Figure 6.

Model of the Alternative CoA biosynthesis pathways in P. yoelii blood stages. In this graphic model, pantothenate is transported into the parasite by a pantothenate transporter (PAT). The first enzymatic step in CoA biosynthesis is the phosphorylation of pantothenate by a pantothenate kinase (PanK) to form 4′-phosphopantothenate (PPA). Addition of cysteine to 4′-PPA by a Phosphopantothenylcysteine Synthase (PPCS) produces 4′-phospho-N-pantothenolycysteine (PPC). Decarboxylation of PPC by a PPC decarboxylase (PPCDC) produces 4′-phosphopantetheine (PP). Adenylation of PP by Phosphopantetheine Adenylyltransferase (PPAT) produces Dephospho-CoA. The latter is phosphorylated by a Dephospho-CoA Kinase (DPCK) to produce CoA. The other alternative depicted route of CoA biosynthesis from pantetheine has been confirmed in prokaryotes and eukaryotes. Transport of pantetheine could be accomplished by PAT or by another unidentified transporter. Pantetheine can be phosphorylated inside the parasite by PanK (or alternative kinase) to 4′ phosphopantetheine, which is the substrate for PPAT, and thus bypassing the PPCS and PPCDC enzymes.