Flavan-3-ol metabolic pathway (WP4238)
Homo sapiens
Proposed metabolic pathway of flavan-3-ols (also known as flavanols) in humans. Flavanols are derivatives of flavans and include catechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, proanthocyanidins, theaflavins, thearubigins. These compounds differ considerably not only in their structural and functional properties, but also in their metabolism and bioavailability. Green arrows indicate microbiota-mediated steps, and red arrows represent mammalian enzyme-mediated conversions. Pink arrows indicate steps that can be both microbiota- or enzyme-mediated. This pathway was developed based upon 22 papers; black arrows indicate missing information regarding the nature of conversion. Acknowledgements: This pathway is based upon work from COST Action POSITIVe, supported by COST (European Cooperation in Science and Technology).
Authors
Eirini Deligiannidou , Egon Willighagen , Denise Slenter , Kristina Hanspers , Lars Willighagen , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
classic metabolic pathwayLabel | Type | Compact URI | Comment |
---|---|---|---|
3-(3,4-dihydroxyphenyl)propanoic acid | Metabolite | pubchem.compound:348454 | C9H10O43-(3,4-dihydroxyphenyl)propanoic acidDihydrocaffeic acid |
Theaflavin | Metabolite | pubchem.compound:114777 | C29H24O12Theaflavin |
1-(3'-4',5-trihydroxyphenyl)-3-(2'',4'',6''-trihydroxy)propan-2-ol | Metabolite | pubchem.compound:21722175 | |
(-)-Epicatechin-3'-O-glucuronide | Metabolite | pubchem.compound:76969982 | |
5-(3''-4''-Dihydroxyphenyl)-gamma-valerolactone | Metabolite | pubchem.compound:89285 | C11H12O45-[(3,4-dihydroxyphenyl)methyl]oxolan-2-one |
Pyrogallol | Metabolite | pubchem.compound:1057 | C6H6O3Benzene-1,2,3-triol |
4-O-Methylgallic acid | Metabolite | pubchem.compound:78016 | |
(-)-Epicatechin | Metabolite | pubchem.compound:72276 | C15H14O6(3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol3,5,7,3',4'-Pentahydroxyflavane |
Theaflavin-3-gallate | Metabolite | pubchem.compound:102115506 | C36H28O16(3R)-5,7-dihydroxy-2-{1,2,8-trihydroxy-9-oxo-4-[3S0-,5,7-trihydroxy-3,4-dihydro-2H-1-benzopyron-2-yl]benzo[7]annuel-6-yl}-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate) |
3-Hydroxyhippuric acid | Metabolite | pubchem.compound:450268 | C9H9NO43-hydroxyhippuric acid3-hydroxyhippuric acid N-(3-hydroxybenzoyl)glucine |
Theaflavin-3'-gallate | Metabolite | pubchem.compound:102115505 | C36H28O16[(2R,3R)-5,7-dihydroxy-2-[3,4,5-trihydroxy-6-oxo-1-[(2S,3S)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-8-yl]-3,4-dihydro-2H-chromen-3-yl]3,4,5-trihydroxybenzoate |
(+)-Catechin | Metabolite | pubchem.compound:1203 | |
3-Hydroxybenzoic acid | Metabolite | pubchem.compound:7420 | C7H6O33-hdroxybenzoic acidm-hydroxybenzoic acid 3-hydroxybenzenecarboxylic acid |
Benzoic acid-4-sulfate | Metabolite | pubchem.compound:18690341 | aka 4-Sulfooxybenzoic acid |
