Plasmodium Lipids: Metabolism and Function

This chapter reviews recent advances in understanding the pathways for membrane biogenesis in Plasmodium, presents new information in this field learned from the available Plasmodium genome sequence and its annotation, and discusses progress in lipid-based antimalarial chemotherapy. It focuses on the pathways of synthesis of phospholipids (PLs) and neutral lipids and their importance in parasite physiology, intracellular localization and trafficking of lipids, and newly identified pharmacological targets. Studies with Plasmodium falciparum parasites grown in vitro or isolated from patients with malaria have revealed profound changes in the membrane composition and structure of surrounding uninfected red blood cells. Glycerolipid metabolism in various organisms initiates with the acylation of glycerol-3-phosphate, which can be produced by the phosphorylation of glycerol by glycerokinase or the reduction of the glycolytic intermediate dihydroxyacetone-3-phosphate by dihydroxyacetone-3-phosphate dehydrogenase. The available P. falciparum genome has revealed the presence of only one putative acyl-CoA diacylglycerol acyltransferase gene named PfDGAT1. This gene encodes a polypeptide with a molecular mass of 78.1 kDa with a broad acyl-CoA specificity, localized to the microsomes. The de novo biosynthetic pathways of phatidylethanolamine (PE) and phosphatidylcholine (PC) initiate with the phosphorylation of ethanolamine and choline, conversion of the phosphoethanolamine and phosphocholine formed into CDP-ethanolamine and CDP-choline, and DAG-dependent acylation of the latter products into PE and PC, respectively. Subcellular fractionation of the malarial parasites remains a difficult task, and cellular localization of the various lipids and mechanisms mediating their intracellular trafficking remains to be elucidated.