(+)-catechin
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Catechin is a flavan-3-ol, a type of secondary metabolite providing
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from '' catechu'', which is the tannic juice or boiled extract of ''Mimosa catechu'' (''
Acacia catechu ''Senegalia catechu'' is a deciduous, thorny tree which grows up to in height. The plant is called ''khair''
in H ...
'' L.f).


Chemistry

Catechin possesses two benzene rings (called the A- and B-rings) and a
dihydropyran In organic chemistry, dihydropyran refers to two heterocyclic compounds with the chemical formula, formula C5H8O: *3,4-Dihydropyran, 3,4-Dihydro-2''H''-pyran *3,6-dihydro-2''H''-pyran Nomenclature In IUPAC names, "dihydro" refers to the two adde ...
heterocycle (the C-ring) with a
hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy g ...
on carbon 3. The A-ring is similar to a resorcinol moiety while the B-ring is similar to a catechol moiety. There are two chiral centers on the molecule on carbons 2 and 3. Therefore, it has four diastereoisomers. Two of the isomers are in trans configuration and are called ''catechin'' and the other two are in
cis configuration Cis or cis- may refer to: Places * Cis, Trentino, in Italy * In Poland: ** Cis, Świętokrzyskie Voivodeship, south-central ** Cis, Warmian-Masurian Voivodeship, north Math, science and biology * cis (mathematics) (cis(''θ'')), a trigonome ...
and are called ''epicatechin''. The most common catechin isomer is (+)-catechin. The other stereoisomer is (-)-catechin or ''ent''-catechin. The most common epicatechin isomer is (-)-epicatechin (also known under the names L-epicatechin, epicatechol, (-)-epicatechol, l-acacatechin, l-epicatechol, epi-catechin, 2,3-''cis''-epicatechin or (2''R'',3''R'')-(-)-epicatechin). The different epimers can be separated using
chiral column chromatography Chiral column chromatography is a variant of column chromatography that is employed for the separation of enantiomers, e. g. in racemates. The stationary phase contains a single enantiomer of a chiral compound. The chiral stationary phase can be ...
. Making reference to no particular isomer, the molecule can just be called catechin. Mixtures of the different enantiomers can be called (±)-catechin or DL-catechin and (+/-)-epicatechin or DL-epicatechin. Catechin and epicatechin are the building blocks of the proanthocyanidins, a type of condensed tannin. File:(+)-Catechin.png, (+)-catechin (2''R'',3''S'') File:Catechin.png, (-)-catechin (2''S'',3''R'') File:(–)-Epicatechin.svg, (-)-epicatechin (2''R'',3''R'') File:(+)-epicatechin.svg, (+)-epicatechin (2''S'',3''S'') Moreover, the flexibility of the C-ring allows for two conformation isomers, putting the B-ring either in a pseudoequatorial position (E conformer) or in a pseudoaxial position (A conformer). Studies confirmed that (+)-catechin adopts a mixture of A- and E-conformers in aqueous solution and their conformational equilibrium has been evaluated to be 33:67. As flavonoids, catechins can act as antioxidants when in high concentration ''in vitro'', but compared with other flavonoids, their antioxidant potential is low. The ability to quench singlet oxygen seems to be in relation with the chemical structure of catechin, with the presence of the catechol moiety on ring B and the presence of a hydroxyl group activating the double bond on ring C.


Oxidation

Electrochemical experiments show that (+)-catechin oxidation mechanism proceeds in sequential steps, related with the catechol and resorcinol groups and the oxidation is pH-dependent. The oxidation of the catechol 3',4'-dihydroxyl electron-donating groups occurs first, at very low positive potentials, and is a reversible reaction. The hydroxyl groups of the resorcinol moiety oxidised afterwards were shown to undergo an irreversible oxidation reaction. The
laccase Laccases () are multicopper oxidases found in plants, fungi, and bacteria. Laccases oxidize a variety of phenolic substrates, performing one-electron oxidations, leading to crosslinking. For example, laccases play a role in the formation of lign ...
/
ABTS In biochemistry, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) is a chemical compound used to observe the reaction kinetics of specific enzymes. A common use for it is in the enzyme-linked immunosorbent assay (ELISA) to detect the ...
system oxidizes (+)-catechin to oligomeric products of which
proanthocyanidin A2 Procyanidin A2 is an A type proanthocyanidin. It is found in avocado, chestnut, cranberry juice concentrate, lychee fruit pericarp, peanut The peanut (''Arachis hypogaea''), also known as the groundnut, goober (US), pindar (US) or monke ...
is a dimer.