4-[(10R)-3,6-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]valeric acid | Metabolite | chebi:52023 | 5(phenyl)-gamma-hydroxyvaleric acid-3'-sulfate |
Dihydroferulic acid-4'-O-glucuronide | Metabolite | pubchem.compound:190069 | |
3-(4'hydroxyphenyl)-propionic acid 3'-sulfate | Metabolite | inchikey:MIMULQQHBAZGER-UHFFFAOYSA-M | AKA 3-(4'-Hydroxyphenyl)propionic acid-3'-sulfate; foudn in PhytoHub https://phytohub.eu/entries/PHUB001753 |
m-Coumaric acid | Metabolite | pubchem.compound:637541 | C9H8O3m-Coumaric acid3-hydroxycinnamic acid |
5-(3'-hydroxyphenyl)-gamma-valerolactone-4'-O-glucuronide | Metabolite | pubchem.compound:124202062 | |
Dihydroferulic acid-4'-O-sulfate | Metabolite | pubchem.compound:187489 | |
Pyrocatechol | Metabolite | pubchem.compound:289 | C6H6O2Benzene-1,2-diol |
Ferulic acid-4'-O-glucuronide | Metabolite | pubchem.compound:6443140 | C16H18O10(2R,3R,4R,5S,6R)-6-{4-[(1E)-2-carboxyeth-1-en-1-yl]-2-methoxyphenoxy}-3,4,5-trihydroxyoxane-2-carboxylic acidtrans-Ferulic acid glucuronide |
Dihydrocaffeic acid 3-sulfate | Metabolite | pubchem.compound:49844181 | |
(-)Epigallocatechin | Metabolite | pubchem.compound:72277 | C15H14O7(2R,3R)-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol) |
Isoferulic acid-3'-sulfate | Metabolite | pubchem.compound:71749556 | C10H10O7S(2E)-3-[4-methoxy-3-(sulfooxyphenyl]propan-2-enoic acid |
Isoferulic acid-3'-O-glucuronide | Metabolite | pubchem.compound:49844484 | C16H18O10(2S,3S,4S,5R,6S)-6-[5-[(E)-2-carboxyethenyl]-2-methoxyphenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid |
5-(3',4',5'-Trihydroxyphenyl)-gamma-valerolactone | Metabolite | pubchem.compound:44389277 | C11H12O55-[(3,4,5-trihydroxyphenyl)methyl]oxolan-2-one |
5-[(4-hydroxyphenyl)methyl]oxolan-2-one | Metabolite | pubchem.compound:11550142 | C11H12O35-[(4-hydroxyphenyl)methyl]oxolan-2-one5-(4'-hydroxyphenyl)-gamma-valerolactone |
Ferulic acid | Metabolite | pubchem.compound:709 | C10H10O43-(4'-hydroxy-3-methoxyphenyl)prop-2-enoic acid3-methylcaffeic acid |
Caffeic acid | Metabolite | pubchem.compound:689043 | C9H8O4(E )-3-(3,4-dihydroxyphenyl)prop-2-enoic acid |
3-Phenylpropionic acid | Metabolite | pubchem.compound:107 | C9H10O23-phenylpropionic acid3-(phenyl)propionic acid Benzenepropanoic acid Dihydrocinnamic acid |
Benzoic acid | Metabolite | pubchem.compound:243 | C7H6O2benzoic acid |
Homovanillic acid | Metabolite | pubchem.compound:1738 | C9H10O4Homovanillic acid(4-hydroxy-3-methoxyphenyl)acetic acid3-methoxy-4-hydroxyphenylacetic acid 3-methoxy-4-hydroxyphenylacetate 3'-methoxy-4'-hydroxyphenylacetic |
p-hydroxyphenylacetic acid | Metabolite | pubchem.compound:127 | |
Coumaric Acid 4'-O-glucuronide | Metabolite | pubchem.compound:71314996 | |
5'-(4'-hydroxyphenyl)-gamma-valerolactone-3-'sulfate | Metabolite | chebi:88750 | Might be know under the name 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate [PMID:31694297]. |
