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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: quercetin glycoside biosynthesis (Arabidopsis)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Phenylpropanoid Derivatives Biosynthesis Flavonoids Biosynthesis Flavonols Biosynthesis

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col

Expected Taxonomic Range: Brassicaceae

Summary:
General Background

Flavonole such as quercetin and its glycosidic derivatives (this pathway) and kaempferol/kaempferol glycoside (compare kaempferol glycoside biosynthesis (Arabidopsis)) are the major flavonoids found in Arabidopsis thaliana [Veit99] [Kerhoas06]. Metabolic mutants of Arabidopsis were found to express a different profile of flavonols emphasizing the value of metabolic profiling for the exploration of the underlying pathways [Graham98].

The occurrence of the two main flavonols kaempferol and quercetin is predominant in different tissues. Quercetin appears to be the main flavonoid in seeds and kaempferol is more prominent in flowers of Arabidopsis [Pelletier97, Shirley95]. Beside the glycosylated monomeric flavonols, dimers and oligomers of flavonols have been identified in Arabidopsis which again accumulate in a spatially and temporally controlled manner that is dependent of seed development and maturation of seeds [Routaboul06].

The biological function of flavonoids including flavonols such as UV-protection, defense and resistance against biological and non-biological agents and interacting with plant hormones [WinkelShirley02] has been investigated in depth. However, flavonols also have a significant impact on human health as that they are an important component of the daily diet. Flavonols are involved in the prevention of cancer and cardiovascular diseases that have attracted researchers to reveal the causal molecular principles [Graf05, Kanadaswami].

About This Pathway

Glycosylation is one of the most widespread modifications of plant secondary metabolites that can alter properties and functions of the modified compound. 120 putative UDP-glucose: glycosyltransferases alone have been predicted from the genome of Arabidopsis but for only a few their molecular function has been verified experimentally [Gachon05].

The metabolic steps that generate glycosides of quercetin are catalyzed by enzymes that express broader substrate specificity and usually accept kaempferol and/or isorhamnetin to a comparable degree. In general, flavonols are preferred over flavones and flavanones [Willits04] [Jones03] matching the flavonoid composition found in Arabidopsis.

The glycosyltransferases acting in Arabidopsis thaliana have been demonstrated to preferentially transport sugars to the 3-OH and 7-OH position of the C and the A-ring of the flavonol, respectively. The enzymes catalyzing the 3-O and 7-O--glucosylation have been purified from Arabidopsis [Kim06a] [Kim06] [Willits04]. Quercetin and kaempferol-3-rhamnoside are the most abundant flavonols reported and the corresponding enzymes have been purified and characterized via a functional genomic approach just recently [Jones03]. The quercetin biosynthesis as displayed reflects the currently known enzymatic steps and the results of metabolic profiling [Kerhoas06, Routaboul06] but some of the enzymes catalyzing the formation of e.g. quercetin-3,5-diglucoside remain to be characterized.The identification of the flavonol 7-O-rhamnosyltransferase responsible for the formation of major kaempferol and quercetin glycosides in Arabidopsis has been achieved by utilizing transcriptome expression analysis. The molecular function of the flavonol 7-O-rhamnosyltransferase (UGT89C1) was confirmed through T-DNA mutants knocked out for the UGT89C1 in which rhamnosylated flavonols could not be found in the metabolic profile. In addition, the recombinant expressed GST-fusion protein demonstrated the very specific 7-rhamnosylation for flavonol mono- and diglucosides [YonekuraSakakib07]. The enzymes catalyzing the steps leading to the generation of the precursor compounds quercetin 3-O-sophoroside and quercetin-3-gentiobioside have not yet been identified and remain to be shown.

Superpathways: superpathway of flavones and derivatives biosynthesis

Unification Links: AraCyc:PWY-5321

Credits:
Created 08-Sep-2006 by Foerster H , TAIR
Revised 19-Dec-2012 by Foerster H , Boyce Thompson Institute


References

Gachon05: Gachon CM, Langlois-Meurinne M, Saindrenan P (2005). "Plant secondary metabolism glycosyltransferases: the emerging functional analysis." Trends Plant Sci 10(11);542-9. PMID: 16214386

Graf05: Graf BA, Milbury PE, Blumberg JB (2005). "Flavonols, flavones, flavanones, and human health: epidemiological evidence." J Med Food 8(3);281-90. PMID: 16176136

Graham98: Graham TL (1998). "Flavonoid and flavonol glycoside metabolism in Arabidopsis." Plant Physiol. Biochem., 36 (l-2). 135-144.

