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.[2]
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.
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]
The
bioavailability of flavan-3-ols depends on the
food matrix, type of compound and their
stereochemical configuration.[12] While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed.[12][13] 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,[14] mainly by O-methylation and glucuronidation,[15] 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.[16][17] Only flavan-3-ols with an intact (epi)catechin moiety can be metabolized into 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones (image in Gallery).[18]
Research has shown that flavan-3-ols may affect
vascular function,
blood pressure, and
blood lipids, with only minor effects demonstrated, as of 2019.[21][22] 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".[23][24] 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.[25]
Gallery
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.[17]
Flavan-3-ol precursors of the microbial metabolite 5-(3′/4′-dihydroxyphenyl)-γ-valerolactone (gVL). 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.[18]
^Payne MJ, Hurst WJ, Miller KB, Rank C, Stuart DA (October 2010). "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.
doi:
10.1021/jf102391q.
PMID20843086.
^Mabrym H, Harborne JB, Mabry TJ (1975). The Flavonoids. London: Chapman and Hall.
ISBN978-0-412-11960-6.
^Kuhnle G, Spencer JP, Schroeter H, Shenoy B, Debnam ES, Srai SK, et al. (October 2000). "Epicatechin and catechin are O-methylated and glucuronidated in the small intestine". Biochemical and Biophysical Research Communications. 277 (2): 507–512.
doi:
10.1006/bbrc.2000.3701.
PMID11032751.
^Das NP (December 1971). "Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man". Biochemical Pharmacology. 20 (12): 3435–3445.
doi:
10.1016/0006-2952(71)90449-7.
PMID5132890.