3,4-Dihydroxybenzoic acid | Metabolite | chebi:36062 | C7H6O43,4-Dihydroxybenzoic acidProteocatechuic acid |
Procyanidin(Dimer) | Metabolite | pubchem.compound:11250133 | |
3-Hydroxyphenyl propionic acid | Metabolite | pubchem.compound:91 | C9H10O33-Hydroxyphenylpropionic acid3-(3'-hydroxyphenyl)propionic acid |
ω-Phenylacetic acid | Metabolite | pubchem.compound:999 | C8H8O2ω-Phenylacetic acidPhenylacetic acid2-phenylacetic acid 2-phenylethanoate |
Hippuric acid | Metabolite | pubchem.compound:464 | C9H9NO3hippuric acidN-benzoylglycine |
4-hydroxy-5-(3'-hydroxyphenyl)valeric acid | Metabolite | pubchem.compound:52920334 | AKA 5-(3'-hydroxyphenyl)-gamma-hydroxyvaleric acid; 4-Hydroxy-5-(3-hydroxyphenyl)valeric acid |
Dihydroferulic acid | Metabolite | pubchem.compound:14340 | C10H12O43-(4-hydroxy-3-methoxyphenyl)propanoic aciddihydroconiferylate |
5-(3,4-dihydroxyphenyl)pentanoic acid | Metabolite | pubchem.compound:49831816 | C11H14O45-(3,4-dihydroxyphenyl)pentanoic acid5-(3',4'-dihydroxyphenyl)valeric acid |
Homoprotocatechuic acid | Metabolite | pubchem.compound:547 | 3',4'-Dihydroxyphenylacetic acid |
Caffeic acid-3'-sulfate | Metabolite | pubchem.compound:102261219 | |
1-(3,4-Dihydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2-ol | Metabolite | pubchem.compound:21722175 | |
3-(3-Hydroxyphenyl)propionic acid | Metabolite | pubchem.compound:91 | C9H10O33-(3-hydroxyphenyl)-propionic acid3-(3'-hydroxyphenyl)propionic acid 3-hydroxyphenylpropionic acid3'-hydroxy-dihydrocinnamic acidm-hydroxy-dihydrocinnamic acid |
Theaflavin-3,3'-digallate | Metabolite | pubchem.compound:21146795 | C43H32O20[3-hydroxy-5-oxo-4-(3,4,4-trihydroxybenzoyl)oxy-1,8-bis[(2R,3R-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-yl]3,4,5-trihydroxybenzoate |
p-hydroxybenzoic acid | Metabolite | pubchem.compound:135 | C7H6O84-hydroxybenzoic acid4-hydroxybenzenecarboxylic acid |
p-Coumaric acid | Metabolite | pubchem.compound:17450 | C9H8O3Coumaric acid4-hydroxycinnamic acid |
p-Hydroxyphenylacetic acid | Metabolite | pubchem.compound:127 | |
5-(3,4,5-trihydroxyphenyl)valeric acid | Metabolite | pubchem.compound:101786869 | AKA 5-(3,4,5-Trihydroxyphenyl)pentanoic acid (valeric is also known as pentanoic) |
(+)Epiatechin | Metabolite | pubchem.compound:12309508 | |
(-)-Epicatechin 3-O-gallate | Metabolite | pubchem.compound:65064 | C22H18O11[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl]3,4,5-trihydroxybenzoateEpigallocatechingallate |
Vanillic acid | Metabolite | pubchem.compound:8468 | C8H8O4vanillic acid3-methoxy-4-hydroxybenzoic acidp-vanillic acid4-hydroxy-3-methoxybenzoic acid |
5-(3'hydroxyphenyl)-gamma-hydroxyvaleric acid 4'-O-glucuronide | Metabolite | inchikey:LLKUARGHNZMSRT-UHFFFAOYNA-N | AKA 5-(3'hydroxyphenyl)- gamma-hydroxyvaleric acid 4'-O-glucuronide; found in PhytoHub https://phytohub.eu/entries/PHUB001745 |
