Flavan-3-ol explained

Flavan-3-ol should not be confused with Flavonol.

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.[1]

Chemical structure

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).[2]

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 absence of ketone(s). Catechin monomers, dimers, and trimers (oligomers) are colorless. Higher order polymers, anthocyanidins, exhibit deepening reds and become tannins.

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.[3]

Biosynthesis of (–)-epicatechin

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 enzyme do not use ACPSs, but instead employ coenzyme A esters and have a single active site to perform the necessary series of reactions, e.g. 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.[4] [5] Fluorescence-lifetime imaging microscopy (FLIM) can be used to detect flavanols in plant cells.[6]

Figure 1:Schematic overview of the flavan-3-ol (–)-epicatechin biosynthesis in plants: Enzymes are indicated in blue, abbreviated as follows: E1, phenylalanine ammonia lyase (PAL), E2, tyrosine ammonia lyase (TAL), E3, cinnamate 4-hydroxylase, E4,, E5, chalcone synthase (naringenin-chalcone synthase), E6, chalcone isomerase, E7, Flavonoid 3'-hydroxylase, E8, flavonone 3-hydroxylase, E9, dihydroflavanol 4-reductase, E10, anthocyanidin synthase (leucoanthocyanidin dioxygenase), E11, anthocyanidin reductase. HSCoA, Coenzyme A. L-Tyr, L-tyrosine, L-Phe, L-phenylalanine.

Aglycones

Flavan-3-ols! Image!!Name!!Formula!!Oligomers
Catechin, C, (+)-Catechin C15H14O6 Procyanidins
Epicatechin, EC, (–)-Epicatechin (cis) C15H14O6 Procyanidins
Epigallocatechin, EGC C15H14O7 Prodelphinidins
Epicatechin gallate, ECG C22H18O10
Epigallocatechin gallate, EGCG,
(–)-Epigallocatechin gallate 		C22H18O11
C15H14O5
C15H14O5
C15H14O4 Proguibourtinidins
C15H14O6
C15H14O6 Prorobinetinidins

Dietary sources

See also: Polyphenols in tea and Polyphenols in wine. 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.[7] [8] Flavan-3-ols are also present in the human diet in fruits, in particular pome fruits, berries, vegetables, and wine.[9] Their content in food is variable and affected by various factors, such as cultivar, processing, and preparation.[10]

Bioavailability and metabolism

The bioavailability of flavan-3-ols depends on the food matrix, type of compound and their stereochemical configuration.[11] While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed.[12] 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,[13] mainly by O-methylation and glucuronidation,[14] 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.[15] Only flavan-3-ols with an intact (epi)catechin moiety can be metabolized into 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones (image in Gallery).

Possible adverse effects

As catechins in green tea extract can be hepatotoxic, Health Canada and EFSA have advised for caution,[16] recommending intake should not exceed 800 mg per day.[17]

Research

Research has shown that flavan-3-ols may affect vascular function, blood pressure, and blood lipids, with only minor effects demonstrated, as of 2019.[18] [19] 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".[20] [21] 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.[22]

