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

Abstract

-Aspartate and -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 xAG-, although these differences have been observed: (1) lysosomal system d recognizes the - as well as the -isomers of both aspartate and glutamate, whereas only for aspartate is the -isomer recognized by system xAG-; (2) the anion -homocysteate is not accepted by system xAG-, 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 xAG-; (4) lysosomal system d shows a preference for the substrate amino group in the [alpha]-position, a preference not seen for system xAG-. 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.