5-[(3-hydroxyphenyl)methyl]oxolan-2-one | Metabolite | pubchem.compound:3028409 | C11H12O25-[(3-hydroxyphenyl)methyl]oxolan-2-one5-(3'-hydroxyphenyl)-gamma-valerolactone |
4-hydroxyhippuric acid | Metabolite | pubchem.compound:151012 | C9H9NO4[(4-hydroxyphenyl)formamido]acetic acid4-hydroxyhippuric acid4'-Hydroxyhippuric acidN-(4-hydroxybenzoyl)glycine |
3-(3-hydroxyphenyl)-3-hydroxypropanoic acid | Metabolite | pubchem.compound:102959 | |
(S)-4-Hydroxy-5-(3,4,5-trihydroxyphenyl) valeric acid | Metabolite | pubchem.compound:101900149 | |
5-(3',5')-Dihydroxyphenyl-gamma-valerolactone | Metabolite | hmdb:HMDB0029187 | |
Ferulic acid-4'-sulfate | Metabolite | pubchem.compound:6305574 | C10H10O7S(2E)-3-[3-methoxy-4-(sulfooxy)phenyl]prop-2-enoic acidtrans-Ferulic acid sulfate |
4-hydroxy-5-(3',4'-dihydroxyphenyl)valeric acid | Metabolite | pubchem.compound:124202072 | AKA 4-Hydroxy-5-(3',4'-dihydroxyphenyl)-valeric acid-O-glucuronide |
Isoferulic acid | Metabolite | pubchem.compound:736189 | C10H10O4(E )-3-(3-hydroxy-4-methoxyphenyl)prop-2-enoic acid4-methylcaffeic acid |
Gallic acid | Metabolite | pubchem.compound:370 | C7H6O53,4,5-trihydroxybenzoic acid |
(S)-4-hydroxy-5-(3,5-dihydroxyphenyl) valeric acid | Metabolite | pubchem.compound:101900150 | |
5-(Hydroxyphenyl)-gamma-valerolactone-O-sulphate | Metabolite | hmdb:HMDB0059993 | |
3-(4'-hydroxyphenyl)propionic acid | Metabolite | pubchem.compound:91 | |
p-hydroxybenzoic acid | Metabolite | pubchem.compound:135 | C7H6O8p-hydroxybenzoic acid4-hydroxybenzoic acid4-hydroxybenzenecarboxylic acid |
Benzoic acid-4-sulfate | Metabolite | pubchem.compound:18690341 | AKA 4-Sulfooxybenzoic acid |
4-Hydroxyhippuric acid | Metabolite | pubchem.compound:151012 | C9H9NO4[(4-hydroxyphenyl)formamido]acetic acid4-Hydroxyhippuric acid4'-Hydroxyhippuric acid N-(4-hydroxybenzoyl)glycine |
Homovanillic acid | Metabolite | pubchem.compound:1738 | C9H10O4Homovanillic acid(4-hydroxy-3-methoxyphenyl)acetic acid3-methoxy-4-hydroxyphenylacetic acid 3-methoxy-4-hydroxyphenylacetate3'-methoxy-4'-hydroxyphenylacetic |
1-(3',4'-Dihydroxyphenyl)-3-(2'',4''-6''-trihydroxyphenyl)propan-2-ol | Metabolite | pubchem.compound:21722175 | C15H16O62-[3-(3,4-dihydroxyphenyl)-2-hydroxypropyl]benzene-1,3,5-triol |
Catechin | Metabolite | pubchem.compound:1203 | C15H14O62-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol |
3-(3-Hydroxyphenyl)propionic acid | Metabolite | pubchem.compound:91 | C9H10O33-(3-hydroxyphenyl)-propionic acid3-(3'-hydroxyphenyl)propionic acid3-hydroxyphenylpropionic acid3'-hydroxy-dihydrocinnamic acidm-hydroxy-dihydrocinnamic acid |
3-(4'-Hydroxyphenyl)propionic acid | Metabolite | pubchem.compound:91 | |
CoA | Metabolite | chebi:15346 | |
4-Hydroxybenzoic acid 3-sulfate | Metabolite | pubchem.compound:76974408 | |
Gallocatechin | Metabolite | pubchem.compound:65084 | C15H14O7(2R,3R)-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol) |
