Is leucine an allosteric modulator of the lysine transporter in the intestinal basolateral membrane?
The transport of the dibasic amino acid L-lysine was investigated using basolateral membrane vesicles prepared from rat jejunal mucosal scrapings. The majority of the carrier-mediated transport was unaffected by the presence of sodium in the incubation medium, but voltage clamping of the vesicles did increase lysine uptake, indicating an associated movement of charge. Kinetic analysis of lysine influx and efflux showed the system to be symmetrical, but although the Vmax was comparable to other amino acid transport systems in this membrane, the dissociation constant for the overall reaction (KT) was an order of magnitude larger. This low affinity for lysine would explain the relatively slow rate of transport of this amino acid across the basolateral membrane. Competition experiments indicated that this system has a relatively narrow specificity carrying only lysine, arginine, ornithine, and histidine. In contrast the presence of L-leucine caused a marked stimulation of lysine efflux and influx across the vesicles. This effect was observed with leucine concentrations as low as 0.1 microM. It is concluded that although the lysine transport system in the basolateral membrane is slow in its basal state it can be rapidly turned on by the presence of L-leucine. The remarkably low concentrations required to do this suggest a possible allosteric interaction between the transporter and this neutral amino acid.
D000494:Allosteric Regulation; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology*; D008239:Lysine / Q000378:metabolism*; D051381:Rats; D014634:Valinomycin / Q000494:pharmacology
D002352:Carrier Proteins; D014634:Valinomycin; D007930:Leucine; D008239:Lysine