A kinetic study of the interactions between amino acids and monosaccharides at the intestinal brush-border membrane.
1. The influx of amino acids into guinea-pig intestinal rings in vitro is inhibited by monosaccharides, and that of monosaccharides by amino acids. Two hypotheses have been proposed to account for these heterologous interactions. According to the first, the cis hypothesis, there is an allosteric interaction between substrates binding to separate but related sites at the outer face of the brush-border membrane matrix. In contrast, the trans hypothesis envisages the interaction to result from a partial dissipation of the electrochemical sodium gradient due to the cotransport of each substrate with sodium ions. 2. In an attempt to distinguish between the merits of the two hypotheses, we examined the kinetics of the inhibition of phenylalanine influx by two sugars of widely different affinities, galactose and beta-methylglucoside. Since beta-methylglucoside carries more sodium into the cell than galactose, the trans hypothesis would predict it to be the stronger inhibitor, but in fact the opposite result is found. 3. Equations were developed to describe the inhibitions in accordance with the cis hypothesis. The satisfactory agreement between experimental observations and theoretical predictions provides support for the applicability of the model. Further implications of the polyfunctional carrier model are discussed.
D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D004347:Drug Interactions; D005690:Galactose / Q000378:metabolism*; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption; D007700:Kinetics; D008757:Methylglucosides / Q000378:metabolism*; D008759:Methylglycosides / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism*; D008954:Models, Biological; D010649:Phenylalanine / Q000378:metabolism*
D008757:Methylglucosides; D008759:Methylglycosides; D010649:Phenylalanine; D005690:Galactose