Table of Contents
Molecular Biology International
Volume 2011 (2011), Article ID 135701, 10 pages
http://dx.doi.org/10.4061/2011/135701
Review Article

Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

1Research Unit for Tropical Diseases, de Duve Institute, TROP 74.39, Avenue Hippocrate 74, 1200 Brussels, Belgium
2Department of Chemistry, Heritage Institute of Technology, Chowbaga Road, Anandapur, Kolkata 700107, India
3Laboratory of Experimental Medicine, Université Libre de Bruxelles, Route de Lennik 808, CP 618, 1070 Brussels, Belgium
4Laboratory of Biochemistry, Université Catholique de Louvain, Brussels, Belgium
5Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisas em Energia e Materiais (CNPEM), Caixa Postal 6192, 13083-970 Campinas, SP, Brazil

Received 9 December 2010; Accepted 20 January 2011

Academic Editor: Hemanta K. Majumder

Copyright © 2011 Shreedhara Gupta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G6PDHs contain a unique 37 amino acid long N-terminal extension that in T. cruzi seems to regulate the enzyme activity in a redox-state-dependent manner. T. brucei and T. cruzi G6PDHs, but not their Leishmania spp. counterpart, are inhibited, in an uncompetitive way, by steroids such as dehydroepiandrosterone and derivatives. The Trypanosoma enzymes are more susceptible to inhibition by these compounds than the human G6PDH. The steroids also effectively kill cultured trypanosomes but not Leishmania and are presently considered as promising leads for the development of new parasite-selective chemotherapeutic agents.