31
Last Updated: 2025-02-08
Pterin biosynthesis is a pathway located in the cytosol by which GTP becomes hydroxymethyldihydropterin (HMDHP), the pterin precursor of folate biosynthesis. Firstly, GTP cyclohydrolase (GCH) catalyzes the conversion of GTP and water to dihydroneopterin triphosphate, formic acid, and water. Secondly, nudix hydrolase from the Nudix (NUcleotide DIphosphates linked to some moiety X) protein family of phosphohydrolases uses water to eliminate a pyrophosphate from dihydroneopterin phosphate and releases a hydrogen ion in the process. However, this enzyme is non-specific for this reaction, and therefore the true dihydroneopterin triphosphate diphosphatase may yet to be found. Thirdly, dihydroneopterin phosphate phosphatase (Pase) dephosphorylates dihydroneopterin phosphate to 7,8-dihydroneopterin. This enzyme has not yet been identified in any organism, but it is possible that reaction is carried out by a nonspecific phosphatase. The fourth reaction is catalyzed by the enzyme dihydroneopterin aldolase (DHNA) whereby 7,8-dihydroneopterin is cleaved to form HMDHP and glycolaldehyde is released. The second function of DHNA is epimerizing 7,8-dihydroneopterin to form 7,8-dihydromonapterin. DHNA can also use 7,8-dihydromonapterin as a substrate to form HMDHP. HMDHP has two fates. It can either be pumped into the mitochondria by a yet to be discovered HMDHP transporter for use in folate biosynthesis, or be acted upon by cytosolic hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase (HPPK-DHPS). HPPK-DHPS is a bifunctional enzyme that requires magnesium as a cofactor and catalyzes consecutive steps in the pterin and folate biosynthesis pathways. 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.
References
Pterin Biosynthesis (Folate Precursor) References
Hanson AD, Gregory JF 3rd: Folate biosynthesis, turnover, and transport in plants. Annu Rev Plant Biol. 2011;62:105-25. doi: 10.1146/annurev-arplant-042110-103819.
Pubmed: 21275646
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Pubmed: 22915736
Goyer A, Illarionova V, Roje S, Fischer M, Bacher A, Hanson AD: Folate biosynthesis in higher plants. cDNA cloning, heterologous expression, and characterization of dihydroneopterin aldolases. Plant Physiol. 2004 May;135(1):103-11. doi: 10.1104/pp.103.038430. Epub 2004 Apr 23.
Pubmed: 15107504
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Pubmed: 11130712
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
Seki M, Narusaka M, Kamiya A, Ishida J, Satou M, Sakurai T, Nakajima M, Enju A, Akiyama K, Oono Y, Muramatsu M, Hayashizaki Y, Kawai J, Carninci P, Itoh M, Ishii Y, Arakawa T, Shibata K, Shinagawa A, Shinozaki K: Functional annotation of a full-length Arabidopsis cDNA collection. Science. 2002 Apr 5;296(5565):141-5. doi: 10.1126/science.1071006. Epub 2002 Mar 21.
Pubmed: 11910074
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
Salanoubat M, Lemcke K, Rieger M, Ansorge W, Unseld M, Fartmann B, Valle G, Blocker H, Perez-Alonso M, Obermaier B, Delseny M, Boutry M, Grivell LA, Mache R, Puigdomenech P, De Simone V, Choisne N, Artiguenave F, Robert C, Brottier P, Wincker P, Cattolico L, Weissenbach J, Saurin W, Quetier F, Schafer M, Muller-Auer S, Gabel C, Fuchs M, Benes V, Wurmbach E, Drzonek H, Erfle H, Jordan N, Bangert S, Wiedelmann R, Kranz H, Voss H, Holland R, Brandt P, Nyakatura G, Vezzi A, D'Angelo M, Pallavicini A, Toppo S, Simionati B, Conrad A, Hornischer K, Kauer G, Lohnert TH, Nordsiek G, Reichelt J, Scharfe M, Schon O, Bargues M, Terol J, Climent J, Navarro P, Collado C, Perez-Perez A, Ottenwalder B, Duchemin D, Cooke R, Laudie M, Berger-Llauro C, Purnelle B, Masuy D, de Haan M, Maarse AC, Alcaraz JP, Cottet A, Casacuberta E, Monfort A, Argiriou A, flores M, Liguori R, Vitale D, Mannhaupt G, Haase D, Schoof H, Rudd S, Zaccaria P, Mewes HW, Mayer KF, Kaul S, Town CD, Koo HL, Tallon LJ, Jenkins J, Rooney T, Rizzo M, Walts A, Utterback T, Fujii CY, Shea TP, Creasy TH, Haas B, Maiti R, Wu D, Peterson J, Van Aken S, Pai G, Militscher J, Sellers P, Gill JE, Feldblyum TV, Preuss D, Lin X, Nierman WC, Salzberg SL, White O, Venter JC, Fraser CM, Kaneko T, Nakamura Y, Sato S, Kato T, Asamizu E, Sasamoto S, Kimura T, Idesawa K, Kawashima K, Kishida Y, Kiyokawa C, Kohara M, Matsumoto M, Matsuno A, Muraki A, Nakayama S, Nakazaki N, Shinpo S, Takeuchi C, Wada T, Watanabe A, Yamada M, Yasuda M, Tabata S: Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana. Nature. 2000 Dec 14;408(6814):820-2. doi: 10.1038/35048706.
Pubmed: 11130713
Bauer S, Schott AK, Illarionova V, Bacher A, Huber R, Fischer M: Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel adolase class. J Mol Biol. 2004 Jun 11;339(4):967-79. doi: 10.1016/j.jmb.2004.04.034.
Pubmed: 15165863
Basset G, Quinlivan EP, Ziemak MJ, Diaz De La Garza R, Fischer M, Schiffmann S, Bacher A, Gregory JF 3rd, Hanson AD: Folate synthesis in plants: the first step of the pterin branch is mediated by a unique bimodular GTP cyclohydrolase I. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12489-94. doi: 10.1073/pnas.192278499. Epub 2002 Sep 9.
Pubmed: 12221287
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