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Báo cáo khoa học: A comparative study of methylglyoxal metabolism in trypanosomatids

The glyoxalase system, comprising the metalloenzymes glyoxalase I (GLO1) and glyoxalase II (GLO2), is an almost universal metabolic path-way involved in the detoxification of the glycolytic byproduct methylglyox-al to d-lactate. | A comparative study of methylglyoxal metabolism in trypanosomatids Neil Greig Susan Wyllie Stephen Patterson and Alan H. Fairlamb Division of BiologicalChemistry and Drug Discovery Wellcome Trust Biocentre College of Life Sciences University of Dundee UK Keywords glyoxalase lactate methylglyoxal metabolism Trypanosoma brucei trypanothione Correspondence A. H. Fairlamb Division of Biological Chemistry Drug Discovery Wellcome Trust Biocentre College of Life Sciences University of Dundee Dundee DD1 5EH UK Fax 44 1382 38 5542 Tel 44 1382 38 5155 E-mail a.h.fairlamb@dundee.ac.uk Website http www.lifesci.dundee.ac.uk people alan_fairlamb Re-use of this article is permitted in accordance with the Creative Commons Deed Attribution 2.5 which does not permit commercial exploitation Received 16 September 2008 revised 29 October 2008 accepted 6 November 2008 doi 10.1111 j.1742-4658.2008.06788.x The glyoxalase system comprising the metalloenzymes glyoxalase I GLO1 and glyoxalase II GLO2 is an almost universal metabolic pathway involved in the detoxification of the glycolytic byproduct methylglyoxal to D-lactate. In contrast to the situation with the trypanosomatid parasites Leishmania major and Trypanosoma cruzi this trypanothione-dependent pathway is less well understood in the African trypanosome Trypanosoma brucei. Although this organism possesses a functional GLO2 no apparent GLO1 gene could be identified in the T. brucei genome. The absence of GLO1 in T. brucei was confirmed by the lack of GLO1 activity in whole cell extracts failure to detect a GLO1-like protein on immunoblots of cell lysates and lack of D-lactate formation from methylglyoxal as compared to L. major and T. cruzi. T. brucei procyclics were found to be 2.4-fold and 5.7-fold more sensitive to methylglyoxal toxicity than T. cruzi and L. major respectively. T. brucei also proved to be the least adept of the Tritryp parasites in metabolizing methylglyoxal producing L-lactate rather than D-lactate. Restoration .