Disease relevance of Flavonol

• Flavonol-stimulated efflux of 7,12-dimethylbenz(a)anthracene in multidrug-resistant breast cancer cells [1].
• To determine the domain responsible for the properties of the flavonol STs, several chimeric flavonol STs were constructed by the reciprocal exchange of DNA fragments derived from the plasmids pFST3 and pFST4' and by the expression of the corresponding chimeric proteins in Escherichia coli [2].
• After adjustment for tea consumption and flavonol intake, a 7.5-mg increase in catechin intake from sources other than tea was associated with a tendency for a 20% reduction in ischemic heart disease mortality risk (P = 0.114) [3].
• In a large US cohort, a protective effect was only found in a subgroup with previous history of coronary heart disease, whereas in Welsh men, flavonol intake, mainly from tea, was associated with an increased risk of coronary heart disease [4].
• In the multivariate model, the relative risk of nonfatal myocardial infarction was 0.77 (95% confidence interval = 0.64-0.93) among men in the highest (median 18 mg per day) compared with the lowest (median 4 mg per day) quintile of flavonol and flavone intake [5].

High impact information on Flavonol

• Levels of genistein were not increased by expressing both IFS and alfalfa chalcone isomerase, but levels of flavonol conjugates were reduced to a greater extent than could be accounted for by flux into isoflavone [6].
• As a result of a van der Waals contact between the most outward flavonol A-ring and Pro(164), a flexible loop in front of the active site becomes partly ordered [7].
• Affinity chromatography and immunoprecipitation assays further demonstrated interactions between chalcone synthase, CHI, and flavonol 3-hydroxylase in lysates from Arabidopsis seedlings [8].
• Energy transfer to a proton-transfer fluorescence probe: tryptophan to a flavonol in human serum albumin [9].
• The two flavonol STs of F. chloraefolia also shared significant sequence similarities with steroid and aryl STs found in animal tissues and with the senescence marker protein 2 isolated from rat liver, suggesting an evolutionary link between plant and animal STs [10].

Chemical compound and disease context of Flavonol

• 40 compounds structurally related to the plant flavonol quercetin were tested for mutagenic activity in Salmonella typhimurium strain TA98 [11].
• In our search for novel dietary anticarcinogens, fisetin, a flavonol widely distributed in fruits and vegetables was found to induce QR activity in murine hepatoma 1c1c7 cells [12].
• This study was conducted to evaluate the effects of the prenylated flavonol artocarpin from the heartwood of Artocarpus incisus on ultraviolet (UV)-induced hyperpigmentation of guinea pig skin [13].
• Introduction into the E. coli cells of the flavanone 3beta-hydroxylase and flavonol synthase genes from the plant Citrus species led to production of flavonols: kaempferol (15.1 mg/l) from tyrosine and galangin (1.1 mg/l) from phenylalanine [14].
• A new flavonol glycoside gallate ester from Acer okamotoanum and its inhibitory activity against human immunodeficiency virus-1 (HIV-1) integrase [15].

Biological context of Flavonol

• Based on sequence homology, the plant ST coding sequences are grouped under the SULT3 family, also known as the flavonol ST family [16].
• The pFST3 and pFST4' cDNAs encode flavonol sulfotransferases (ST) that are 69% identical in amino acid sequence yet exhibit strict substrate and position specificities [2].
• In this study, flavonol glycosyltransferases were considered in a functional genomics approach aimed at revealing genes involved in determining the flavonol-glycoside profile [17].
• In this combination, the isoflavone genistein, the flavone apigenin, and the flavonol quercetin caused an enhancement of radiation-induced cell death [18].
• In pistils of potato, pollen tube growth induced an increase in fls gene expression that, unlike the situation in pollinated pistils of petunia, did not result in an increased flavonol content [19].

