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Flavonoid

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Contents 1 Class Overview 2 Biosynthesis 3 Bioactivity 3.1 Tea Related 3.2 General Flavonoid 4 Bioavailability 5 Representative Names 6 Database statistics/ranking 7 Flavonoid content in food 8 Design of Flavonoid ID numbers 8.1 For Users of Flavonoid Viewer

Class Overview

The word "flavonoid" comes from its Latin origin flavus (yellow) with oid, meaning yellow-ish. It comes from its history as yellow natural dye (quercetin and kaempferol are the most widespread flavone dyes. See flavone).
Chemically speaking, it is a class of plant secondary metabolites that have two benzene rings (each called A-ring and B-ring) connected by a chain of three carbons (Figure 1). The carbon chain, corresponding to the numbers 2,3,4 in Figure 1, is linked to a hydroxyl group in the A-ring to form the C-ring. The class of flavonoids are usually determined by the modification pattern of the C-ring (Table 1).
Flavonoid is utilized in many industrial processes from pigments to food additives. Often heard names include anthocyanin, catechin, flavan, and isoflavone.

Table 1. Flavonoid Classification

1st Class
FL1: Anthochlor (Aurone and Chalcone) オーロン、カルコン safflower yellow 紅花（末摘花）の黄色	FL2: Flavanone フラバノン white skin of orange みかんジュースの白沈	FL3: Flavone フラボン herbs like parsley セロリやパセリ等ハーブ
2nd Class FL1A Aurone FL1B Auronol FL1C Chalcone FL1D Dihydrochalcone	FL2F: Flavanone	FL3F: Flavone
FL4: Dihydroflavonol ジヒドロフラボノール antioxidant in grapes ブドウの抗酸化成分	FL5: Flavonol フラボノール vegetables such as onion たまねぎ等多くの野菜	FL6: Flavan Leucoanthocyanidin フラバン tea, cocoa お茶、ココア
FL4D: Dihydroflavonol	FL5F: Flavonol	2nd Class FL6F Flavan FL63 Flavan 3-ol FL64 Flavan 4-ol FL6D Flavan 3,4-diol
FL7: Anthocyani(di)n アントシアニ(ジ)ン purple vegetables/fruits (赤)紫の野菜、果物	FLI: Isoflavonoid イソフラボノイド beans 豆類	FLN: Neoflavonoid ネオフラボノイド
2nd Class FL7A Anthocyanin FL7D 3-Deoxyanthocyanin	2nd Class FLIA Isoflavone FLIB Isoflavanone FLIC Isoflavan FLID Pterocarpane FLIE Coumestan FLIF Rotenoid FLIG Coumaranochromone FLIH 3-Arylcoumarin FLII 2-Arylbenzofuran FLIJ alpha-Methoxynbenzoin	2nd Class FLNA 4-Arylcoumarin FLNB 4-Arylchroman FLNC Dalbergiquinol FLND Dalbergione FLNE Neoflavene FLNF Coumarinic acid

Biosynthesis

Flavonoid is synthesized through both the phenylpropanoid-acetate pathway and the acetate-malonate pathway in all higher plants (but not algae). Most plants contain the 7 major subgroups (chalcones, flavanones, flavones, flavonols, flavans, anthocyanidins, and anthycyanins), but aurones　or isoflavonoids are not ubiquitous.

4-coumaroyl CoA + malonyl CoA

CHS

CHALCONES, AURONES

chalconaringenin

FLAVONES

CHI (isomerase)

FS (oxygenase)

IFS

naringenin FLAVANONE

kaempferol

FLAVONOLS

quercetin

myricetin

ISO-FLAVONES

F3H (hydroxylase)

FLS (oxygenase)

FLS

FLS

DIHYDRO FLAVONOLS

dihydro-kaempferol

F3'H +OH in B-ring

dihydro-quercetin

F3'5'H +OH in B-ring

dihydro-myricetin

DFR (reductase)

DFR

DFR

flavan diol LEUCOANTHO-CYANIDINS

leuco-pelargonidin

(reductase) LAR

leuco-cyanidin

LAR

leuco-delphinidin

LAR

LDOX (oxygenase)

PROANTHO- CYANIDINS *

LDOX

PROANTHO- CYANIDINS *

LDOX

*...polymers of flavanols

ANTHO-CYANIDINS

pelargonidin

ANR

cyanidin

ANR

delphinidin

ANR

UF3GT (+sugar)

epi-afzelechin

UF3GT

epi-catechin

UF3GT

epigallo-catechin

FLAVAN 3-OLS

ANTHO-CYANINS

pelargonidin 3-glucoside

cyanidin 3-glucoside

delphinidin 3-glucoside

UF5GT, AOMT etc.

