Metabolic maps and functions of the Plasmodium falciparum apicoplast

Identification of apicoplast-targeted proteins Proteins that function in the apicoplast must be targeted back to the organelle, which is accomplished by means of a bipartite leader sequence. Bioinformatic tools and their use to find the complement of apicoplast proteins are described. Apicoplast function The apicoplast is indispensable for parasite replication and continued infection of host cells. Investigating proteins that are produced by, or function in, the apicoplast could generate answers to the questions surrounding the function of the apicoplast. Apicoplast metabolic networks The networks of pathways in the apicoplast have been reconstructed using bioinformatics and comparisons with plant and bacterial metabolic pathways. Many of the pathways that have been detected are involved in lipid or lipid-related functions, which might reveal apicoplast-specific functions that make this plastid essential. Carbon and energy requirements The apicoplast is non-photosynthetic, so how does it obtain energy, reducing powew and components, particularly carbon, for anabolic syntheses? Possible pathways based on reconstructed metabolic networks are reviewed. Isopentenyl diphosphate synthesis A complete virtual pathway of plastid isoprenoid synthesis has been assembled which provides a starting point for future biochemical verification. This pathway is important for synthesis of prosthetic groups. Fatty-acid synthesis The dogma that parasites lack de novo fatty-acid synthesis has been challenged by the discovery and characterization of several Plasmodium falciparum fatty-acid-synthesis enzymes. A complete biosynthetic pathway for lipids in the apicoplast is described. Haem biosynthesis How does the malaria parasite, an organism with a plastid but no ability to synthesize chlorophyll, obtain haem? The authors reconstruct pathways to haem biosynthesis and speculate that the apicoplast and the mitochondrion, which co-localize in the parasite cell, exhange substrates to produce haem.