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MetaCyc Pathway: rutin biosynthesis

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. 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 ? : Dimorphandra mollis , Fagopyrum esculentum , Fagopyrum tataricum , Vigna radiata radiata

Expected Taxonomic Range: Magnoliophyta

Summary:
General Background

Rutin is a flavonol glucoside that is widespread in the plant kingdom, and has been especially found in the Polygonaceae and Fabaceae families. Rutin has several interesting pharmacological properties (e.g. antioxidative activity) that have been exploited in human medicine and nutrition. Quercetin-3-rhamnoside and its rutinoside, i.e. rutin has been demonstrated to possess antimalarial activity [Iwu86]. Rutin was identified as one of the most active agents of an aqueous crude extract of Baccharis trimera that was shown to express strong anti-inflammatory and analgesic properties [Gene96]. The inhibitory effect against non-enzymatic lipid peroxidation, deoxyribose degradation [Muller98] and on lipopolysaccharide-induced NO production [Shen02] emphasizes the biological relevance of rutin in the treatment of related human conditions. Moreover, rutin has been shown to be a promising agent against Alzheimer's disease [Wang12a] [Javed12], provides resistance to biotrophic and necrotrophic pathogens [Kroner12] and showed protective effect against pro-carcinogenic agents [Cristina11].

Rutin production in plants has been found to be increased under the influence of UV-B radiation. Ambient radiation was the most effective mean to elevate rutin content, especially in leaves, indicating a possible involvement into UV protection [Kreft02]. The high accumulation of rutin in the upper epidermis of leaves in Fagopyrum species also supports its possible role as UV screen [Margna90]. Rutin content in plants also seems to be influenced by the photoperiod as it was promoted under far red (FR) conditions with no obvious changes in the overall production of phenolics [Tso70].

About This Pathway

This pathway mostly describes the metabolic situation found in buckwheat species and represents a branch of the phenylpropanoid biosynthesis (see also flavonoid biosynthesis, flavonol biosynthesis and quercetin glycoside biosynthesis (Arabidopsis)). This has been demonstrated through monitoring the differential expression of involved genes during developmental stages of buckwheat which are characterized by the accumulation of rutin as one of the most abundant flavonol glycoside in this plant [Gupta11] [Li10a]. The increased production of rutin after overexpressing the flavonol-specific transcription factor AtMYB12 in Fagopyrum esculentum and observing the expression of genes presumably involved in rutin biosynthesis shows that key enzymes of the phenylpropanoid and flavonoid biosynthetic pathways up to phenylpropanoid biosynthesis, initial reactions are channeled towards rutin formation [Park12a].

An important metabolic step in this pathway is carried out by the flavonol synthase catalyzing the 2-oxoglutarate dependent oxygenation of (+)-taxifolin to form quercetin. The corresponding gene has been cloned, heterologously expressed and characterized with regard to protein structure and catalytic properties [Li12]. The following conversion in the pathway forming the immediate precursor for rutin, quercetin-3-glucoside (isoquercetin) is realized by the flavonol 3-O-glucosyltransferase [Suzuki05a] [Lucci09] (compare also quercetin glycoside biosynthesis (Arabidopsis)). The enzyme catalyzing the final step in the pathway, i.e. flavonol-3-O-glucoside L-rhamnosyltransferase has been partially purified from mung bean [Barber62] and Dimorphandra mollis (fava d'anta) [Lucci09]. The enzyme catalyzes the transfer of a rhamnosyl group from UDP-L-rhamnose to quercetin 3-O-glucoside forming rutin. Although dTDP-rhamnose had been considered as the primary donor [Barber62] it has been demonstrated that UDP-L-rhamnose is the native donor for the transfer of L-rhamnose [Barber91] [Barber63].

It had long been a pending question how exactly UDP-L-rhamnose was biosynthesized in plants. It is clear now that UDP-L-rhamnose can be catalyzed from UDP-D-glucose (see UDP-L-rhamnose biosynthesis) [Barber91] [Barber63] which is an ubiquitous activated nucleotide sugar readily available for metabolic processes in plants.

Superpathways: superpathway of flavones and derivatives biosynthesis

Credits:
Created 02-Nov-2006 by Foerster H , TAIR
Revised 11-Oct-2012 by Foerster H , Boyce Thompson Institute


References

Barber62: Barber GA (1962). "Enzymic glycosylation of quercetin to rutin." Biochemistry 1;463-8. PMID: 13864833

Barber63: Barber GA (1963). "The formation of uridine diphosphate L-rhamnose by enzymes of the tobacco leaf." Arch Biochem Biophys 103;276-82. PMID: 14084592

Barber91: Barber GA, Behrman EJ (1991). "The synthesis and characterization of uridine 5'-(β-L-rhamnopyranosyl diphosphate) and its role in the enzymic synthesis of rutin." Arch Biochem Biophys 288(1);239-42. PMID: 1898019

Cristina11: Cristina Marcarini J, Ferreira Tsuboy MS, Cabral Luiz R, Regina Ribeiro L, Beatriz Hoffmann-Campo C, Segio Mantovani M (2011). "Investigation of cytotoxic, apoptosis-inducing, genotoxic and protective effects of the flavonoid rutin in HTC hepatic cells." Exp Toxicol Pathol 63(5);459-65. PMID: 20399630

