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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0024369,
umls-concept:C0037791,
umls-concept:C0066146,
umls-concept:C0205352,
umls-concept:C0231435,
umls-concept:C0332120,
umls-concept:C0332464,
umls-concept:C0560175,
umls-concept:C1441547,
umls-concept:C1704689,
umls-concept:C1706209,
umls-concept:C1707271,
umls-concept:C1880022,
umls-concept:C2244328
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pubmed:issue |
28
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pubmed:dateCreated |
1992-11-16
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pubmed:abstractText |
Studies are presented further characterizing a facilitative system transporting methotrexate (MTX) polyglutamates into lysosomes derived from S180 cells. Initial influx of [3H]MTX + G1 (MTX with 1 additional glutamyl residue) exhibited a slightly alkaline pH optimum (pH 7.7) and was moderately temperature-dependent (Q10 27-37 degrees C = 3.1 +/- 0.1). An analysis of the kinetics of intralysosomal accumulation of [3H]MTX + G1 showed saturation kinetics for initial influx, but linear kinetics for the steady-state level of exchangeable [3H]MTX + G1 at different external concentrations of [3H]MTX + G1. In addition, the system exhibited substantial directional asymmetry with respect to the interaction with MTX + G1 during influx and efflux. Accelerated homo- and heteroexchange diffusion was demonstrated for influx of [3H]MTX + G1, while decelerated homoexchange diffusion was demonstrated for efflux of [3H]MTX + G1 following trans-positioning of MTX + G1 or glutamyl-gamma-glutamate in the opposite compartment. These observations were consistent with a single mobile carrier system mediating influx and efflux of this polyglutamate. Based upon an analysis of competitive interactions with [3H] MTX + G1, this system displayed specificity for MTX-gamma-glutamates, folyl-gamma-polyglutamates, alpha- or gamma-glutamyl peptides and heteropeptides bearing a C-terminal gamma-glutamate but not for MTX or glutamate, themselves. Among polyglutamates, gamma-glutamyl chain length was not a significant factor for transport except in the case of MTX polyglutamates. Overall, our results appear to delineate in the lysosomal membrane a simple mobile carrier system with broad specificity for folyl- or non-folyl-bearing peptides responsible for the transport of MTX polyglutamates.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glutamates,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamine,
http://linkedlifedata.com/resource/pubmed/chemical/Methotrexate,
http://linkedlifedata.com/resource/pubmed/chemical/Polyglutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/methotrexate polyglutamate
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19986-91
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1383199-Animals,
pubmed-meshheading:1383199-Binding, Competitive,
pubmed-meshheading:1383199-Biological Transport, Active,
pubmed-meshheading:1383199-Glutamates,
pubmed-meshheading:1383199-Glutamine,
pubmed-meshheading:1383199-Hydrogen-Ion Concentration,
pubmed-meshheading:1383199-Kinetics,
pubmed-meshheading:1383199-Lysosomes,
pubmed-meshheading:1383199-Methotrexate,
pubmed-meshheading:1383199-Mice,
pubmed-meshheading:1383199-Mice, Inbred C57BL,
pubmed-meshheading:1383199-Mice, Inbred DBA,
pubmed-meshheading:1383199-Polyglutamic Acid,
pubmed-meshheading:1383199-Sarcoma 180,
pubmed-meshheading:1383199-Temperature
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pubmed:year |
1992
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pubmed:articleTitle |
Facilitated transport of methotrexate polyglutamates into lysosomes derived from S180 cells. Further characterization and evidence for a simple mobile carrier system with broad specificity for homo- or heteropeptides bearing a C-terminal glutamyl moiety.
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pubmed:affiliation |
Laboratory for Molecular Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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