%0 Journal Article
%T Flux Analysis of the Trypanosoma brucei Glycolysis Based on a Multiobjective-Criteria Bioinformatic Approach
%A Amine Ghozlane
%A Fr¨¦d¨¦ric Bringaud
%A Hayssam Soueidan
%A Isabelle Dutour
%A Fabien Jourdan
%A Patricia Th¨¦bault
%J Advances in Bioinformatics
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/159423
%X Trypanosoma brucei is a protozoan parasite of major of interest in discovering new genes for drug targets. This parasite alternates its life cycle between the mammal host(s) (bloodstream form) and the insect vector (procyclic form), with two divergent glucose metabolism amenable to in vitro culture. While the metabolic network of the bloodstream forms has been well characterized, the flux distribution between the different branches of the glucose metabolic network in the procyclic form has not been addressed so far. We present a computational analysis (called Metaboflux) that exploits the metabolic topology of the procyclic form, and allows the incorporation of multipurpose experimental data to increase the biological relevance of the model. The alternatives resulting from the structural complexity of networks are formulated as an optimization problem solved by a metaheuristic where experimental data are modeled in a multiobjective function. Our results show that the current metabolic model is in agreement with experimental data and confirms the observed high metabolic flexibility of glucose metabolism. In addition, Metaboflux offers a rational explanation for the high flexibility in the ratio between final products from glucose metabolism, thsat is, flux redistribution through the malic enzyme steps. 1. Introduction Trypanosomes are unicellular protozoa that are ubiquitous parasites of higher eukaryotes, including insects, plants, and mammals. Among the numerous species belonging to the trypanosomatid family, Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. are responsible for Human diseases. Most of these parasites live in more than one host over their life cycle and encounter very different environments, such as insect vectors¡¯ gut and vertebrate bloodstream. Consequently, the different parasitic forms have developed distinct morphologies and metabolisms. We will consider here T. brucei, which belongs to the group of parasites responsible for sleeping sickness in Africa. T. brucei belongs to the only group of organisms that performs glycolysis in a peroxisome-like organelle, called glycosome [1]. It is widely considered that this compartmentalized glycolysis requires impermeability of glycosomal membrane to cofactors, such as NAD(P)+ and NAD(P)H, and nucleotides (ATP, ADP, etc.) [2]. As a consequence, the intraglycosomal NAD+/NADH and ATP/ADP balances need to be maintained, which implies that each NAD+ or ATP molecules consumed during the first glycolytic steps have to be regenerated inside the organelle (see Figure 1). Figure 1: Metabolic
%U http://www.hindawi.com/journals/abi/2012/159423/