Document Detail


In situ kinetic characterization of methylthioadenosine transport by the adenosine transporter (P2) of the African Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense.
MedLine Citation:
PMID:  11226379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
African trypanosomes are parasitic flagellates that live in the connective tissues of the host. Trypanosomes must obtain from their host adenine/adenosine and other nucleosides that can be salvaged through enzymatic cleavage. Methylthioadenosine (MTA) is a byproduct of polyamine metabolism, formed from the donation of an aminopropyl moiety by decarboxylated S-adenosylmethionine (dcAdoMet) to form spermidine. MTA is then cleaved phosphorolytically by MTA phosphorylase to methylthioribose-1-phosphate (MTR-1-P) and adenine. The uptake of MTA was compared with that of adenosine in two strains: Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense. The K(m) values for MTA and adenosine (with 5 mM inosine) transport by T. b. brucei were 1.4 and 0.175 mM, and the V(max) values were 70 and 7.8 micromol/L/min, respectively. The K(m) values for T. b. rhodesiense MTA and adenosine (with 5 mM inosine) transport were 1.2 and 0.11 mM, and the V(max) values were 52.6 and 2.9 micromol/L/min, respectively. Since MTA was not competitive with either AdoMet (100 microM), inosine (100 microM), or the methionine precursor ketomethylthiobutyrate (100 microM), it appears that MTA enters through the P(2) (adenosine/adenine) transport site. From this study and our previous work, we determined that these organisms transport adenylated intermediates of methionine metabolism found in sera for purine salvage and as an ancillary source of methionine. The significant ability of African trypanosomes to transport MTA and related intermediates is an important consideration in the design and development of selective chemotherapeutic agents.
Authors:
B Goldberg; D Rattendi; D Lloyd; J R Sufrin; C J Bacchi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  61     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-06     Completed Date:  2001-03-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  449-57     Citation Subset:  IM    
Affiliation:
Department of Biology, St. Francis College, 180 Remsen Street, Brooklyn Heights, 11201, Brooklyn, NY, USA. bg43@nyu.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine / analogs & derivatives*,  metabolism,  pharmacokinetics*
Animals
Binding, Competitive
Biological Transport
Carrier Proteins / metabolism*
Kinetics
Membrane Proteins / metabolism*
Methionine / metabolism
Nucleoside Transport Proteins
Polyamines / metabolism
S-Adenosylhomocysteine / metabolism
Thionucleosides / metabolism,  pharmacokinetics*
Trypanosoma brucei brucei / metabolism*
Trypanosoma brucei rhodesiense / metabolism*
Grant Support
ID/Acronym/Agency:
AI 17340/AI/NIAID NIH HHS; AI 32975/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/5'-deoxy-5'-(hydroxyethylthio)adenosine; 0/Carrier Proteins; 0/Membrane Proteins; 0/Nucleoside Transport Proteins; 0/Polyamines; 0/Thionucleosides; 4105-39-9/2-methylthioadenosine; 58-61-7/Adenosine; 63-68-3/Methionine; 979-92-0/S-Adenosylhomocysteine

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


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