Notes and References

  1. Ullah C, Unsicker SB, Fellenberg C, Constabel CP, Schmidt A, Gershenzon J, Hammerbacher A . Flavan-3-ols Are an Effective Chemical Defense against Rust Infection . Plant Physiology . 175 . 4 . 1560–1578 . December 2017 . 29070515 . 5717727 . 10.1104/pp.17.00842 .
  2. Book: OPC in Practice . Schwitters B, Masquelier J . 1995 . 3rd . 45289285.
  3. Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A . Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases . Antioxidants & Redox Signaling . 18 . 14 . 1818–1892 . May 2013 . 22794138 . 3619154 . 10.1089/ars.2012.4581 .
  4. Book: Dewick PM . Medicinal Natural Products: a biosynthetic approach. . John Wiley & Sons . 2009 . 168 . 978-0-471-49641-0 .
  5. Winkel-Shirley B . Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology . Plant Physiology . 126 . 2 . 485–493 . June 2001 . 11402179 . 1540115 . 10.1104/pp.126.2.485 .
  6. Mueller-Harvey I, Feucht W, Polster J, Trnková L, Burgos P, Parker AW, Botchway SW . Two-photon excitation with pico-second fluorescence lifetime imaging to detect nuclear association of flavanols . Analytica Chimica Acta . 719 . 68–75 . March 2012 . 22340533 . 10.1016/j.aca.2011.12.068 . 24094780 .
  7. Hammerstone JF, Lazarus SA, Schmitz HH . Procyanidin content and variation in some commonly consumed foods . The Journal of Nutrition . 130 . 8S Suppl . 2086S–2092S . August 2000 . 10917927 . 10.1093/jn/130.8.2086S . free .
  8. Payne MJ, Hurst WJ, Miller KB, Rank C, Stuart DA . Impact of fermentation, drying, roasting, and Dutch processing on epicatechin and catechin content of cacao beans and cocoa ingredients . Journal of Agricultural and Food Chemistry . 58 . 19 . 10518–10527 . October 2010 . 20843086 . 10.1021/jf102391q .
  9. Book: Mabrym H, Harborne JB, Mabry TJ . The Flavonoids . Chapman and Hall . London . 1975 . 978-0-412-11960-6 .
  10. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L . Polyphenols: food sources and bioavailability . The American Journal of Clinical Nutrition . 79 . 5 . 727–747 . May 2004 . 15113710 . 10.1093/ajcn/79.5.727 . free .
  11. Del Río D, Rodríguez Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A . Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases . Antioxidants & Redox Signaling . 18 . 14 . 1818–1892 . May 2013 . 22794138 . 10.1089/ars.2012.4581 . 3619154 .
  12. Rodríguez Mateos A, Weber T, Skene SS, Ottaviani JI, Crozier A, Kelm M, Schroeter H, Heiss C . 6 . Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial . The American Journal of Clinical Nutrition . 108 . 6 . 1229–1237 . December 2018 . 30358831 . 6290365 . 10.1093/ajcn/nqy229 .
  13. Actis-Goretta L, Lévèques A, Rein M, Teml A, Schäfer C, Hofmann U, Li H, Schwab M, Eichelbaum M, Williamson G . 6 . Intestinal absorption, metabolism, and excretion of (−)-epicatechin in healthy humans assessed by using an intestinal perfusion technique . The American Journal of Clinical Nutrition . 98 . 4 . 924–933 . October 2013 . 23864538 . 10.3945/ajcn.113.065789 . free .
  14. Kuhnle G, Spencer JP, Schroeter H, Shenoy B, Debnam ES, Srai SK, Rice-Evans C, Hahn U . 6 . Epicatechin and catechin are O-methylated and glucuronidated in the small intestine . Biochemical and Biophysical Research Communications . 277 . 2 . 507–512 . October 2000 . 11032751 . 10.1006/bbrc.2000.3701 .
  15. Das NP . Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man . Biochemical Pharmacology . 20 . 12 . 3435–3445 . December 1971 . 5132890 . 10.1016/0006-2952(71)90449-7 .
  16. Web site: Health Canada . Summary Safety Review - Green tea extract-containing natural health products - Assessing the potential risk of liver injury (hepatotoxicity) . 2022-05-06 . Health Canada, Government of Canada. 12 December 2017.
  17. Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, Frutos MJ, Galtier P, Gott D, Gundert-Remy U, Lambré C, Leblanc JC, Lillegaard IT, Moldeus P, Mortensen A, Oskarsson A, Stankovic I, Waalkens-Berendsen I, Woutersen RA, Andrade RJ, Fortes C, Mosesso P, Restani P, Arcella D, Pizzo F, Smeraldi C, Wright M . 6 . Scientific opinion on the safety of green tea catechins . EFSA Journal . 16 . 4 . e05239 . April 2018 . 32625874 . 7009618 . 10.2903/j.efsa.2018.5239 .
  18. Ried K, Fakler P, Stocks NP . Effect of cocoa on blood pressure . The Cochrane Database of Systematic Reviews . 4 . 5 . CD008893 . April 2017 . 28439881 . 6478304 . 10.1002/14651858.CD008893.pub3 . Cochrane Hypertension Group .
  19. Raman G, Avendano EE, Chen S, Wang J, Matson J, Gayer B, Novotny JA, Cassidy A . 6 . Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies . The American Journal of Clinical Nutrition . 110 . 5 . 1067–1078 . November 2019 . 31504087 . 6821550 . 10.1093/ajcn/nqz178 .
  20. Web site: Article 13 (5): Cocoa flavanols; Search filters: Claim status - authorised; search - flavanols . European Commission, EU Register . 8 September 2022 . 31 March 2015.
  21. Scientific Opinion on the modification of the authorisation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/20061 following a request in accordance with Article 19 of Regulation (EC) No 1924/2006. EFSA Journal. 12. 5. 2014. 10.2903/j.efsa.2014.3654. free.
  22. Crowe-White . Kristi M . Evans . Levi W . Kuhnle . Gunter G C . Milenkovic . Dragan . Stote . Kim . Wallace . Taylor . Handu . Deepa . Senkus . Katelyn E . Flavan-3-ols and cardiometabolic health: First ever dietary bioactive guideline . Advances in Nutrition . 3 October 2022 . 13 . 6 . 2070–83 . 10.1093/advances/nmac105. 36190328 . 9776652 . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Flavan-3-ol".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.