Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-4-11
pubmed:databankReference
pubmed:abstractText
Protozoan parasites of the trypanosomatid genus Leishmania are pteridine auxotrophs, and have evolved an elaborate and versatile pteridine salvage network capable of accumulating and reducing pteridines. This includes biopterin and folate transporters (BT1 and FT1), pteridine reductase (PTR1), and dihydrofolate reductase-thymidylate synthase (DHFR-TS). Notably, PTR1 is a novel alternative pteridine reductase whose activity is resistant to inhibition by standard antifolates. In cultured promastigote parasites, PTR1 can function as a metabolic by-pass under conditions of DHFR inhibition and thus reduce the efficacy of chemotherapy. To test whether pteridine salvage occurred in the infectious stage of the parasite, we examined several pathogenic species of Leishmania and the disease-causing amastigote stage that resides within human macrophages. To accomplish this we developed a new sensitive HPLC-based assay for PTR1 activity. These studies established the existence of the pteridine salvage pathway throughout the infectious cycle of Leishmania, including amastigotes. In general, activities were not well correlated with RNA transcript levels, suggesting the occurrence of at least two different modes of post-transcriptional regulation. Thus, pteridine salvage by amastigotes may account for the clinical inefficacy of antifolates against leishmaniasis, and ultimately provide insights into how this may be overcome in the future.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Biopterin, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes, http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, http://linkedlifedata.com/resource/pubmed/chemical/Protozoan Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Pteridines, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydrofolate Dehydrogenase, http://linkedlifedata.com/resource/pubmed/chemical/Thymidylate Synthase, http://linkedlifedata.com/resource/pubmed/chemical/pteridine reductase, http://linkedlifedata.com/resource/pubmed/chemical/thymidylate synthase-dihydrofolate...
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
199-213
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11295174-Animals, pubmed-meshheading:11295174-Biopterin, pubmed-meshheading:11295174-Carrier Proteins, pubmed-meshheading:11295174-Chromatography, High Pressure Liquid, pubmed-meshheading:11295174-Folic Acid, pubmed-meshheading:11295174-Folic Acid Antagonists, pubmed-meshheading:11295174-Gene Expression Regulation, Developmental, pubmed-meshheading:11295174-Humans, pubmed-meshheading:11295174-Leishmania, pubmed-meshheading:11295174-Leishmaniasis, pubmed-meshheading:11295174-Membrane Transport Proteins, pubmed-meshheading:11295174-Molecular Sequence Data, pubmed-meshheading:11295174-Multienzyme Complexes, pubmed-meshheading:11295174-Oxidoreductases, pubmed-meshheading:11295174-Protozoan Proteins, pubmed-meshheading:11295174-Pteridines, pubmed-meshheading:11295174-RNA, Messenger, pubmed-meshheading:11295174-Tetrahydrofolate Dehydrogenase, pubmed-meshheading:11295174-Thymidylate Synthase
pubmed:year
2001
pubmed:articleTitle
Pteridine salvage throughout the Leishmania infectious cycle: implications for antifolate chemotherapy.
pubmed:affiliation
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.