Structural Requirements of Substrates for Stereoselective Monocarboxylate Transport in Caco‐2 Cells

This study was designed to characterize the structural requirements for stereoselective transport of substrates by the monocarboxylate transporters (proton cotransporter and anion antiporter) of Caco-2 cells by examining the inhibitory effect of the optical isomers of chiral monocarboxylic acids and the transcellular transport of two Chiral monocarboxylic acids and the transcellular transport of two Chiral monocarboxylic acids. In the presence of a proton gradient the transport of a trace concentration (1 μM) of l-lactic acid in Caco-2 cells was inhibited stereoselectively by 2-hydroxy- and 2-methoxymonocarboxylic acids, for example S- and R-mandelic and S- and R-2-methoxypropionic acids. Similar results were obtained in the presence of a bicarbonate ion gradient. Transport was also inhibited non-stereoselectively by several other monocarboxylic acids, for example S- and R-2-phenylpropionic acids. Transport of both S- and R-mandelic acids apparently involved saturable and non-saturable processes. For the saturable process affinity was higher and capacity lower for S-mandelic acid than for the R isomer, whereas no stereoselectivity was observed for transport of S- and R-2-phenylpropionic acids. It is suggested that a 2-hydroxyl or 2-methoxy group is important for specific stereoselective carrier-mediated transport of monocarboxylic acids across intestinal epithelial cells.