UF5GT, AOMT etc.

UF5GT, AOMT etc.

Information for the Above Abbreviated Gene Names
Six Structural Genes
Abbrev.	Name	Origin	Information
CHS	chalcone synthase	Bacterial polyketide synthases, particularly those in fatty acid synthesis (Verwoert et al. 1992)	Early response against light [1] [2]
CHI	chalcone-flavanone isomerase	Unclear and unique to plants.[3] Eubacterium ramulus has the CHI activity. [4]	Early response against light.
F3H	flavanone 3-hydroxylase	2-oxoglutarate-dependent dioxygenase family [5]	Early response in Arabidopsis but late in Antirrhinum [6]
FLS	flavonol synthase	2-oxoglutarate-dependent dioxygenase family [7]	Early response against light. In Arabidopsis, all structural genes are single-copy except for this one, to which six genes exist and two of them are not expressed.
DFR	dihydroflavonol 4-reductase	NADPH-dependent reductase associated with steroid metabolism [8]	Later response
ANS/LDOX	anthocyanidin synthase or leucoanthocyanidin dioxygenase	2-oxoglutarate-dependent dioxygenase family	Later response
Auxiliary Genes
F3'H	flavonoid 3'-hydroxylase	cytochrome P450 hydroxylase family [9]
F3'5'H	flavonoid 3',5'-hydroxylase	cytochrome P450 hydroxylase family [10]	Not reported in mosses or liverworts. The transformation of the F3'5'H and the cytochrome b5 gene of petunia into carnation changed its flower color deep purple.[11][12]
FSI	flavone synthase	Dioxygenase in parsley (FSI) and P450 monooxygenase in snapdragon (FSII).
LAR (or LCR)	leucoanthocyanidin reductase
UF3GT	UDP flavonoid glucosyltransferase
GST	glutathione-S-transferase		Transport of flavonoids from cytoplasm to vacuole or cell walls requires both GST and the glutathione pump in ATP-binding cassette family.[13][14]
AOMT	anthocyanin O-methyl transferase
↑ Kubasek WL, Shirley BW, McKillop A, Goodman HM, Briggs W, Ausubel FM: Regulation of flavonoid biosynthetic genes in germinating Arabidopsis seedlings. Plant Cell 1992 4:1229-1236 ↑ Pelletier MK, Murrell JR, Shirley BW: Characterization of flavonol synthase and leucoanthocyanidins dioxygenase genes in Arabidopsis. Plant Physiol 1997 113:1437-1445 ↑ Jez JM, Bowman ME, Dixon RA, Noel JP: Structure and mechanism of chalcone isomerase: an evolutionarily unique enzyme in plants. Nat Struct Biol 2000 7: 786?791 ↑ Herles C, Braune A, Braut M: First bacterial chalcone isomerase isolated from Eubacterium ramulus. Arch Microbiol 2004 181:428-434. ↑ Winkel-Shirley B: Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology and biotechnology. Plant Physiol 2001 126:485-492 ↑ Martin C, Prescott A, Mackay S, Bartlett J, Vrijlandt E: Control of anthocyanin biosyntehsis in flowers Antirrhinum majus. Plant J 1991 1:37-49 ↑ Holton TA, Cornish EC: Genetics and biochemistry of anthocyanin biosynthesis. Plant Cell 1993 7:1071-1083 ↑ Baker ME, Blasco RE: Expansion of the mammalian 3bhydroxysteroid dehydrogenase/plant dihydroflavonol reductase superfamily to include a bacterial cholesterol dehydrogenase, a bacterial UDP-galactose 4-epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus. FEBS Lett 1992 301: 89?93 ↑ Brugliera F, Barri-Rewell G, Holton TA, Mason JG: Isolation and characterization of a flavonoid 3-hydroxylase. cDNA clone corresponding to the Ht1 locus of Petunia hybrida. Plant J 1999 19: 441?451 ↑ Holton TA, Brugliera F, Lester DR, Tanaka Y, Hyland CD, Menting JGT, Lu CY, Farcy E, Stevenson TW, Cornish EC: Cloning and expression of cytochrome P450 genes controlling flower colour. Nature 1993 366:276?279 ↑ de Vetten N, ter Horst J, van Schaik H-P, de Boer A, Mol J, Koes R: A cytochrome b5 is required for full activity of flavonoid 39,59-hydroxylase, a cytochrome P450 involved in the formation of blue flowers. Proc Natl Acad Sci USA 1999 96: 778?783 ↑ Brugliera F, Tull D, Holton TA, Karan M, Treloar N, Simpson K, Skurczynska J, Mason JG: Introduction of a cytochrome b5 enhances the activity of flavonoid 3'5' hydroxylase (a cytochrome P450) in transgenic carnation. Sixth International Congress of Plant Molecular Biology. University of Laval, Quebec, 2000 pp S6?S8 ↑ Marrs KA, Alfenito MR, Lloyd AM, Walbot V: A glutathione S-transferase involved in vacuolar transfer encoded by the maise gene Bronze-2. Nature 1995 375: 397?400 ↑ Alfenito MR, Souer E, Goodman CD, Buell R, Mol J, Koes R, Walbot V: Functional complementation of anthocyanin sequestration in the vacuole by widely divergent glutathione S-transferases. Plant Cell 1998 10: 1135?1149

