title: Expression of a PTS2-truncated hexokinase produces glucose toxicity in Leishmania donovani.
abstract: Compartmentalization of glycolytic enzymes in glycosomes is vital in trypanosomatid parasites. Retention of these enzymes in the cytosol induces sugar toxicity and accumulation of intermediate metabolites, notably the hexokinase product glucose-6-phosphate. However, the role of hexokinase in sugar mediated toxicity remains unexplored. We have generated Leishmania donovani transfectants expressing a catalytically active cytosolic mutant of hexokinase. In the presence of glucose, these transfectants exhibited toxicity during log and stationary phases of growth. These results suggest that targeting of hexokinase to the glycosome is required to prevent uncontrolled and cytotoxic glucose phosphorylation in L. donovani parasites.
authors.affiliation: Parasitology Division, Central Drug Research Institute, C.S.I.R, Lucknow 226001, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
authors.forename: Rashmi
authors.initials: R
authors.lastname: Srivastava
authors.forename: Amogh A
authors.initials: AA
authors.lastname: Sahasrabuddhe
authors.forename: Chhitar M
authors.initials: CM
authors.lastname: Gupta
mesh_terms: D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000633:toxicity*; D006593:Hexokinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007893:Leishmania donovani / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000074437:Peroxisomal Targeting Signal 2 Receptor; D011485:Protein Binding; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism
chemical_list: D000074437:Peroxisomal Targeting Signal 2 Receptor; D015800:Protozoan Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D006593:Hexokinase; D005947:Glucose