Mammalian amino acid transport system y(+) revisited: Specificity and cation dependence of the interaction with neutral amino acids

A reevaluation of the specificity of system y(+), the classical transporter for cationic amino acids is presented. System y(+) has been defined as a t ransporter for cationic amino acids that binds neutral amino acids with low er affinity in the presence of Na+. The discovery of other transporters for cationic amino has suggested that some properties, originally attributed t o system y(+), may relate to other transport systems. Uncertainty concerns mainly, the affinity for neutral amino acids and the cation dependence of t his interaction. Neutral amino acids (13 analogues tested) were found to bi nd to system y(+) in human erythrocytes with very low affinity. Inhibition constants (K-iy, mM) ranged between 14.2 mM and >400 mM, and the strength o f interaction was similar in the presence of Na+, K+ or Li+ (145 mM). In ch oline medium, no interaction was detected up to 20 mM of the neutral amino acid. Guanidinium ion (5 mM, osmolarity maintained with choline) potentiate d neutral amino acid binding; the effect was most important in the case of L-norvaline which aligned with guanidinium ion is equivalent to arginine. T his suggests cooperative interaction at the substrate site. The specificity of system y(+) was shown to be clearly distinct from that of system y(+)L, a cationic amino acid transporter that accepts neutral amino acids with hi gh affinity in the presence of Na+ and which influenced the classical defin ition of system y(+).