Fig. 7.

Proposed role of TgACS and acetyl-CoA in the lipid biosynthetic pathway of T. gondii tachyzoite. Acetyl-CoA can be generated by the cytosolic ACS using acetate as a substrate. This pool of acetyl-CoA is used as a substrate for the parasite elongases (ELO1, 2, 3) in the ER to form C18:0, C18:1, C20:0, C20:1, C22:0, and C24:0. These elongated FAs are used to generate phospholipids for the bulk lipid biosynthetic pathways along with the FASII-derived FA and lipid precursor (LPA) made in the apicoplast and the FAs and lipids scavenged from the host. The origin of acetate used by ACS partially derives from metabolized glucose, while another fraction is likely scavenged from the host environment. Acetyl-CoA can also be generated via cytosolic ACL, which uses citrate made by the mitochondrial TCA cycle, and that is exported into the cytosol. This pool of acetyl-CoA can most likely be used by the elongation pathway as a possible redundant route to ACS function in elongation. FAs generated by the apicoplast FASII are the major substrates for the ER elongases. Acetyl-CoA is also made from glycolitic intermediates phosphoenol pyruvate (PEP) and pyruvate by the apicoplast PDH and the mitochondrial BCKDH for the FASII pathway and the mitochondrial TCA cycle, respectively. Theoretically, acetyl-CoA generated by ACS and ACL could fuel the cytosolic FASI pathway but our current results suggest that this is not the case during tachyzoite life stages. APT, apicoplast phosphate transporter, ATS1, apicoplast glycerol-3phosphate acyltransferase; ELO, elongase; Glu, glucose; GT1, glucose transporter; PV, parasitophorous vacuole.