Anatomical context of Flavonol

• Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils [20].
• In summary, quercetin, a natural flavonol widely distributed in the human diet, inhibits NO production in IL-1beta-stimulated hepatocytes through the inhibition of iNOS expression [21].
• Flavonol concentrations were determined in plasma, ileal and cecal contents, and feces [22].
• Flavone and flavonol glucosides and their corresponding aglycones are glucuronidated during transfer across the rat jejunum and ileum and this glucuronidation occurs without the need for gut microflora [23].
• We evaluated the ability of a synthetic flavonol, 3',4'-dihydroxyflavonol (DiOHF) to scavenge superoxide in post-I/R myocardium and to prevent myocardial I/R injury [24].

Associations of Flavonol with other chemical compounds

• A flavonol sulfotransferase (EC 2.8.2.-), which catalyzes the transfer of the sulfate group from 3'-phosphoadenosine 5'-phosphosulfate to the 3-hydroxyl group of flavonol aglycones, has been purified to apparent homogeneity from Flaveria chloraefolia [25].
• Quercetin, a major flavonol in the diet, inhibits lens opacification in a lens organ culture oxidative model of cataract [26].
• Here, we identified the Arabidopsis (Arabidopsis thaliana) R2R3-MYB transcription factor MYB12 as a flavonol-specific activator of flavonoid biosynthesis [27].
• Expression of genes involved in anthocyanin biosynthesis in relation to anthocyanin, proanthocyanidin, and flavonol levels during bilberry fruit development [28].
• Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis [29].
• Glutathione S-transferasefused recombinant UGT89C1 protein converted kaempferol 3-O-glucoside to kaempferol 3-O-glucoside-7-O-rhamnoside and recognized 3-O-glycosylated flavonols and UDP-rhamnose as substrates, but not flavonol aglycones, 3-O-glycosylated anthocyanins or other UDP-sugars [30].

Gene context of Flavonol

• We describe here the crystal structure of human CDK6 in complex with a viral cyclin and a flavonol inhibitor, fisetin [31].
• Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1 (apparent K(i) = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent K(i) = 418 +/- 50 nM) [32].
• G. biloba extract of known abundance of terpene trilactones and flavonol glycosides inhibited 7-ethoxyresorufin O-dealkylation catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2, and human liver microsomes, with apparent K(i) values of 2 +/- 0.3, 5 +/- 0.5, 16 +/- 1.4, and 39 +/- 1.2 mug/ml (mean +/- SE), respectively [32].
• The Arabidopsis transcription factor MYB12 is a flavonol-specific regulator of phenylpropanoid biosynthesis [27].
• Apigenin and 3-hydroxyflavone further decreased TIMP-1 expression below basal level and completely abolished TIMP-2 expression [33].
• In developing seedlings, MYB11, MYB12 and MYB111 act in an additive manner due to their differential spatial activity; MYB12 controls flavonol biosynthesis mainly in the root, while MYB111 controls flavonol biosynthesis primarily in cotyledons [34].
• The strict substrate specificity of UGT78D3 for flavonol aglycones and UDP-arabinose indicate that UGT78D3 is a flavonol arabinosyltransferase [35].

Analytical, diagnostic and therapeutic context of Flavonol

• Fasting plasma flavonol concentrations (measured by high-performance liquid chromatography) were 5.6 +/- 2.9 ng/ml on the low-flavonol diet and increased 12-fold to 72.1 +/- 15.8 ng/ml on the high-flavonol diet (P < 0.001) [36].
• In this study, the function of amino acid residues within these two regions was investigated by site-directed mutagenesis of the plant flavonol 3-ST [37].
• We conclude that flavonols in plasma and urine reflect short-term flavonol intake and that they could be used as biomarkers to distinguish between high and low flavonol consumption in epidemiologic studies [38].
• The latter enzyme also glycosylated certain isoflavones and the flavonol quercetin with higher efficiency than triterpenes; however, integrated transcript and metabolite profiling supported a function for UGT71G1 in terpenoid but not (iso)flavonoid biosynthesis in the elicited cell cultures [39].
• 3'-Phosphoadenosine 5'-phosphosulfate binding site of flavonol 3-sulfotransferase studied by affinity chromatography and 31P NMR [40].

References