Detection and characterization of carrier-mediated cationic amino acid transport in lysosomes of normal and cystinotic human fibroblasts. Role in therapeutic cystine removal

Journal Article · Thu Apr 25 00:00:00 EST 1985 · J. Biol. Chem.; (United States)

OSTI ID:5023528

Pisoni, R L; Thoene, J G; Christensen, H N

The discovery of a trans-stimulation property associated with lysine exodus from lysosomes of human fibroblasts has enabled us to characterize a system mediating the transport of cationic amino acids across the lysosomal membrane of human fibroblasts. The cationic amino acids arginine, lysine, ornithine, diaminobutyrate, histidine, 2-aminoethylcysteine, and the mixed disulfide of cysteine and cysteamine all caused trans-stimulation of the exodus of radiolabeled lysine from the lysosomal fraction of human fibroblasts at pH 6.5. In contrast, neutral and acidic amino acids did not affect the rate of lysine exodus. Trans-stimulation of lysine exodus was observed over the pH range from 5.5 to 7.6, was specific for the L-isomer of the cationic amino acid, and was intolerant to methylation of the alpha-amino group of the amino acid. The lysosomotropic amine, chloroquine, greatly retarded lysine exodus, whereas the presence of sodium ion was without effect. The specificity and lack of Na+ dependence of this lysosomal transport system is similar to that of System y+ present on the plasma membrane of human fibroblasts. An important mechanism by which cysteamine treatment of cystinosis allows cystine escape from lysosomes may be the ability of the mixed disulfide of cysteine and cysteamine formed by sulfhydryl-disulfide exchange to migrate by this newly discovered system mediating cationic amino acid transport.

• Research Organization: Univ. of Michigan Medical School, Ann Arbor
• OSTI ID: 5023528
• Journal Information: J. Biol. Chem.; (United States), Vol. 8
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CYSTINE
MEMBRANE TRANSPORT
LABELLED COMPOUNDS
LYSINE
AMINO ACIDS
ELECTROPHORESIS
FIBROBLASTS
LYSOSOMES
MEA
PH VALUE
AMINES
ANIMAL CELLS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DISULFIDES
DRUGS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANOIDS
RADIOPROTECTIVE SUBSTANCES
SOMATIC CELLS
THIOLS
550201* - Biochemistry- Tracer Techniques