4-Hydroxyhippuric acid | Metabolite | pubchem.compound:151012 | C9H9NO4[(4-hydroxyphenyl)formamido]acetic acid4-Hydroxyhippuric acid4'-Hydroxyhippuric acidN-(4-hydroxybenzoyl)glycine |
3-Hydroxyhippuric acid | Metabolite | pubchem.compound:450268 | C9H9NO43-hydroxyhippuric acid3-hydroxyhippuric acidN-(3-hydroxybenzoyl)glucine |
3-Hydroxybenzoic acid | Metabolite | pubchem.compound:7420 | C7H6O33-hdroxybenzoic acidm-hydroxybenzoic acid3-hydroxybenzenecarboxylic acid |
3-O-Methylgallic acid | Metabolite | chebi:28647 | |
Pyrogallol-1-sulfate | Metabolite | pubchem.compound:54110629 | |
Pyrogallol-2-O-glucuronide | Metabolite | pubchem.compound:122553541 | |
Pyrogallol-2-sulfate | Metabolite | pubchem.compound:92013662 | |
(-)-Epicatechin-3'-sulfate | Metabolite | pubchem.compound:124202088 | |
Catechol-O-methyltransferase | GeneProduct | ensembl:ENSG00000093010 | |
UDP-glucuronyltransferase | Protein | eccode:2.4.1.17 |
References
- Structural Elucidation and Quantification of Phenolic Conjugates Present in Human Urine after Tea Intake. van der Hooft JJJ, de Vos RCH, Mihaleva V, Bino RJ, Ridder L, de Roo N, et al. Anal Chem [Internet]. 2012 Aug 2;84(16):7263–71. Available from: http://dx.doi.org/10.1021/ac3017339 DOI Scholia
- The current distribution of CD4+ T-lymphocyte counts among adults in the United States with human immunodeficiency virus infections: estimates based on the experience of the U.S. Army. U.S. Army Retrovirus Research Group. Brundage JF, McNeil JG, Miller RN, Gardner LI Jr, Harrison SM, Hawkes C, et al. J Acquir Immune Defic Syndr (1988). 1990;3(1):92–4. PubMed Europe PMC Scholia
- Identification of (-)-epicatechin metabolites and their metabolic fate in the rat. Okushio K, Suzuki M, Matsumoto N, Nanjo F, Hara Y. Drug Metab Dispos. 1999 Feb;27(2):309–16. PubMed Europe PMC Scholia
- The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats. Tsang C, Auger C, Mullen W, Bornet A, Rouanet JM, Crozier A, et al. Br J Nutr. 2005 Aug;94(2):170–81. PubMed Europe PMC Scholia
- Dietary phenolics: chemistry, bioavailability and effects on health. Crozier A, Jaganath IB, Clifford MN. Nat Prod Rep. 2009 Aug;26(8):1001–43. PubMed Europe PMC Scholia
- Targeted metabolic profiling of phenolics in urine and plasma after regular consumption of cocoa by liquid chromatography-tandem mass spectrometry. Urpi-Sarda M, Monagas M, Khan N, Llorach R, Lamuela-Raventós RM, Jáuregui O, et al. J Chromatogr A. 2009 Oct 23;1216(43):7258–67. PubMed Europe PMC Scholia
- Green tea flavan-3-ols: colonic degradation and urinary excretion of catabolites by humans. Roowi S, Stalmach A, Mullen W, Lean MEJ, Edwards CA, Crozier A. J Agric Food Chem. 2010 Jan 27;58(2):1296–304. PubMed Europe PMC Scholia
- In vitro bioconversion of polyphenols from black tea and red wine/grape juice by human intestinal microbiota displays strong interindividual variability. Gross G, Jacobs DM, Peters S, Possemiers S, van Duynhoven J, Vaughan EE, et al. J Agric Food Chem. 2010 Sep 22;58(18):10236–46. PubMed Europe PMC Scholia
