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Pathway Description
Ascorbate Metabolism
Arabidopsis thaliana
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2017-05-15
Last Updated: 2025-01-25
Vitamin C (ascorbate) is a vitamin found in food and used as a dietary supplement. The vast majority of animals and plants are able to synthesize vitamin C, through a sequence of enzyme-driven steps, which convert monosaccharides to vitamin C. In plants, this is accomplished through the conversion of mannose or galactose to ascorbic acid starting in the cytosol and ending in the mitochondrial matrix . First, GDP-mannose 3,5-epimerase catalyzes the reversible epimerization of GDP-D-mannose into either GDP-L-gulose or GDP-L-galactose. It also can reversibly epimerize GDP-L-gulose into GDP-L-galactose and vice versa. It requires NAD as a cofactor. Second, GDP-L-galactose phosphorylase catalyzes the conversion of GDP-L-galactose into L-galactose 1-phosphate. Third, L-galactose 1-phosphate phosphatase catalyzes the conversion of L-galactose 1-phosphate into L-galactose. It requires magnesium ion as a cofactor. Fourth, L-galactose dehydrogenase catalyzes the conversion of L-galactose into L-galactono-1,4-lactone. L-galactono-1,4-lactone must then be imported into the mitochondrial matrix by a predicted innermitochondrial membrane transporter to complete ascorbate synthesis. L-galactono-1,4-lactone dehydrogenase, localized to the innermitochondrial membrane (coloured dark green in the image), catalyzes two reactions in ascorbate metabolism: the conversion of L-galactono-1,4-lactone into L-ascorbate and the subsequent conversion of L-ascorbate into L-dehydroascorbate. It requires FAD as a cofactor. Ascorbate can then be converted into monodehydroascorbate radical by the mitochondrial L-ascorbate peroxidase S (this plays a key role in hydrogen peroxide removal). Monodehydroascorbate reductase 5 then can convert monodehydroascorbate radical back into L-ascorbate.
References
Ascorbate Metabolism References
Wolucka BA, Van Montagu M: GDP-mannose 3',5'-epimerase forms GDP-L-gulose, a putative intermediate for the de novo biosynthesis of vitamin C in plants. J Biol Chem. 2003 Nov 28;278(48):47483-90. doi: 10.1074/jbc.M309135200. Epub 2003 Sep 3.
Pubmed: 12954627
Linster CL, Adler LN, Webb K, Christensen KC, Brenner C, Clarke SG: A second GDP-L-galactose phosphorylase in arabidopsis en route to vitamin C. Covalent intermediate and substrate requirements for the conserved reaction. J Biol Chem. 2008 Jul 4;283(27):18483-92. doi: 10.1074/jbc.M802594200. Epub 2008 May 7.
Pubmed: 18463094
Leferink NG, van den Berg WA, van Berkel WJ: l-Galactono-gamma-lactone dehydrogenase from Arabidopsis thaliana, a flavoprotein involved in vitamin C biosynthesis. FEBS J. 2008 Feb;275(4):713-26. doi: 10.1111/j.1742-4658.2007.06233.x. Epub 2008 Jan 10.
Pubmed: 18190525
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Pubmed: 11130714
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
Linster CL, Gomez TA, Christensen KC, Adler LN, Young BD, Brenner C, Clarke SG: Arabidopsis VTC2 encodes a GDP-L-galactose phosphorylase, the last unknown enzyme in the Smirnoff-Wheeler pathway to ascorbic acid in plants. J Biol Chem. 2007 Jun 29;282(26):18879-85. doi: 10.1074/jbc.M702094200. Epub 2007 Apr 26.
Pubmed: 17462988
Muller-Moule P: An expression analysis of the ascorbate biosynthesis enzyme VTC2. Plant Mol Biol. 2008 Sep;68(1-2):31-41. doi: 10.1007/s11103-008-9350-4. Epub 2008 May 31.
Pubmed: 18516687
Jander G, Norris SR, Rounsley SD, Bush DF, Levin IM, Last RL: Arabidopsis map-based cloning in the post-genome era. Plant Physiol. 2002 Jun;129(2):440-50. doi: 10.1104/pp.003533.
Pubmed: 12068090
Conklin PL, Gatzek S, Wheeler GL, Dowdle J, Raymond MJ, Rolinski S, Isupov M, Littlechild JA, Smirnoff N: Arabidopsis thaliana VTC4 encodes L-galactose-1-P phosphatase, a plant ascorbic acid biosynthetic enzyme. J Biol Chem. 2006 Jun 9;281(23):15662-70. doi: 10.1074/jbc.M601409200. Epub 2006 Apr 4.
