THE METABOLISM OF AMINO ACIDS, PEPTIDES, AND DISULFIDES IN LYSOSOMES OF FIBROBLASTS CULTURED FROM NORMAL INDIVIDUALS AND THOSE WITH CYSTINOSIS

Abstract

The metabolism of amino acids, peptides, and disulfides has been investigates in cultured skin fibroblasts from normal individuals and patients with cystinosis. Human fibroblast lysosomes closely resemble the lysosomes of mouse peritoneal macrophages in having an apparent permeability barrier to amino acids and peptides with molecular weights of greater than 220–230. Cystinotic and normal cells behave similarly in this regard. Normal cells do not undergo lysosomal swelling when exposed to cysteine-penicillamine disulfides, while cystinotic cells are prominently vacuolized under these conditions. Normal lysosomes may have a specific mechanism for the disposal of cystine, and deficient activity of this mechanism in cystinotic lysosomes could result in cystine storage therein. The demonstration that human fibroblasts can be used conveniently to study lysosomal metabolism of small substrates may facilitate investigations of these aspects of lysosomal function in a variety of genetic diseases of man.