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In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans.
J Nutr Biochem. 2010 Nov; 21(11):1060-8.JN

Abstract

Hydroxycinnamic acids are a class of phenolic antioxidants found widely in dietary plants. Their biotransformation in the human organism primarily involves Phase II conjugation reactions. In this study, activities of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) towards major dietary hydroxycinnamic acids (caffeic, dihydrocaffeic, dihydroferulic, ferulic and isoferulic acids) were investigated. Conjugate formation was evaluated using human liver and intestinal S9 homogenates, and in vitro characterization was carried out using recombinant human UGTs and SULTs. Analysis of the kinetics of hydroxycinnamic acid conjugation in human S9 homogenates revealed that intrinsic clearance (V(max)/K(m)) is much greater for sulfation than for glucuronidation. Assessment of activity using a panel of recombinant human SULTs showed that SULT1A1 is most active in the sulfation of caffeic, dihydrocaffeic and isoferulic acids, while SULT1E1 is most active in the sulfation of ferulic and dihydroferulic acids. Only isoferulic acid was significantly glucuronidated by human liver S9 homogenates, explained by the high activity of liver-specific UGT1A9. Studies on the kinetics of active SULTs and UGTs demonstrated a markedly lower K(m) for SULTs. To further corroborate our findings, we carried out an intervention study in healthy humans to determine the hydroxycinnamic acid conjugates in urine after consumption of hydroxycinnamate-rich coffee (200 ml). Analysis showed that sulfates are the main conjugates in urine, with the exception of isoferulic acid, which is mainly glucuronidated. These data suggest that sulfates are the predominant hydroxycinnamic acid conjugates in humans, and that SULT mediated sulfation is a major factor determining the bioavailability of hydroxycinnamic acids in vivo.

Authors+Show Affiliations

School of Food Science and Nutrition, University of Leeds, LS29JT Leeds, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19954949

Citation

Wong, Chi Chun, et al. "In Vitro and in Vivo Conjugation of Dietary Hydroxycinnamic Acids By UDP-glucuronosyltransferases and Sulfotransferases in Humans." The Journal of Nutritional Biochemistry, vol. 21, no. 11, 2010, pp. 1060-8.
Wong CC, Meinl W, Glatt HR, et al. In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans. J Nutr Biochem. 2010;21(11):1060-8.
Wong, C. C., Meinl, W., Glatt, H. R., Barron, D., Stalmach, A., Steiling, H., Crozier, A., & Williamson, G. (2010). In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans. The Journal of Nutritional Biochemistry, 21(11), 1060-8. https://doi.org/10.1016/j.jnutbio.2009.09.001
Wong CC, et al. In Vitro and in Vivo Conjugation of Dietary Hydroxycinnamic Acids By UDP-glucuronosyltransferases and Sulfotransferases in Humans. J Nutr Biochem. 2010;21(11):1060-8. PubMed PMID: 19954949.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans. AU - Wong,Chi Chun, AU - Meinl,Walter, AU - Glatt,Hans-Rudolf, AU - Barron,Denis, AU - Stalmach,Angélique, AU - Steiling,Heike, AU - Crozier,Alan, AU - Williamson,Gary, Y1 - 2009/12/01/ PY - 2009/07/13/received PY - 2009/08/26/revised PY - 2009/09/04/accepted PY - 2009/12/4/entrez PY - 2009/12/4/pubmed PY - 2011/1/29/medline SP - 1060 EP - 8 JF - The Journal of nutritional biochemistry JO - J Nutr Biochem VL - 21 IS - 11 N2 - Hydroxycinnamic acids are a class of phenolic antioxidants found widely in dietary plants. Their biotransformation in the human organism primarily involves Phase II conjugation reactions. In this study, activities of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) towards major dietary hydroxycinnamic acids (caffeic, dihydrocaffeic, dihydroferulic, ferulic and isoferulic acids) were investigated. Conjugate formation was evaluated using human liver and intestinal S9 homogenates, and in vitro characterization was carried out using recombinant human UGTs and SULTs. Analysis of the kinetics of hydroxycinnamic acid conjugation in human S9 homogenates revealed that intrinsic clearance (V(max)/K(m)) is much greater for sulfation than for glucuronidation. Assessment of activity using a panel of recombinant human SULTs showed that SULT1A1 is most active in the sulfation of caffeic, dihydrocaffeic and isoferulic acids, while SULT1E1 is most active in the sulfation of ferulic and dihydroferulic acids. Only isoferulic acid was significantly glucuronidated by human liver S9 homogenates, explained by the high activity of liver-specific UGT1A9. Studies on the kinetics of active SULTs and UGTs demonstrated a markedly lower K(m) for SULTs. To further corroborate our findings, we carried out an intervention study in healthy humans to determine the hydroxycinnamic acid conjugates in urine after consumption of hydroxycinnamate-rich coffee (200 ml). Analysis showed that sulfates are the main conjugates in urine, with the exception of isoferulic acid, which is mainly glucuronidated. These data suggest that sulfates are the predominant hydroxycinnamic acid conjugates in humans, and that SULT mediated sulfation is a major factor determining the bioavailability of hydroxycinnamic acids in vivo. SN - 1873-4847 UR - https://www.unboundmedicine.com/medline/citation/19954949/In_vitro_and_in_vivo_conjugation_of_dietary_hydroxycinnamic_acids_by_UDP_glucuronosyltransferases_and_sulfotransferases_in_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0955-2863(09)00192-2 DB - PRIME DP - Unbound Medicine ER -