Gene96: Gene RM, Cartana C, Adzet T, Marin E, Parella T, Canigueral S (1996). "Anti-inflammatory and analgesic activity of Baccharis trimera: identification of its active constituents." Planta Med 62(3);232-5. PMID: 8693035

Gupta11: Gupta N, Sharma SK, Rana JC, Chauhan RS (2011). "Expression of flavonoid biosynthesis genes vis-a-vis rutin content variation in different growth stages of Fagopyrum species." J Plant Physiol 168(17);2117-23. PMID: 21872967

Iwu86: Iwu MM, Obidoa O, Anazodo M (1986). "Biochemical mechanism of the antimalarial activity of Azadirachta indica leaf extract." Pharmacol Res Commun 18(1);81-91. PMID: 3081917

Javed12: Javed H, Khan MM, Ahmad A, Vaibhav K, Ahmad ME, Khan A, Ashafaq M, Siddiqui MS, Safhi MM, Islam F (2012). "Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type." Neuroscience 210;340-52. PMID: 22441036

Kreft02: Kreft S, Strukelj B, Gaberscik A, Kreft I (2002). "Rutin in buckwheat herbs grown at different UV-B radiation levels: comparison of two UV spectrophotometric and an HPLC method." J Exp Bot 53(375);1801-4. PMID: 12147730

Kroner12: Kroner A, Marnet N, Andrivon D, Val F (2012). "Nicotiflorin, rutin and chlorogenic acid: phenylpropanoids involved differently in quantitative resistance of potato tubers to biotrophic and necrotrophic pathogens." Plant Physiol Biochem 57;23-31. PMID: 22677447

Li10a: Li X, Park NI, Xu H, Woo SH, Park CH, Park SU (2010). "Differential Expression of Flavonoid Biosynthesis Genes and Accumulation of Phenolic Compounds in Common Buckwheat (Fagopyrum esculentum)." J Agric Food Chem. PMID: 21062042

Li12: Li C, Bai Y, Li S, Chen H, Han X, Zhao H, Shao J, Park SU, Wu Q (2012). "Cloning, characterization, and activity analysis of a flavonol synthase gene FtFLS1 and its association with flavonoid content in tartary buckwheat." J Agric Food Chem 60(20);5161-8. PMID: 22563787

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.

Margna90: Margna U, Margna E, Paluteder A (1990). "Localization and distribution of flavonoids in buckwheat seedling cotyledons." J. Plant Physiol. 136: 166-171.

Muller98: Muller K, Ziereis K, Paper DH (1998). "Ilex aquifolium: protection against enzymatic and non-enzymatic lipid peroxidation." Planta Med 64(6);536-40. PMID: 9741300

Park12a: Park NI, Li X, Thwe AA, Lee SY, Kim SG, Wu Q, Park SU (2012). "Enhancement of rutin in Fagopyrum esculentum hairy root cultures by the Arabidopsis transcription factor AtMYB12." Biotechnol Lett 34(3);577-83. PMID: 22113884

Shen02: Shen SC, Lee WR, Lin HY, Huang HC, Ko CH, Yang LL, Chen YC (2002). "In vitro and in vivo inhibitory activities of rutin, wogonin, and quercetin on lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production." Eur J Pharmacol 446(1-3);187-94. PMID: 12098601

Suzuki05a: 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.

Tso70: Tso TC, Kasperbauer MJ, Sorokin TP (1970). "Effect of photoperiod and end-of-day light quality on alkaloids and phenolic compounds of tobacco." Plant Physiol 45(3);330-3. PMID: 5423471

Wang12a: Wang SW, Wang YJ, Su YJ, Zhou WW, Yang SG, Zhang R, Zhao M, Li YN, Zhang ZP, Zhan DW, Liu RT (2012). "Rutin inhibits β-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines." Neurotoxicology 33(3);482-90. PMID: 22445961

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

Bredebach11: Bredebach M, Matern U, Martens S (2011). "Three 2-oxoglutarate-dependent dioxygenase activities of Equisetum arvense L. forming flavone and flavonol from (2S)-naringenin." Phytochemistry 72(7);557-63. PMID: 21353683

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

Kim06b: 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.

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

Lukacin03: Lukacin R, Wellmann F, Britsch L, Martens S, Matern U (2003). "Flavonol synthase from Citrus unshiu is a bifunctional dioxygenase." Phytochemistry 62(3);287-92. PMID: 12620339

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

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

Prescott02: Prescott AG, Stamford NP, Wheeler G, Firmin JL (2002). "In vitro properties of a recombinant flavonol synthase from Arabidopsis thaliana." Phytochemistry 2002;60(6);589-93. PMID: 12126705

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.

Wellmann02: Wellmann F, Lukacin R, Moriguchi T, Britsch L, Schiltz E, Matern U (2002). "Functional expression and mutational analysis of flavonol synthase from Citrus unshiu." Eur J Biochem 269(16);4134-42. PMID: 12180990

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

Xu08: Xu F, Cheng H, Cai R, Li LL, Chang J, Zhu J, Zhang FX, Chen LJ, Wang Y, Cheng SH, Cheng SY (2008). "Molecular cloning and function analysis of an anthocyanidin synthase gene from Ginkgo biloba, and its expression in abiotic stress responses." Mol Cells 26(6);536-47. PMID: 18779661


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 Fri Dec 19, 2014, BIOCYC14B.