Document Detail


Important differences in cationic amino acid transport by lysosomal system c and system y+ of the human fibroblast.
MedLine Citation:
PMID:  3499437     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Superficial similarities led us to extend our designation for the transport of the plasma membrane for cationic amino acids, y+, to the lysosomal system also serving for such amino acids. Further study on the purified lysosomes of human skin fibroblasts leads us now to redesignate the lysosomal system as c (for cationic), rather than y+, to emphasize important contrasts. Lysosomal uptake of arginine at pH 7.0 was linear during the first 2 min, but attained a steady state in 6 min. This arginine uptake was Na+-independent and was tripled in rate when the lysosomes had first been loaded with the cationic amino acid analog, S-2-aminoethyl-L-cysteine. Uptake was slowed to one-third when 2 mM MgATP was added to the incubation mixture. The following differences in cationic amino acid influx between lysosomal System c and the plasma membrane System y+ became apparent: 1) arginine influx is increased 10-fold by raising the external pH from 5.0 to 7.0. This effect favors net entry of cationic amino acids under the H+ gradient prevailing in vivo. In contrast, arginine uptake across the plasma membrane is insensitive to pH changes in this range. 2) The Km of arginine uptake by lysosomal System c, 0.32 mM, is eight times that for System y+ arginine uptake by the fibroblast. 3) Certain neutral amino acids in the presence of Na+ are accepted as surrogate substrates by System y+, but not by lysosomal system c. 4) Cationic amino acids in which the alpha-amino group is monomethylated or the distal amino group is quaternary, also D-arginine, are recognized by lysosomal System c, whereas System y+ has little affinity for these analogs. This broader substrate specificity of lysosomal system c led us to discover that thiocholine serves to deplete accumulated cystine from cystinotic fibroblasts as effectively as does the therapeutic agent, cysteamine. The quaternary nitrogen of thiocholine renders the mixed disulfide formed when it reacts with cystine unsatisfactory as a substrate for System y+.
Authors:
R L Pisoni; J G Thoene; R M Lemons; H N Christensen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  262     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1987 Nov 
Date Detail:
Created Date:  1987-12-10     Completed Date:  1987-12-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  15011-8     Citation Subset:  IM    
Affiliation:
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / pharmacology
Amino Acids / pharmacology
Arginine / metabolism*
Biological Transport
Cell Fractionation / methods
Cell Line
Cystine / metabolism*
Fibroblasts / metabolism
Humans
Kinetics
Lysosomes / drug effects,  metabolism*,  ultrastructure
Sodium Chloride / pharmacology
Grant Support
ID/Acronym/Agency:
DK25548/DK/NIDDK NIH HHS; DK33281/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 56-65-5/Adenosine Triphosphate; 56-89-3/Cystine; 74-79-3/Arginine; 7647-14-5/Sodium Chloride

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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