Spectral data


Natural occurrences

(+)-Catechin and (-)-epicatechin as well as their gallic acid conjugates are ubiquitous constituents of vascular plants, and frequent components of traditional herbal remedies, such as ''
Uncaria rhynchophylla ''Uncaria rhynchophylla'' () or the cat's claw herb is a plant species used in traditional Chinese medicine. (+)-Catechin and (-)-epicatechin are found in the plant as well as the alkaloid rhynchophylline. References External links

* ...
''. The two isomers are mostly found as
cacao Cacao is the seed from which cocoa and chocolate are made, from Spanish cacao, an adaptation of Nahuatl cacaua, the root form of cacahuatl ("bean of the cocoa-tree"). It may also refer to: Plants *''Theobroma cacao'', a tropical evergreen tree ** ...
and tea constituents, as well as in '' Vitis vinifera'' grapes.


In food

The main dietary sources of catechins in Europe and the United States are tea and
pome In botany, a pome is a type of fruit produced by flowering plants in the subtribe Malinae of the family Rosaceae. Well-known pomes include the apple, pear, and quince. Etymology The word ''pome'' entered English in the late 14th century, and re ...
fruits. Catechins and epicatechins are found in
cocoa Cocoa may refer to: Chocolate * Chocolate * ''Theobroma cacao'', the cocoa tree * Cocoa bean, seed of ''Theobroma cacao'' * Chocolate liquor, or cocoa liquor, pure, liquid chocolate extracted from the cocoa bean, including both cocoa butter and ...
, which, according to one database, has the highest content (108 mg/100 g) of catechins among foods analyzed, followed by prune juice (25 mg/100 ml) and broad bean pod (16 mg/100 g). Açaí oil, obtained from the fruit of the açaí palm (''Euterpe oleracea''), contains (+)-catechins (67 mg/kg). Catechins are diverse among foods, from peaches to
green tea Green tea is a type of tea that is made from '' Camellia sinensis'' leaves and buds that have not undergone the same withering and oxidation process which is used to make oolong teas and black teas. Green tea originated in China, and since the ...
and vinegar. Catechins are found in barley grain where they are the main phenolic compound responsible for dough discoloration. The taste associated with monomeric (+)-catechin or (-)-epicatechin is described as slightly astringent, but not bitter.


Metabolism


Biosynthesis

The biosynthesis of catechin begins with ma 4-hydroxycinnamoyl CoA starter unit which undergoes chain extension by the addition of three
malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and commi ...
s through a PKSIII pathway. 4-hydroxycinnamoyl CoA is biosynthesized from L-phenylalanine through the Shikimate pathway. L-phenylalanine is first deaminated by phenylalanine ammonia lyase (PAL) forming cinnamic acid which is then oxidized to 4-hydroxycinnamic acid by cinnamate 4-hydroxylase. Chalcone synthase then catalyzes the condensation of 4-hydroxycinnamoyl CoA and three molecules of malonyl-CoA to form
chalcone Chalcone is the organic compound C6H5C(O)CH=CHC6H5. It is an α,β-unsaturated ketone. A variety of important biological compounds are known collectively as chalcones or chalconoids. Chemical properties Chalcones have two absorption maxima a ...
. Chalcone is then isomerized to naringenin by chalcone isomerase which is oxidized to
eriodictyol Eriodictyol is a bitter-masking flavanone, a flavonoid extracted from yerba santa (''Eriodictyon californicum''), a plant native to North America. Eriodictyol is one of the four flavanones identified in this plant as having taste-modifying proper ...
by flavonoid 3'- hydroxylase and further oxidized to taxifolin by flavanone 3-hydroxylase. Taxifolin is then reduced by dihydroflavanol 4-reductase and
leucoanthocyanidin reductase In enzymology, a leucoanthocyanidin reductase () (LAR, aka leucocyanidin reductase or LCR) is an enzyme that catalyzes the chemical reaction :(2R,3S)-catechin + NADP+ + H2O \rightleftharpoons 2,3-trans-3,4-cis-leucocyanidin + NADPH + H+ The 3 ...
to yield catechin. The biosynthesis of catechin is shown below Leucocyanidin reductase (LCR) uses 2,3-trans-3,4-cis-
leucocyanidin Leucocyanidin is a colorless chemical compound that is a member of the class of natural products known as leucoanthocyanidins. Chemistry (+)-Leucocyanidin can be synthesized from (+)-dihydroquercetin by reduction with sodium borohydride. Mola ...
to produce (+)-catechin and is the first enzyme in the proanthocyanidins (PA)-specific pathway. Its activity has been measured in leaves, flowers, and seeds of the legumes '' Medicago sativa'', ''
Lotus japonicus ''Lotus japonicus'' is a wild legume that belongs to family Fabaceae. Members of this family are very diverse, constituting about 20,000 species. They are of significant agricultural and biological importance as many of the legume species are ri ...
'', ''
Lotus uliginosus ''Lotus pedunculatus'' (formerly ''Lotus uliginosus''), the big trefoil, greater bird's-foot-trefoil or marsh bird's-foot trefoil, is a member of the pea family (Fabaceae). It is a herbaceous perennial growing throughout Europe in damp, open loc ...
'', '' Hedysarum sulfurescens'', and '' Robinia pseudoacacia''. The enzyme is also present in '' Vitis vinifera'' (grape).


