Characterization of coproporphyrinogen III oxidase in Plasmodium falciparum cytosol

Nagaraj, Viswanathan Arun; Dasari, Prasad; Arumugam, Rajavel; Rangarajan, Pundi N.; Padmanaban, Govindarajan

doi:10.1016/j.parint.2009.12.001

Cited by 31 publications

(20 citation statements)

References 32 publications

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“…(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.…”

Section: Distribution Of Different Types Of the Tetrapyrrole Biosynthmentioning

confidence: 99%

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

et al. 2011

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Most photosynthetic eukaryotes synthesize both heme and chlorophyll via a common tetrapyrrole biosynthetic pathway starting from glutamate. This pathway was derived mainly from cyanobacterial predecessor of the plastid and differs from the heme synthesis of the plastid-lacking eukaryotes. Here, we show that the coral-associated alveolate Chromera velia, the closest known photosynthetic relative to Apicomplexa, possesses a tetrapyrrole pathway that is homologous to the unusual pathway of apicomplexan parasites. We also demonstrate that, unlike other eukaryotic phototrophs, Chromera synthesizes chlorophyll from glycine and succinyl-CoA rather than glutamate. Our data shed light on the evolution of the heme biosynthesis in parasitic Apicomplexa and photosynthesis-related biochemical processes in their ancestors.

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Section: Distribution Of Different Types Of the Tetrapyrrole Biosynthmentioning

confidence: 99%

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

et al. 2011

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“…The first enzyme, δ-aminolevulinate synthase ( Pf ALAS) [8], [9], and the last two enzymes, Protoporphyrinogen IX oxidase ( Pf PPO) and Ferrochelatase ( Pf FC) [10], [11] localize to the mitochondrion. The enzymes that catalyze the intermediate steps: ALA dehydratase ( Pf ALAD) [12], [13], Porphobilinogen deaminase ( Pf PBGD) [9], [14], and Uroporphyrinogen III decarboxylase ( Pf UROD) [15] localize to the apicoplast (a chloroplast relic), whereas, the next enzyme Coproporphyrinogen III oxidase ( Pf CPO) is cytosolic [16]. Figure 1 depicts the pathway.…”

Section: Introductionmentioning

confidence: 99%

Malaria Parasite-Synthesized Heme Is Essential in the Mosquito and Liver Stages and Complements Host Heme in the Blood Stages of Infection

et al. 2013

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Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS), and the last enzyme, ferrochelatase (FC), in the heme-biosynthetic pathway of Plasmodium berghei (Pb). The wild-type and knockout (KO) parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-14C] aminolevulinic acid (ALA). We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.

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“…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.…”

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confidence: 99%

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

Sigala

Miura

et al. 2014

Journal of Biological Chemistry

142

161

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Characterization of coproporphyrinogen III oxidase in Plasmodium falciparum cytosol

Cited by 31 publications

References 32 publications

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

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

Malaria Parasite-Synthesized Heme Is Essential in the Mosquito and Liver Stages and Complements Host Heme in the Blood Stages of Infection

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

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