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|
Expected Taxonomic Range: Magnoliophyta
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 [Muller98a] 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 [Wang12d] [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] [Li10c]. 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 [Park12].
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 [Li12a]. 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-β-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
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
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
Li10c: 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
Li12a: 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
Park12: 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.
Wang12d: 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
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
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.
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
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
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
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