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

Abstract

l-Aspartate and l-glutamate are transported into human fibroblast lysosomes by a single, low K m, Na +-independent transport system, which has been provisionally named lysosomal system d. This system resembles the Na +-dependent plasma membrane system x 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 x AG −; (2) the anion l-homocysteate is not accepted by system x AG −, but is an effective inhibitor of lysosomal system d; (3) N-methyl, α-methyl, and ω-hydroxamate derivatives of both aspartate and glutamate inhibit lysosomal system d, but only the aspartate derivatives are accepted by system x AG −; (4) lysosomal system d shows a preference for the substrate amino group in the α-position, a preference not seen for system x 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.