Pubmed: 16595667
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
Gatzek S, Wheeler GL, Smirnoff N: Antisense suppression of l-galactose dehydrogenase in Arabidopsis thaliana provides evidence for its role in ascorbate synthesis and reveals light modulated l-galactose synthesis. Plant J. 2002 Jun;30(5):541-53.
Pubmed: 12047629
Mayer K, Schuller C, Wambutt R, Murphy G, Volckaert G, Pohl T, Dusterhoft A, Stiekema W, Entian KD, Terryn N, Harris B, Ansorge W, Brandt P, Grivell L, Rieger M, Weichselgartner M, de Simone V, Obermaier B, Mache R, Muller M, Kreis M, Delseny M, Puigdomenech P, Watson M, Schmidtheini T, Reichert B, Portatelle D, Perez-Alonso M, Boutry M, Bancroft I, Vos P, Hoheisel J, Zimmermann W, Wedler H, Ridley P, Langham SA, McCullagh B, Bilham L, Robben J, Van der Schueren J, Grymonprez B, Chuang YJ, Vandenbussche F, Braeken M, Weltjens I, Voet M, Bastiaens I, Aert R, Defoor E, Weitzenegger T, Bothe G, Ramsperger U, Hilbert H, Braun M, Holzer E, Brandt A, Peters S, van Staveren M, Dirske W, Mooijman P, Klein Lankhorst R, Rose M, Hauf J, Kotter P, Berneiser S, Hempel S, Feldpausch M, Lamberth S, Van den Daele H, De Keyser A, Buysshaert C, Gielen J, Villarroel R, De Clercq R, Van Montagu M, Rogers J, Cronin A, Quail M, Bray-Allen S, Clark L, Doggett J, Hall S, Kay M, Lennard N, McLay K, Mayes R, Pettett A, Rajandream MA, Lyne M, Benes V, Rechmann S, Borkova D, Blocker H, Scharfe M, Grimm M, Lohnert TH, Dose S, de Haan M, Maarse A, Schafer M, Muller-Auer S, Gabel C, Fuchs M, Fartmann B, Granderath K, Dauner D, Herzl A, Neumann S, Argiriou A, Vitale D, Liguori R, Piravandi E, Massenet O, Quigley F, Clabauld G, Mundlein A, Felber R, Schnabl S, Hiller R, Schmidt W, Lecharny A, Aubourg S, Chefdor F, Cooke R, Berger C, Montfort A, Casacuberta E, Gibbons T, Weber N, Vandenbol M, Bargues M, Terol J, Torres A, Perez-Perez A, Purnelle B, Bent E, Johnson S, Tacon D, Jesse T, Heijnen L, Schwarz S, Scholler P, Heber S, Francs P, Bielke C, Frishman D, Haase D, Lemcke K, Mewes HW, Stocker S, Zaccaria P, Bevan M, Wilson RK, de la Bastide M, Habermann K, Parnell L, Dedhia N, Gnoj L, Schutz K, Huang E, Spiegel L, Sehkon M, Murray J, Sheet P, Cordes M, Abu-Threideh J, Stoneking T, Kalicki J, Graves T, Harmon G, Edwards J, Latreille P, Courtney L, Cloud J, Abbott A, Scott K, Johnson D, Minx P, Bentley D, Fulton B, Miller N, Greco T, Kemp K, Kramer J, Fulton L, Mardis E, Dante M, Pepin K, Hillier L, Nelson J, Spieth J, Ryan E, Andrews S, Geisel C, Layman D, Du H, Ali J, Berghoff A, Jones K, Drone K, Cotton M, Joshu C, Antonoiu B, Zidanic M, Strong C, Sun H, Lamar B, Yordan C, Ma P, Zhong J, Preston R, Vil D, Shekher M, Matero A, Shah R, Swaby IK, O'Shaughnessy A, Rodriguez M, Hoffmann J, Till S, Granat S, Shohdy N, Hasegawa A, Hameed A, Lodhi M, Johnson A, Chen E, Marra M, Martienssen R, McCombie WR: Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana. Nature. 1999 Dec 16;402(6763):769-77. doi: 10.1038/47134.
Pubmed: 10617198
Pineau B, Layoune O, Danon A, De Paepe R: L-galactono-1,4-lactone dehydrogenase is required for the accumulation of plant respiratory complex I. J Biol Chem. 2008 Nov 21;283(47):32500-5. doi: 10.1074/jbc.M805320200. Epub 2008 Sep 17.
Pubmed: 18799460
Jespersen HM, Kjaersgard IV, Ostergaard L, Welinder KG: From sequence analysis of three novel ascorbate peroxidases from Arabidopsis thaliana to structure, function and evolution of seven types of ascorbate peroxidase. Biochem J. 1997 Sep 1;326 ( Pt 2):305-10. doi: 10.1042/bj3260305.
Pubmed: 9291097
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