Biodegradation

Catechin oxygenase, a key enzyme in the degradation of catechin, is present in fungi and bacteria. Among bacteria, degradation of (+)-catechin can be achieved by '' Acinetobacter calcoaceticus''. Catechin is metabolized to
protocatechuic acid Protocatechuic acid (PCA) is a dihydroxybenzoic acid, a type of phenolic acid. It is a major metabolite of antioxidant polyphenols found in green tea. It has mixed effects on normal and cancer cells in ''in vitro'' and ''in vivo'' studies. Biolo ...
(PCA) and
phloroglucinol carboxylic acid Phloroglucinol carboxylic acid is a trihydroxybenzoic acid, a type of phenolic acid. It is produced by ''Pseudomonas fluorescens''. It is a catechin degradation product excreted by the bacterium ''Acinetobacter calcoaceticus'', a species of bacte ...
(PGCA). It is also degraded by '' Bradyrhizobium japonicum''. Phloroglucinol carboxylic acid is further
decarboxylated Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...
to phloroglucinol, which is dehydroxylated to resorcinol. Resorcinol is hydroxylated to hydroxyquinol. Protocatechuic acid and hydroxyquinol undergo intradiol cleavage through
protocatechuate 3,4-dioxygenase In enzymology, a protocatechuate 3,4-dioxygenase () is an enzyme that catalyzes the chemical reaction : 3,4-dihydroxybenzoate + O2 \rightleftharpoons 3-carboxy-cis,cis-muconate Thus, the two substrates of this enzyme are 3,4-dihydroxybenzoate ( ...
and
hydroxyquinol 1,2-dioxygenase In enzymology, a hydroxyquinol 1,2-dioxygenase () is an enzyme that catalyzes the chemical reaction :benzene-1,2,4-triol + O2 \rightleftharpoons 3-hydroxy-cis,cis-muconate Thus, the two substrates of this enzyme are benzene-1,2,4-triol (hydro ...
to form
β-carboxy cis, cis-muconic acid 3-Carboxy-''cis'',''cis''-muconic acid is a metabolite of the catechin degradation by '' Bradyrhizobium japonicum''. The enzyme 3-carboxy-''cis'',''cis''-muconate cycloisomerase uses 2-carboxy-2,5-dihydro-5-oxofuran-2-acetate to produce 3-carb ...
and maleyl acetate. Among fungi, degradation of catechin can be achieved by ''
Chaetomium cupreum ''Chaetomium cupreum'' is a fungus in the family Chaetomiaceae. It is able to decay in manufactured cellulosic materials, and is known to antagonize a wide range of soil microorganisms. This species is component of the biocontrol agent, Ketomium ...
''.


Metabolism in humans

Catechins are metabolised upon uptake from the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
, in particular the jejunum, and in the liver, resulting in so-called structurally-related epicatechin metabolites (SREM). The main metabolic pathways for SREMs are glucuronidation, sulfation and
methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
of the catechol group by catechol-O-methyl transferase, with only small amounts detected in plasma. The majority of dietary catechins are however metabolised by the colonic microbiome to gamma-valerolactones and
hippuric acid Hippuric acid ( Gr. ''hippos'', horse, ''ouron'', urine) is a carboxylic acid and organic compound. It is found in urine and is formed from the combination of benzoic acid and glycine. Levels of hippuric acid rise with the consumption of phenoli ...
s which undergo further biotransformation, glucuronidation, sulfation and
methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
in the liver. The stereochemical configuration of catechins has a strong impact on their uptake and metabolism as uptake is highest for (-)-epicatechin and lowest for (-)-catechin.


