Characterization of a glycerophosphodiesterase with an unusual tripartite distribution and an important role in the asexual blood stages of Plasmodium falciparum.

Catabolism of glycerophospholipids during the rapid growth of the asexual intraerythrocytic malaria parasite may contribute to membrane recycling and the acquisition of lipid biosynthetic precursors from the host. To better understand the scope of lipid catabolism in Plasmodium falciparum, we have characterized a malarial homolog of bacterial glycerophosphodiesterases. These enzymes catalyze the hydrolysis of glycerophosphodiesterases that are generated by phospholipase-catalyzed removal of the two acyl groups from glycerophospholipids. The P. falciparum glycerophosphodiesterase (PfGDPD) exhibits an unusual tripartite distribution during the asexual blood stage with pools of enzyme in the parasitophorous vacuole, food vacuole and cytosol. Efforts to disrupt the chromosomal PfGDPD coding sequence were unsuccessful, which implies that the enzyme is important for efficient parasite growth. Tagging of the endogenous pool of PfGDPD with a conditional aggregation domain partially perturbed the distribution of the enzyme in the parasitophorous vacuole but had no discernable effect on growth in culture. Kinetic characterization of the hydrolysis of glycerophosphocholine by recombinant PfGDPD, an Mg(2+)-dependent enzyme, yielded steady-state parameters that were comparable to those of a homologous bacterial glycerophosphodiesterase. Together, these results suggest a physiological role for PfGDPD in glycerophospholipid catabolism in multiple subcellular compartments. Possibilities for what this role might be are discussed.