Jones03: Jones P, Messner B, Nakajima J, Schaffner AR, Saito K (2003). "UGT73C6 and UGT78D1, glycosyltransferases involved in flavonol glycoside biosynthesis in Arabidopsis thaliana." J Biol Chem 278(45);43910-8. PMID: 12900416

Kanadaswami: Kanadaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT, Lee MT "The antitumor activities of flavonoids." In Vivo 19(5);895-909. PMID: 16097445

Kerhoas06: Kerhoas L, Aouak D, Cingoz A, Routaboul JM, Lepiniec L, Einhorn J, Birlirakis N (2006). "Structural characterization of the major flavonoid glycosides from Arabidopsis thaliana seeds." J Agric Food Chem 54(18);6603-12. PMID: 16939316

Kim06: Kim JH, Kim BG, Park Y, Ko JH, Lim CE, Lim J, Lim Y, Ahn JH (2006). "Characterization of flavonoid 7-O-glucosyltransferase from Arabidopsis thaliana." Biosci Biotechnol Biochem 70(6);1471-7. PMID: 16794327

Kim06a: Kim JH, Kim BG, Ko JH, Lee Y, Hur H-G, Lim Y, Ahn J-H (2006). "Molecular cloning, expression, and characterization of a flavonoid glycosyltransferase from Arabidopsis thaliana." Plant Science, 170(4), 897-903.

Pelletier97: Pelletier MK, Murrell JR, Shirley BW (1997). "Characterization of flavonol synthase and leucoanthocyanidin dioxygenase genes in Arabidopsis. Further evidence for differential regulation of "early" and "late" genes." Plant Physiol 1997;113(4);1437-45. PMID: 9112784

Routaboul06: Routaboul JM, Kerhoas L, Debeaujon I, Pourcel L, Caboche M, Einhorn J, Lepiniec L (2006). "Flavonoid diversity and biosynthesis in seed of Arabidopsis thaliana." Planta 224(1);96-107. PMID: 16395586

Shirley95: Shirley BW, Kubasek WL, Storz G, Bruggemann E, Koornneef M, Ausubel FM, Goodman HM (1995). "Analysis of Arabidopsis mutants deficient in flavonoid biosynthesis." Plant J 8(5);659-71. PMID: 8528278

Veit99: Veit M, Pauli GF (1999). "Major flavonoids from Arabidopsis thaliana leaves." J Nat Prod 1999;62(9);1301-3. PMID: 10514319

Willits04: Willits MG, Giovanni M, Prata RT, Kramer CM, De Luca V, Steffens JC, Graser G (2004). "Bio-fermentation of modified flavonoids: an example of in vivo diversification of secondary metabolites." Phytochemistry 65(1);31-41. PMID: 14697269

WinkelShirley02: Winkel-Shirley B (2002). "Biosynthesis of flavonoids and effects of stress." Curr Opin Plant Biol 5(3);218-23. PMID: 11960739

YonekuraSakakib07: Yonekura-Sakakibara K, Tohge T, Niida R, Saito K (2007). "Identification of a flavonol 7-O-rhamnosyltransferase gene determining flavonoid pattern in Arabidopsis by transcriptome coexpression analysis and reverse genetics." J Biol Chem 282(20);14932-41. PMID: 17314094

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

FukuchiMitzutan11: Fukuchi-Mitzutani M, Akagi M, Ishiguro K, Katsmoto Y, Fukui Y, Togami J (2011). "Biochemical and molecular characterization of anthocyanidin/flavonol 3-glucosylation pathways in Rosa x hybrida." Plant Biotechnology 28: 239-244.

