Figure 6.

Model for phosphatidic acid (PA) synthesis in Plasmodium. In the cytoplasm/endoplasmic reticulum (ER), extraplastidial PA synthesis likely takes place in all life cycle stages. Dihydroxyacetone phosphate (DHAP) is converted to glycerol 3-phosphate (G3P) by G3P dehydrogenase (G3PDH), then to lysophosphatidic acid (LPA) by G3P acyltransferase (G3PAT) and finally to PA by LPAAT. In the apicoplast, enzymes involved in plastidial PA synthesis (apiG3PDH and apiG3PAT) are active only during liver stage development. DHAP is transported across the four apicoplast membranes by the triose phosphate transporters (TPT). No exclusive apiLPAAT appears to be present in the Plasmodium genome and we hypothesize that apicoplast-generated LPA could leave the plastid, is acted on by extraplastidial LPAAT in the cytosol/ER (possibly PY016768 or PY02486) to form PA in the cytosol/ER, which is then converted to phospholipids. These phospholipids could then become incorporated into the four membranes of the replicating liver stage apicoplast. Liver stage-expressed enzymes of type II fatty acid synthesis (FAS II) produce the fatty acyl acyl carrier protein (ACP) moiety, which is used by apiG3PAT to produce LPA. Extraplastidial G3PAT and LPAAT use fatty acyl coenzyme A (CoA) moieties. TPT is shown in green, the apicoplast-targeted enzymes in orange and the cytosol/ER enzymes in purple. Enzymes/transporters are in blue text.