title: Plasmodium falciparum possesses organelle-specific alpha-keto acid dehydrogenase complexes and lipoylation pathways.
abstract: The human malaria parasite Plasmodium falciparum possesses a single mitochondrion and a plastid-like organelle called the apicoplast. Both organelles contain members of the KADH (alpha-keto acid dehydrogenase) complexes--multienzyme complexes that are involved in intermediate metabolism. In the asexual blood stage forms of the parasites, the alpha-ketoglutarate dehydrogenase and branched chain KADH complexes are both located in the mitochondrion, whereas the pyruvate dehydrogenase is exclusively found in the apicoplast. In agreement with this distribution, Plasmodium parasites have two separate and organelle-specific pathways that guarantee lipoylation of the KADH complexes in both organelles. A biosynthetic pathway comprised of lipoic acid synthase and lipoyl (octanoyl)-ACP:protein Nepsilon-lipoyltransferase B is present in the apicoplast, whereas the mitochondrion is supplied with exogenous lipoic acid, and ligation of the metabolite to the KADH complexes is accomplished by a lipoate protein ligase A similar to that of bacteria and plants. Both pathways are excellent potential targets for the design of new antimalarial drugs.
authors.affiliation: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Günther
authors.forename: P J
authors.initials: PJ
authors.lastname: McMillan
authors.forename: L J M
authors.initials: LJ
authors.lastname: Wallace
authors.forename: S
authors.initials: S
authors.lastname: Müller
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D015388:Organelles / Q000201:enzymology; D010963:Plasmodium falciparum / Q000201:enzymology*; D008063:Thioctic Acid / Q000378:metabolism*
chemical_list: D008063:Thioctic Acid; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)