Bioactivity

Tea Related

• Tea category 茶の種類
• Tea consumption 茶の消費量
• Tea and health　茶と健康

General Flavonoid

All flavonoids

photoprotectant, anti-oxidant
Not only anthocyanins but even simple structures such as chalcone can absorb UV wavelengths strongly. The ability of photoprotection is derived from its anti-oxidative activity. For example, quercetin is a more effective photoprotectant and anti-oxidant than kaempferol. ^{[1] [2]}

1. ↑ Ryan KG, Swinny EE, Markham KR, Winefield C (2002) "Flavonoid gene expression and UV photoprotection in transgenic and mutant Penunia leaves" Phytochem 59:23-32 PMID 11754940
2. ↑ Li J, Ou-Lee T-M, Raba R, Amundson RG, Last RL (1993) "Arabidopsis flavonoid mutants are hypersensitive to UV-B irradiation" Plant Cell 5: 171-179 PMID 12271060

• [Doc:Antioxidant|Details of antioxidant activity]

Flavanols
Quercetin in onions and flavanols in cocoa are said to reduce blood pressure in hypertensive animals ^[1], but their effect or mechanism is not clinically conclusive.

1. ↑ Hooper L, Kroon PA, Rimm EB, et al. (2008) "Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials" Am J Clin Nutr 88:38–50 PMID 18614722

Tannins (proanthocyanidins) anti-bacteria, anti-fungi

Bioavailability

Flavonoid	Dose	Observation
catechin[1]	5.8 g	26% was excreted within 24h. m-hydroxyphenyl propionic acid was detected in plasma after 6h
3-O-methyl-catechin[2]	2 g	plasma level 11-18 ug/ml within 2h; 38% was excreted as glucuronides and sulphates in urine within 120h
quercetin[3]	64 mg (as fried onion)	plasma level 1 uM, 2h later
quercetin[4]	4 g (as supplement)	undetected in urine or plasma
decaffeinated green tea[5]	88 mg EGCG, 82 mg EGC, 33 mg ECG, and 32 mg EC	plasma level 46-268 ng/ml, 82-206 ng/ml, undetected, and 40-80 ng/ml, respectively.

Isoflavones

Isoflavones are efficiently absorbed from the colon and exhibit the highest bioavailability. (Usually polyphenols absorbed from the colon show very low availability.) Daidzein and genistein are known to form chlorinated products (e.g. 3- and 8-chlorodaidzein), then are conjugated with glucuronides and excreted in bile.

Anthocyanins

Although anthocyanins comprise ca. 50% of total polyphenols, they are poorly available (less than 1% of intake in urinary levels). Anthocyanins are absorbed from the stomach, and their glycosides appear in plasma soon after the intake. In blood, only anthocyanins exist in a non-conjugated form.

