Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

In situ kinetic characterization of methylthioadenosine transport by the adenosine transporter (P2) of the African Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense

Goldberg, Burt, Rattendi, Donna, Lloyd, David, Sufrin, Janice R. and Bacchi, Cyrus J. 2001. In situ kinetic characterization of methylthioadenosine transport by the adenosine transporter (P2) of the African Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense. Biochemical Pharmacology 61 (4) , pp. 449-457. 10.1016/S0006-2952(00)00560-8

Full text not available from this repository.

Abstract

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 Km values for MTA and adenosine (with 5 mM inosine) transport by T. b. brucei were 1.4 and 0.175 mM, and the Vmax values were 70 and 7.8 μmol/L/min, respectively. The Km values for T. b. rhodesiense MTA and adenosine (with 5 mM inosine) transport were 1.2 and 0.11 mM, and the Vmax values were 52.6 and 2.9 μmol/L/min, respectively. Since MTA was not competitive with either AdoMet (100 μM), inosine (100 μM), or the methionine precursor ketomethylthiobutyrate (100 μM), it appears that MTA enters through the P2 (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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: African trypanosomes; Methionine synthesis; Nucleoside transport; Kinetic analysis
Publisher: Elsevier
ISSN: 0006-2952
Last Modified: 04 Jun 2017 06:36
URI: http://orca.cf.ac.uk/id/eprint/62705

Cited 6 times in Web of Science. View in Web of Science.

Actions (repository staff only)

Edit Item Edit Item