Biotransformation

Biotransformation of (+)-catechin into taxifolin by a two-step oxidation can be achieved by '' Burkholderia'' sp. (+)-Catechin and (-)-epicatechin are transformed by the endophytic filamentous fungus '' Diaporthe'' sp. into the 3,4-cis-dihydroxyflavan derivatives, (+)-
(2R,3S,4S)-3,4,5,7,3',4'-hexahydroxyflavan Leucocyanidin is a colorless chemical compound that is a member of the class of Natural product, natural products known as leucoanthocyanidins. Chemistry (+)-Leucocyanidin can be synthesized from (+)-dihydroquercetin by reduction with sodium b ...
(leucocyanidin) and (-)-(2R,3R,4R)-3,4,5,7,3',4'-hexahydroxyflavan, respectively, whereas (-)-catechin and (+)-epicatechin with a 2S-phenyl group resisted the biooxidation.
Leucoanthocyanidin reductase In enzymology, a leucoanthocyanidin reductase () (LAR, aka leucocyanidin reductase or LCR) is an enzyme that catalyzes the chemical reaction :(2R,3S)-catechin + NADP+ + H2O \rightleftharpoons 2,3-trans-3,4-cis-leucocyanidin + NADPH + H+ The 3 ...
(LAR) uses (2''R'',3''S'')-catechin, NADP+ and H2O to produce 2,3-trans-3,4-cis-
leucocyanidin Leucocyanidin is a colorless chemical compound that is a member of the class of natural products known as leucoanthocyanidins. Chemistry (+)-Leucocyanidin can be synthesized from (+)-dihydroquercetin by reduction with sodium borohydride. Mola ...
, NADPH, and H+. Its gene expression has been studied in developing grape berries and grapevine leaves.


Glycosides

* (2R,3S)-Catechin-7-O-β-D-glucopyranoside can be isolated from barley (''Hordeum vulgare'' L.) and malt. * Epigeoside (Catechin-3-O-alpha-L-rhamnopyranosyl-(1-4)-beta-D-glucopyranosyl-(1–6)-beta-D-glucopyranoside) can be isolated from the rhizomes of ''
Epigynum auritum ''Epigynum auritum'' is a plant species in the genus '' Epigynum''. It is native to Yunnan Province in China, as well as Assam State in India, Laos, Thailand, Myanmar (Burma), and the Peninsular region of Malaysia Malaysia ( ; ) is a co ...
''.


Research


Vascular function

Only limited evidence from dietary studies indicates that catechins may affect endothelium-dependent vasodilation which could contribute to normal blood flow regulation in humans. Green tea catechins may improve blood pressure, especially when systolic blood pressure is above 130 mmHg. Due to extensive metabolism during digestion, the fate and activity of catechin metabolites responsible for this effect on blood vessels, as well as the actual mode of action, are unknown.


Adverse events

Catechin and its metabolites can bind tightly to red blood cells and thereby induce the development of
autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...
, resulting in haemolytic anaemia and renal failure. This resulted in the withdrawal of the catechin-containing drug Catergen, used to treat viral hepatitis, from market in 1985. Catechins from
green tea Green tea is a type of tea that is made from '' Camellia sinensis'' leaves and buds that have not undergone the same withering and oxidation process which is used to make oolong teas and black teas. Green tea originated in China, and since the ...
can be
hepatotoxic Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...
and the European Food Safety Authority has recommended not to exceed 800 mg/d.


Other

One limited meta-analysis showed that increasing consumption of green tea and its catechins to seven cups per day provided a small reduction in
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
. Nanoparticle methods are under preliminary research as potential delivery systems of catechins.


Botanical effects

Catechins released into the ground by some plants may hinder the growth of their neighbors, a form of
allelopathy Allelopathy is a biological phenomenon by which an organism produces one or more biochemicals that influence the germination, growth, survival, and reproduction of other organisms. These biochemicals are known as allelochemicals and can have be ...
. '' Centaurea maculosa'', the spotted knapweed often studied for this behavior, releases catechin isomers into the ground through its roots, potentially having effects as an
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
or
herbicide Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...
. One hypothesis is that it causes a reactive oxygen species wave through the target plant's root to kill root cells by
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
. Most plants in the European ecosystem have defenses against catechin, but few plants are protected against it in the North American ecosystem where '' Centaurea maculosa'' is an invasive, uncontrolled weed. Catechin acts as an infection-inhibiting factor in strawberry leaves. Epicatechin and catechin may prevent coffee berry disease by inhibiting appressorial melanization of ''
Colletotrichum kahawae ''Colletotrichum kahawae'' is a fungal plant pathogen that causes coffee berry disease (CBD) on ''Coffea arabica'' crops. The pathogen is an ascomycete that reproduces asexually. The asexual spores (conidia) are stored within acervuli. This dis ...
''.


References


External links

* {{Flavanol Flavanols Catechols Nutrition