The methylerythritol (MEP) pathway in Plasmodium apicoplast. Pyruvate kinase (PK) and triose phosphate isomerase (TPI) catalyse the synthesis of pyruvate (PYR) and glyceraldehyde 3-phosphate (GLY3P), which are the starting materials for the MEP pathway. Seven nuclear-encoded enzymes catalyse this pathway, including DOXS (DOXP synthase), IspC (DOXP reductoisomerase), IspD (2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (YgbP)), IspE (4-(cytidine-5-diphospho)-2-C-methyl-D-erythritol kinase (CMK)), IspF (2C-methyl-D-erythritol 2, 4-cyclodiphosphate synthase (YgbB)), IspG (4-hydroxy-3-methyl-2-(E)-butenyl-4-diphosphate synthase (GcpE)), and IspH (4-hydroxy-3-methyl-2-(E)-butenyl-4- diphosphate reductase/LytB). Substrate and products: PEP: phosphoenolpyruvate; DHAP: dihydroxyacetone phosphate; DOXP: 1-deoxy-d-xylulose 5-phosphate; MEP: 2-(C)-methyl-d-erythritol 4-phosphate; CDP-ME: 4-diphosphocytidyl-2-(C)-methylerythritol; CDP-MEP: 4-diphosphocytidyl-2-(C)-methylerythritol 2-phosphate; MEcPP: 2-(C)-methyl-d-erythritol 2,4-cyclopyro-phosphate; HMBPP: (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; IPP: isopentenyl pyrophosphate; DMAPP: dimethylallyl pyrophosphate. Dxr∗ (the asterisk signifies that it is the rate-limiting enzyme in the pathway). The mechanism of transport of IPP and DMAPP is unknown. Mamudu CO, Tebamifor ME, Sule MO, Dokunmu TM, Ogunlana OO, Iheagwam FN. Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Plasmodium falciparum Parasites. Adv Pharmacol Pharm Sci. 2024 10;2024:9940468. PMID: 38765186