Characterization of a transport system for anionic amino acids in human fibroblast lysosomes.

L-Aspartate and L-glutamate are transported into human fibroblast lysosomes by a single, low Km, Na(+)-independent transport system, which has been provisionally named lysosomal system d. This system resembles the Na(+)-dependent plasma membrane system chi-AG, although these differences have been observed: (1) lysosomal system d recognizes the D- as well as the L-isomers of both aspartate and glutamate, whereas only for aspartate is the D-isomer recognized by system chi-AG; (2) the anion L-homocysteate is not accepted by system chi-AG, but is an effective inhibitor of lysosomal system d; (3) N-methyl, alpha-methyl, and omega-hydroxamate derivatives of both aspartate and glutamate inhibit lysosomal system d, but only the aspartate derivatives are accepted by system chi-AG; (4) lysosomal system d shows a preference for the substrate amino group in the alpha-position, a preference not seen for system chi-AG. These points imply differences at the two recognition sites with respect to substrate length, size, and rotation, with the lysosomal site generally being the less restrictive.