Flavan

Flavan 3-ols and phenolic acids are efficiently abosrbed from the small instestine, a few hours after intake.

Others

Non-absorbed flavonoids are transported to the colon, and subjected to metabolism by microbiota. These flavonoids are therefore absorbed much less compared to flavan 3-ols and phenolic acids. Esterification of phenolic acids (e.g. chlorogenic acid), however, reduces absorption.

During absorption, polyphenols are metabolized to form β-glucuronide and sulfate conjugates (phase II conjugation in the intestinal wall), and catechol units are methylated. C-glycosides such as puerarin remain stable and not conjugated. These metabolized forms show markedly different bioactivities from their aglycones.

1. ↑ Das NP (1971) Biochem Pharmacol 20, 3435-3445
2. ↑ Hackett AM, Griffiths LA, Wermeille M (1985) Xenobiotica 15, 907-914
3. ↑ Hollman PCH et al (1995) Am J Clin Nutr 62, 1276-1282; Hollman PCH et al (1996) Free Rad Biol Med 21, 703-707
4. ↑ Gugler R, Leshik M, Dengler HV (1975) Eur J Clin Pharmacol 9, 229-234
5. ↑ Lee MT et al (1995) Cancer Epidemiol Biomarkers Prev 41,393-399

Representative Names

Database statistics/ranking

This database collects original references that report identification of flavonoid in various plant species. The database consists of three major namespaces: (flavonoid) compounds, plant species, and references. Currently, 6961 flavonoid structures, 3961 plant species, and 5215 references describing total 19861 metabolite-species relationships are registered.

class	FL1 (chalcones)	FL2 (flavanones)	FL3 (flavones)	FL4 (dihydroflavonols)	FL5 (flavonols)	FL6 (flavans)	FL7 (anthocyanidins)	FLI (isoflavonoids)	FLN (neoflavonoids)	Total
#data	690	705	1479	272	1943	291	574	916	96	6961

Flavonoid content in food

The daily intake of polyphenols from plant foods is considered about 1000 mg/day.

Category	Flavonol	Flavone	Flavan	Flavanone
Names	quercetin, kampferol, myricetin, isorhamnetin	apigenin, luteolin	catechin, epicatechin
broccoli ブロッコリ	Δ
celery セロリ		ΔΔ
fava そら豆			ΔΔ
hot pepper とうがらし		ΔΔ
onion たまねぎ	ΔΔ (Δ)
parsley パセリ		ΔΔΔ
peppermint ペパーミント		ΔΔ
spinach ほうれん草		Δ
thyme タイム		ΔΔΔ
watercress クレソン		Δ
dill, fennel ディル, フェンネル		ΔΔΔ

Δ 5 to <10 mg/100 g; ΔΔ 10 to <50 mg/100 g; ΔΔΔ 50< mg/100 g

The following vegetables and herbs have flavonoid contents less than 5 mg/100 g: beets, kidney beans, snap beans, cabbage, carrot, cauliflower, cucumber, endive, gourd, leek, lettuce, green peas, sweet pepper, potato, radish, tomato, oregano, perrilla, rosemary

Design of Flavonoid ID numbers

12-DIGIT

F

L

x

x

y

y

z

z

w

c

c

c

x ... backbone structure (母核構造) 

FL1 aurone and chalcone; FL2 flavanone; FL3 flavone; FL4 Dihydroflavonol; FL5 Flavonol; FL6 Flavan; FL7 Anthocyanin; FLI Isoflavonoid; FLN Neoflavonoid

y ... hydroxylation pattern in A and B ring (水酸基パターン) 

Click above categories to see details. General description is here.

z ... glycosylation pattern (糖修飾パターン) 

Click above categories to see details. General description is here.

w ... halogenation etc. (ハロゲン等) 

Currently unused.

c ... serial number (通し番号)

For Users of Flavonoid Viewer

The flavonoid IDs used in this site is the same as those in Flavonoid Viewer in metabolome.jp except for the following FL7 category.

Anthocyanin glycosylated with other than glucose and galactose
Flavonoid Viewer FL7A..GS	→	This site FL7A..GO