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The glyoxalase pathway ofLeishmania infantumwas kinetically character-ized as a trypanothione-dependent system. Using time course analysis based on parameter fitting with a genetic algorithm, kinetic parameters were estimated for both enzymes, with trypanothione derived substrates. A Kmof 0.253 mmand aVof 0.21lmolÆmin )1 Æmg )1 for glyoxalase I, and a Kmof 0.098 mmand aVof 0.18lmolÆmin )1 Æmg )1 for glyoxalase II, were obtained. | iFEBS Journal Quantitative assessment of the glyoxalase pathway in Leishmania infantum as a therapeutic target by modelling and computer simulation Marta Sousa Silva1 Antonio E. N. Ferreira1 Ana Maria Tomas2 3 Carlos Cordeiro1 and Ana Ponces Freire1 1 Centro de Quimica e Bioquimica Departmento de Quimica e Bioquimica Faculdade de Ciencias da Universidade de Lisboa Portugal 2 ICBAS - Instituto de Ciencias Biomedicas AbelSalazar Universidade do Porto Portugal 3 Instituto de Biologia Molecular e Celular Universidade do Porto Portugal Keywords Leishmania trypanothione methylglyoxal glyoxalase modelling Correspondence C. Cordeiro Centro de Quimica e Bioquimica Departmento de Quimica e Bioquimica Faculdade de Ciencias da Universidade de Lisboa Edificio C8 Lisboa Portugal Fax 351 217500088 Tel 351 217500929 E-mail caac@fc.ul.pt http cqb.fc.ul.pt enzimol Note The mathematical model described here has been submitted to the Online Cellular Systems Modelling Database and can be accessed free of charge at http jjj.biochem. sun.ac.za database silva index.html Received 12 November 2004 revised 21 January 2005 accepted 28 February 2005 doi 10.1111 j.1742-4658.2005.04632.x The glyoxalase pathway of Leishmania infantum was kinetically characterized as a trypanothione-dependent system. Using time course analysis based on parameter fitting with a genetic algorithm kinetic parameters were estimated for both enzymes with trypanothione derived substrates. A Km of 0.253 mM and a V of 0.21 imol-min_1-mg_1 for glyoxalase I and a Km of 0.098 mM and a V of 0.18 imol-min_1-mg_1 for glyoxalase II were obtained. Modelling and computer simulation were used for evaluating the relevance of the glyoxalase pathway as a potential therapeutic target by revealing the importance of critical parameters of this pathway in Leishma-nia infantum. A sensitivity analysis of the pathway was performed using experimentally validated kinetic models and experimentally determined metabolite concentrations and .