Protoporphyrinogen IX oxidase from Plasmodium falciparum is anaerobic and is localized to the mitochondrion

Tetrapyrrole Synthesis of Photosynthetic Chromerids Is Likely Homologous to the Unusual Pathway of Apicomplexan Parasites

“…(3) Tetrapyrrole pathway of C. velia with putative localizations based on in silico predictions using SignalP and TargetP, respectively (Emanuelsson et al, 2007). (4) Heme biosynthesis of Apicomplexa; localization differs between P. falciparum and Toxoplasma gondii (Sato et al, 2004;Nagaraj et al, 2009aNagaraj et al, , 2009bNagaraj et al, , 2010aNagaraj et al, , 2010bvan Dooren et al, 2006;Wu, 2006;Shanmugam et al, 2010). Numbers of the individual steps of the synthesis represent the enzymes: 1, ALAS; 1a, GTR; 1b, GSA-AT; 2, ALAD; 3, PBGD; 4, UROS; 5, UROD; 6, CPOX; 7, PPOX; 8, FeCH.…”

“…ALA produced in the mitochondrion by the C4 pathway is exported to the apicoplast, where the next three to four steps take place. The sixth enzymatic reaction is situated in the cytosol, while the final two steps are catalyzed in the mitochondrion (Nagaraj et al, 2010a) ( Figure 3B). The apicomplexan pathway is an evolutionary mosaic combining pathways from both heterotrophic and photosynthetic eukaryotes.…”

The Heme Biosynthesis Pathway Is Essential for Plasmodium falciparum Development in Mosquito Stage but Not in Blood Stages

“…In Apicomplexans, 5-aminolevulinic acid (5-ALA) is exclusively synthesized in the mitochondria by the Shemin pathway and not by the C5 pathway. In P. falciparum, a total of eight enzymes in this pathway are located in three different compartments as follows: the mitochondrion (three enzymes) (17)(18)(19), the cytoplasm (one enzyme) (20), and the apicoplast (four enzymes) (21)(22)(23). ALAS is the first enzyme of the pathway, and in many organisms its activity is rate-limiting FIGURE 1.…”

Apicoplast Biosynthetic Pathways as Possible Targets for Combination Therapy of Malaria

“…Recently, the localization of coproporphyrinogen oxidase (Hem F) and protoporphorinogen oxidase IX (Hem G), which, for some time remained a mystery in this pathway, has been discovered by enzyme bioassay and immunoflorecence microscopy [78,79]. The results of these studies have proved Hem F is localized in cytosol and Hem G is localized in mitochondrion.…”

“…6), a well known inhibitor of electron transport chain (ETC)-dependent enzyme dihydroorotate dehydrogenase, was tested against this enzyme. The results showed that it could inhibit the growth of P. falciparum in culture [78]. The combination of atovaqone with proguanil (malarone) is currently in use in some parts of the world to reverse resistance against proguanil.…”