Flavan-3-ol
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Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compounds, such as catechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, proanthocyanidins, theaflavins, thearubigins. They play a part in plant defense and are present in the majority of plants.<ref>Template:Cite journal</ref>
Chemical structureEdit
The single-molecule (monomer) catechin, or isomer epicatechin (see diagram), adds four hydroxyls to flavan-3-ol, making building blocks for concatenated polymers (proanthocyanidins) and higher order polymers (anthocyanidins).<ref name="ReferenceA">Template:Cite book</ref>
Flavan-3-ols possess two chiral carbons, meaning four diastereoisomers occur for each of them. They are distinguished from the yellow, ketone-containing flavonoids such as quercitin and rutin, which are called flavonols. Early use of the term bioflavonoid was imprecisely applied to include the flavanols, which are distinguished by the absence of ketonse. Catechin monomers, dimers, and trimers (oligomers) are colorless. Higher order polymers, anthocyanidins, exhibit deepening reds and become tannins.<ref name="ReferenceA" />
Catechin and epicatechin are epimers, with (–)-epicatechin and (+)-catechin being the most common optical isomers found in nature. Catechin was first isolated from the plant extract catechu, from which it derives its name. Heating catechin past its point of decomposition releases pyrocatechol (also called catechol), which explains the common origin of the names of these compounds.
Epigallocatechin and gallocatechin contain an additional phenolic hydroxyl group when compared to epicatechin and catechin, respectively, similar to the difference in pyrogallol compared to pyrocatechol.
Catechin gallates are gallic acid esters of the catechins; an example is epigallocatechin gallate, which is commonly the most abundant catechin in tea. Proanthocyanidins and thearubigins are oligomeric flavan-3-ols.
In contrast to many other flavonoids, flavan-3-ols do not generally exist as glycosides in plants.<ref name=":1"/>
Biosynthesis of (–)-epicatechinEdit
The flavonoids are products from a cinnamoyl-CoA starter unit, with chain extension using three molecules of malonyl-CoA. Reactions are catalyzed by a type III PKS enzyme. These enzymes do not use ACPSs, but instead employ coenzyme A esters and have a single active site to perform the necessary series of reactions: chain extension, condensation, and cyclization. Chain extension of 4-hydroxycinnamoyl-CoA with three molecules of malonyl-CoA gives initially a polyketide (Figure 1), which can be folded. These allow Claisen-like reactions to occur, generating aromatic rings.<ref name="Dewick2009p168">Template:Cite book</ref><ref name="Winkel-Shirley2001p485-493">Template:Cite journal</ref> Fluorescence-lifetime imaging microscopy (FLIM) can be used to detect flavanols in plant cells.<ref>Template:Cite journal</ref>
- Figure 1: Schematic overview of the flavan-3-ol (–)-epicatechin biosynthesis from tyrosine (Tyr) or phenylalanine (Phe) in plants. Enzymes are indicated in blue, abbreviated as follows:
AglyconesEdit
| Image | Name | Formula | Oligomers |
|---|---|---|---|
| (+)-Catechin | Catechin, C, (+)-Catechin | C15H14O6 | Procyanidins |
| Epicatechin | Epicatechin, EC, (–)-Epicatechin (cis) | C15H14O6 | Procyanidins |
| Epigallocatechin | Epigallocatechin, EGC | C15H14O7 | Prodelphinidins |
| Epicatechin gallate | Epicatechin gallate, ECG | C22H18O10 | |
| Epigallocatechin gallate | Epigallocatechin gallate, EGCG, (–)-Epigallocatechin gallate |
C22H18O11 | |
| Epiafzelechin | Epiafzelechin | C15H14O5 | |
| Fisetinidol | Fisetinidol | C15H14O5 | |
| Guibourtinidol | Guibourtinidol | C15H14O4 | Proguibourtinidins |
| Mesquitol | Mesquitol | C15H14O6 | |
| Robinetinidol | Robinetinidol | C15H14O6 | Prorobinetinidins |
-Catechin.svg){kind=link}
-Epicatechin.svg){kind=link}
Dietary sourcesEdit
Flavan-3-ols are abundant in teas derived from the tea plant Camellia sinensis, as well as in some cocoas (made from the seeds of Theobroma cacao), although the content is affected considerably by processing, especially in chocolate.<ref name="Hammerstone_2000">Template:Cite journal</ref><ref name="Payne_2010">Template:Cite journal</ref> Flavan-3-ols are also present in the human diet in fruits, in particular pome fruits, berries, vegetables, and wine.<ref>Template:Cite book</ref> Their content in food is variable and affected by various factors, such as cultivar, processing, and preparation.<ref name=":2">Template:Cite journal</ref>
Bioavailability and metabolismEdit
The bioavailability of flavan-3-ols depends on the food matrix, type of compound and their stereochemical configuration.<ref name=":1">Template:Cite journal</ref> While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed.<ref name=":1" /><ref>Template:Cite journal</ref> Most data for human metabolism of flavan-3-ols are available for monomeric compounds, especially epiatechin. These compounds are taken up and metabolized upon uptake in the jejunum,<ref>Template:Cite journal</ref> mainly by O-methylation and glucuronidation,<ref>Template:Cite journal</ref> and then further metabolized by the liver. The colonic microbiome has also an important role in the metabolism of flavan-3-ols and they are catabolized to smaller compounds such as 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones and hippuric acid.<ref>Template:Cite journal</ref><ref name=":0" /> Only flavan-3-ols with an intact (epi)catechin moiety can be metabolized into 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones (image in Gallery).<ref name="Ottaviani 9859"/>
Possible adverse effectsEdit
As catechins in green tea extract can be hepatotoxic, Health Canada and EFSA have advised for caution,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> recommending intake should not exceed 800 mg per day.<ref>Template:Cite journal</ref>
ResearchEdit
Template:See also Research has shown that flavan-3-ols may affect vascular function, blood pressure, and blood lipids, with only minor effects demonstrated, as of 2019.<ref>Template:Cite journal</ref><ref name="raman">Template:Cite journal</ref> In 2015, the European Commission approved a health claim for cocoa solids containing 200 mg of flavanols, stating that such intake "may contribute to maintenance of vascular elasticity and normal blood flow".<ref name="EC-cocoa">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="efsa2014">Template:Cite journal</ref> As of 2022, food-based evidence indicates that intake of 400–600 mg per day of flavan-3-ols could have a small positive effect on cardiovascular biomarkers.<ref>Template:Cite journal</ref>
GalleryEdit
- Schematic representation of (−)-epicatechin metabolism in humans as a function of time post-oral intake.jpg
Schematic representation of the flavan-3-ol (−)-epicatechin metabolism in humans as a function of time post-oral intake. SREM: structurally related (−)-epicatechin metabolites. 5C-RFM: 5-carbon ring fission metabolites. 3/1C-RFM: 3- and 1-carbon-side chain ring fission metabolites. The structures of the most abundant (−)-epicatechin metabolites present in the systemic circulation and in urine are depicted.<ref name=":0">Template:Cite journal</ref>
- Flavan-3-ol precursors of the microbial metabolite 5-(3′-4′-dihydroxyphenyl)-γ-valerolactone.jpg
Flavan-3-ol precursors of the microbial metabolite 5-(3′/4′-dihydroxyphenyl)-γ-valerolactone (γVL). Only compounds with intact (epi)catechin moiety result in the formation of γVL by the intestinal microbiome. ECG, (−)-epicatechin-3-O-gallate; EGCG, Epigallocatechin gallate; EGC, Epigallocatechin.<ref name="Ottaviani 9859">Template:Cite journal</ref>