Linked Life Data

10598550

Source:http://linkedlifedata.com/resource/pubmed/id/10598550

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Suppl 6
pubmed:dateCreated
1999-12-21
pubmed:abstractText
Transport of folates and antifolates in most cells is mediated by the reduced folate carrier (RFCI), an anion exchanging concentrative process, which is opposed by independent exit pump(s) that are directly coupled to energy metabolism. The balance of these processes governs the free intracellular folate level that is the substrate for folylpolyglutamate synthetase and determines the rate of metabolism of many folates and antifolates to polyglutamate derivatives. The RFCI has a high affinity for new-generation antifolates, but the relationship between transport and polyglutamylation for all these compounds has not, as yet, been defined. Analysis of mutations in RFCI indicate highly selective functional changes in binding affinity and/or carrier mobility, raising the possibilities that (1) enhanced transport and accumulation of natural folates can result in resistance to antifolate inhibitors of purine and pyrimidine synthesis by blocking their polyglutamylation to active derivatives, or by competition at the target enzyme site without substantial changes in antifolate transport, and (2) transport-related resistance to one antifolate might not produce comparable cross-resistance to another. Impaired export pump function, which results in enhanced accumulation of folates in cells and inhibition of antifolate polyglutamylation, represents another potential mechanism of resistance to new-generation antifolates. Folate receptor-mediated transport is another route of entry of folates and antifolates into cells, but its importance has not been well-defined. Finally, a low pH transport mechanism is present in a variety of mammalian cell lines. However, its relationship to RFCI and other low pH epithelial transporters and its ability to transport new-generation antifolates remain to be established.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0093-7754
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-23
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Recent advances in the understanding of the mechanism of membrane transport of folates and antifolates.
pubmed:affiliation
Department of Medicine, Albert Einstein College of Medicine, Comprehensive Cancer Center, Albert Einstein College of Medicine Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't