- Bioavailability of dietary flavonoids and phenolic compounds. Crozier A, Del Rio D, Clifford MN. Mol Aspects Med. 2010 Dec;31(6):446–67. PubMed Europe PMC Scholia
- Metabolism of green tea catechins by the human small intestine. Schantz M, Erk T, Richling E. Biotechnol J. 2010 Oct;5(10):1050–9. PubMed Europe PMC Scholia
- Berry flavonoids and phenolics: bioavailability and evidence of protective effects. Del Rio D, Borges G, Crozier A. Br J Nutr. 2010 Oct;104 Suppl 3:S67-90. PubMed Europe PMC Scholia
- Isolation of catechin-converting human intestinal bacteria. Kutschera M, Engst W, Blaut M, Braune A. J Appl Microbiol. 2011 Jul;111(1):165–75. PubMed Europe PMC Scholia
- Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Monagas M, Urpi-Sarda M, Sánchez-Patán F, Llorach R, Garrido I, Gómez-Cordovés C, et al. Food Funct. 2010 Dec;1(3):233–53. PubMed Europe PMC Scholia
- Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Ottaviani JI, Momma TY, Kuhnle GK, Keen CL, Schroeter H. Free Radic Biol Med. 2012 Apr 15;52(8):1403–12. PubMed Europe PMC Scholia
- Bioavailability of coffee chlorogenic acids and green tea flavan-3-ols. Del Rio D, Stalmach A, Calani L, Crozier A. Nutrients. 2010 Aug;2(8):820–33. PubMed Europe PMC Scholia
- Elucidation of (-)-epicatechin metabolites after ingestion of chocolate by healthy humans. Actis-Goretta L, Lévèques A, Giuffrida F, Romanov-Michailidis F, Viton F, Barron D, et al. Free Radic Biol Med. 2012 Aug 15;53(4):787–95. PubMed Europe PMC Scholia
- Human studies on the absorption, distribution, metabolism, and excretion of tea polyphenols. Clifford MN, van der Hooft JJJ, Crozier A. Am J Clin Nutr. 2013 Dec;98(6 Suppl):1619S-1630S. PubMed Europe PMC Scholia
- The pharmacokinetics of anthocyanins and their metabolites in humans. de Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, et al. Br J Pharmacol. 2014 Jul;171(13):3268–82. PubMed Europe PMC Scholia
- Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update. Rodriguez-Mateos A, Vauzour D, Krueger CG, Shanmuganayagam D, Reed J, Calani L, et al. Arch Toxicol. 2014 Oct;88(10):1803–53. PubMed Europe PMC Scholia
- A comprehensive evaluation of the [2-14C](-)-epicatechin metabolome in rats. Borges G, van der Hooft JJJ, Crozier A. Free Radic Biol Med. 2016 Oct;99:128–38. PubMed Europe PMC Scholia
- Anthocyanins and Flavanones Are More Bioavailable than Previously Perceived: A Review of Recent Evidence. Kay CD, Pereira-Caro G, Ludwig IA, Clifford MN, Crozier A. Annu Rev Food Sci Technol. 2017 Feb 28;8:155–80. PubMed Europe PMC Scholia
- Bioavailability of Black Tea Theaflavins: Absorption, Metabolism, and Colonic Catabolism. Pereira-Caro G, Moreno-Rojas JM, Brindani N, Del Rio D, Lean MEJ, Hara Y, et al. J Agric Food Chem. 2017 Jul 5;65(26):5365–74. PubMed Europe PMC Scholia