title: The glyoxalase system of malaria parasites--implications for cell biology and general glyoxalase research.
abstract: Malaria parasites of the genus Plasmodium have developed sophisticated mechanisms to benefit from the nutrient-rich environments of their hosts. For example, by hiding in red blood cells, they found a secure way to tap into the glucose supply of vertebrates. The high-power metabolism of Plasmodium leads not only to a significantly increased glucose consumption of infected erythrocytes, but also to an elevated production of D-lactate from methylglyoxal. The latter substance is a harmful by-product from glycolysis that is detoxified by the ubiquitous glyoxalase system. This system consists of reduced glutathione and two enzymes, the glyoxalases 1 and 2. Inhibition of the glyoxalases in the host/parasite unit is expected to be highly detrimental to the parasite. Moreover, by studying Plasmodium isozymes, physiological functions of the system beyond methylglyoxal conversion became prima facie obvious: (i) the two different active sites of glyoxalase 1 as well as the existence of (insular) glyoxalases in the apicoplast point to alternative substrates and metabolic pathways. (ii) The allostery of glyoxlase 1 and the monomer-dimer equilibrium of glyoxalase 2 suggest novel regulatory features of these enzymes. Here we review the current knowledge on the glyoxalase systems of the host/parasite unit, discuss their potential as drug target and summarize new hypotheses on glyoxalases with respect to general cell biology.
authors.affiliation: Department of Parasitology, Universitätsklinikum Heidelberg, Heidelberg, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Urscher
authors.forename: Romy
authors.initials: R
authors.lastname: Alisch
authors.forename: Marcel
authors.initials: M
authors.lastname: Deponte
mesh_terms: D000818:Animals; D006790:Host-Parasite Interactions; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology*; D010961:Plasmodium / Q000201:enzymology*; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D007527:Isoenzymes; D007791:Lactoylglutathione Lyase; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase