Microbial metabolites of ingested caffeic acid are absorbed by the monocarboxylic acid transporter (MCT) in intestinal Caco-2 cell monolayers.
It was previously reported that m-coumaric acid, m-hydroxyphenylpropionic acid (mHPP), and 3,4-dihydroxyphenylpropionic acid (DHPP) are major metabolites of ingested caffeic acid formed by gut microflora and would be transported by the monocarboxylic acid transporter (MCT). We have directly measured their absorption characteristics in Caco-2 cells using a coulometric detection method involving HPLC-ECD. The proton-coupled directional transport of m-coumaric acid, mHPP, and DHPP was observed, and the transport was inhibited by an MCT substrate. The permeation of m-coumaric acid and mHPP was concentration-dependent and saturable: The Michaelis constant for m-coumaric acid and mHPP was 32.5 and 12.9 mM, respectively, and the maximum velocity for m-coumaric acid and mHPP was 204.3 and 91.2 nmol (min)(-1) (mg protein)(-1), respectively. By contrast, the permeation of DHPP was nonsaturable even at 30 mM and was inversely correlated with the paracellular permeability of Caco-2 cells. Our results demonstrate that these compounds are absorbed by the MCT, although DHPP is mainly permeated across Caco-2 cells via the paracellular pathway. MCT-mediated absorption of phenolic compounds per se and their colonic metabolites would exert significant impact on human health.
Applied Bioresearch Center, Research & Development Department, Kirin Brewery Company, Ltd., 3 Miyaharacho, Takasaki-shi, Gunma 370-1295, Japan. konishiy@kirin.co.jp
Yutaka
Y
Konishi
Shoko
S
Kobayashi
D001692:Biological Transport; D018938:Caco-2 Cells; D002109:Caffeic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003373:Coumaric Acids / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000382:microbiology*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D002109:Caffeic Acids; D003373:Coumaric Acids; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C000995:3,4-dihydroxyphenylpropionic acid; C043332:3-coumaric acid; C038547:dihydro-3-coumaric acid; C040048:caffeic acid