Jourdan82: Jourdan PS, Mansell RL (1982). "Isolation and partial characterization of three glucosyl transferases involved in the biosynthesis of flavonol triglucosides in Pisum sativum L." Arch Biochem Biophys 213(2);434-43. PMID: 6462109

Kramer03: Kramer CM, Prata RT, Willits MG, De Luca V, Steffens JC, Graser G (2003). "Cloning and regiospecificity studies of two flavonoid glucosyltransferases from Allium cepa." Phytochemistry 64(6);1069-76. PMID: 14568073

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lazarowski03: Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003). "Release of cellular UDP-glucose as a potential extracellular signaling molecule." Mol Pharmacol 63(5);1190-7. PMID: 12695547

Lim02: Lim EK, Doucet CJ, Li Y, Elias L, Worrall D, Spencer SP, Ross J, Bowles DJ (2002). "The activity of Arabidopsis glycosyltransferases toward salicylic acid, 4-hydroxybenzoic acid, and other benzoates." J Biol Chem 277(1);586-92. PMID: 11641410

Lim04: Lim EK, Ashford DA, Hou B, Jackson RG, Bowles DJ (2004). "Arabidopsis glycosyltransferases as biocatalysts in fermentation for regioselective synthesis of diverse quercetin glucosides." Biotechnol Bioeng 87(5);623-31. PMID: 15352060

Lim05: Lim, E.-K., Doucet, C.J., Hou, B., Jackson, R.G., Abrams, S.R., Bowles, D.J. (2005). "Resolution of (+)-abscisic acid using an Arabidopsis glycosyltransferase." Tetrahedron: Asymmetry 16:143-147.

Lucci09: Lucci N, Mazzafera P (2009). "Rutin synthase in fava d'anta: Purification and influence of stressors." Canadian Journal of Plant Science 89: 895-902.

Masada09: Masada S, Terasaka K, Oguchi Y, Okazaki S, Mizushima T, Mizukami H (2009). "Functional and structural characterization of a flavonoid glucoside 1,6-glucosyltransferase from Catharanthus roseus." Plant Cell Physiol 50(8);1401-15. PMID: 19561332

Oguchi07: Oguchi Y, Masada S, Kondo T, Terasaka K, Mizukami H (2007). "Purification and characterization of UDP-glucose : curcumin glucoside 1,6-glucosyltransferase from Catharanthus roseus cell suspension cultures." Plant Cell Physiol 48(11);1635-43. PMID: 17940060

Owens: Owens DK, McIntosh CA "Identification, recombinant expression, and biochemical characterization of a flavonol 3-O-glucosyltransferase clone from Citrus paradisi." Phytochemistry 70(11-12);1382-91. PMID: 19733370

Schlangen09: Schlangen K, Miosic S, Castro A, Freudmann K, Luczkiewicz M, Vitzthum F, Schwab W, Gamsjager S, Musso M, Halbwirth H (2009). "Formation of UV-honey guides in Rudbeckia hirta." Phytochemistry 70(7);889-98. PMID: 19477473

Stich: Stich K, Halbwirth H, Wurst F, Forkmann G "UDP-glucose: flavonol 7-O-glucosyltransferase activity in flower extracts of Chrysanthemum segetum." Z Naturforsch C 52(3-4);153-8. PMID: 9167271

Suzuki05: Suzuki T, Kim S-J, Yamauchi H, Takigawa A, Honda Y, Mukasa Y (2005). "Characterization of a flavonoid 3-O-glucosyltransferase and its activity during cotyledon growth in buckwheat (Fagopyrum esculentum)." Plant Science 169: 943-948.

Trapero12: Trapero A, Ahrazem O, Rubio-Moraga A, Jimeno ML, Gomez MD, Gomez-Gomez L (2012). "Characterization of a glucosyltransferase enzyme involved in the formation of kaempferol and quercetin sophorosides in Crocus sativus." Plant Physiol 159(4);1335-54. PMID: 22649274

Tsushida96: Tsushida, T., Suzuki M. (1996). "Content of flavonol glucosides and some properties of enzymes metabolizing the glucosides in onion. Flavonoid in fruits and vegetables, part II." Jpn Food Sci Technol 43:642-649.


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Wed Nov 26, 2014, BIOCYC14B.