The binding specificity of amino acid transport system y+L in human erythrocytes is altered by monovalent cations.
System y+L is a broad-scope amino acid transporter which binds and translocates cationic and neutral amino acids. Na+ replacement with K+ does not affect lysine transport, but markedly decreases the affinity of the transporter for L-leucine and L-glutamine. This observation suggests that the specificity of system y+L varies depending on the ionic composition of the medium. Here we have studied the interaction of the carrier with various amino acids in the presence of Na+, K+, Li+ and guanidinium ion. In agreement with the prediction, the specificity of system y+L was altered by the monovalent cations. In the presence of Na+, L-leucine was the neutral amino acid that interacted more powerfully. Elongation of the side chain (glycine - L-norleucine) strengthened binding. In contrast, bulkiness at the level of the beta carbon was detrimental. In K+, the carrier behaved as a cationic amino acid specific carrier, interacting weakly with neutral amino acids. Li+ was found to potentiate neutral amino acid binding and in general the apparent affinities were higher than in Na+; elongation of the nonpolar side chain made a more important contribution to binding and the carrier was more tolerant towards beta carbon substitution. Guanidinium stimulated the interaction of the carrier with neutral amino acids, but the effect was restricted to certain analogues (e.g., L-leucine, L-glutamine, L-methionine). Thus, in the presence of guanidinium, the carrier discriminates sharply among different neutral amino acids. The results suggest that the monovalent cations stabilize different carrier conformations.
Angelo
S
S
Department of Physiology and Biophysics, Faculty of Medicine, University of Chile, Santiago, Chile.
Irarrázabal
C
C
Devés
R
R
D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002414:Cations, Monovalent / Q000378:metabolism* / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002352:Carrier Proteins; D002414:Cations, Monovalent; D008565:Membrane Proteins; D012964:Sodium; D008239:Lysine; D011188:Potassium