Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzyme histochemical methods were performed on sporozoite infected liver tissue of rats in order to gain insight into the nutrition and metabolism of exoerythrocytic forms of Plasmodium berghei. The following enzymes were demonstrated in the hepatocytic stages of the parasites, obtained 41 and 48 h after inoculation of sporozoites: acid phosphatase, cytochrome oxidase, NADH-tetrazolium reductase, succinate dehydrogenase, NAD+ and NADP+ dependent isocitrate dehydrogenase, NADP+-dependent malate dehydrogenase, lactate dehydrogenases, 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenases and alpha-glycerol-phosphate dehydrogenase. The results suggest that a conventional Embden-Meyerhoff pathway, pentose phosphate pathway and Krebs' citric acid cycle may in part be present in these exoerythrocytic parasites. Alkaline phosphatase, nucleoside polyphosphatase, 5' nucleotidase, glucose-6-phosphatase, alpha-glucan phosphorylase, NAD+ dependent malate dehydrogenase, amino-peptidase M and non-specific esterases were not detected by our techniques in the parasite. The enzyme distribution of this intrahepatocytic malaria parasite revealed by histochemistry is compared with the enzyme distribution in the other phases of the parasite's life cycle.
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PMID:Histochemical observations on the exoerythrocytic malaria parasite Plasmodium berghei in rat liver. 608 94

The effect of concomitant toxoplasma and malaria infection on the reticuloendothelial system was investigated in rats. This was evaluated by the level of plasmodial parasitaemia; humoral antibody response; effect on splenic weight; histopathological changes in thymus and spleen; histopathological and histochemical changes in liver. The parasitaemia appeared after 2 days in single malaria and concomitant infections. The peak was reached after 6 days with single and precedent malaria, and after 10 days with precedent toxoplasma. The clearance of parasitaemia was delayed to 30 days with concomitant infections instead of 14 days with single malaria. Higher than normal malarial antibody levels were reached with precedent toxoplasma, while the toxoplasma antibodies were lower than normal in both concomitant infections. There was a significant increase in splenic weight in both precedent malaria and toxoplasma, followed by a decrease which did not return to normal in case of precedent malaria. The thymus was packed with thymocytes in precedent malaria, while depletion in the cortex occurred in precedent toxoplasma. In the liver, there was glycogen depletion and decrease in succinic dehydrogenase activity in both concomitant infections. Choline esterase activity in precedent malaria was decreased and returned to normal on day 40 while in precedent toxoplasma the activity was normal all through the period. The alkaline phosphatase activity was decreased and returned to normal on day 40 in both concomitant infections.
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PMID:Experimental concomitant toxoplasma and malaria infection in rats. 674 2

Mitochondria of malaria parasites generate a membrane potential through an electron transport system that is a possible target of primaquine and a new anti-malarial drug, atovaquone. However, little information is available for conclusive understanding of the respiratory chain in Plasmodium mitochondria. In the present study, we cloned and characterized from Plasmodium falciparum the genes for the catalytic subunits, SDHA for the flavoprotein (Fp) and SDHB for iron-sulfur protein (Ip), of succinate-ubiquinone oxidoreductase (complex II), which is a marker enzyme for mitochondria and links the TCA cycle and respiratory chain directly. Each of the two genes contains a single open reading frame (ORF), which are located on different chromosomes, 1860 nucleotides on chromosome 10 for SDHA and 963 nucleotides on chromosome 12 for SDHB. The expression of these genes in asynchronous erythrocytic stage cells was confirmed by observation of 3.3 and 2.4 kb transcripts from the SDHA and SDHB genes, respectively. The SDHA and SDHB genes encode proteins of 620 (Fp) and 321 (Ip) amino acids with molecular masses of 69.2 and 37.8 kDa, respectively. A mitochondrial presequence essential for the import of mitochondrial proteins encoded by nuclear DNA, as well as almost all the conserved amino acids indispensable for substrate binding and the catalytic reaction were found in these peptides, indicating the functional importance of this enzyme in the parasite. Interestingly, a P. falciparum-specific insertion and a unicellular organism-specific deletion were found in the amino acid sequence of Fp. This is the first report of the primary structure of the protozoan succinate dehydrogenase.
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PMID:Succinate dehydrogenase in Plasmodium falciparum mitochondria: molecular characterization of the SDHA and SDHB genes for the catalytic subunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits. 1077 96

Mitochondria of the malaria parasite Plasmodium falciparum are morphologically different between the asexual and sexual blood stages (gametocytes). In this paper recent findings of mitochondrial heterogeneity are reviewed based on their ultrastructural characteristics, metabolic activities and the differential expression of their genes in these 2 blood stages of the parasite. The existence of NADH dehydrogenase (complex I), succinate dehydrogenase (complex II), cytochrome c reductase (complex III) and cytochrome c oxidase (complex IV) suggests that the biochemically active electron transport system operates in this parasite. There is also an alternative electron transport branch pathway, including an anaerobic function of complex II. One of the functional roles of the mitochondrion in the parasite is the coordination of pyrimidine biosynthesis, the electron transport system and oxygen utilization via dihydroorotate dehydrogenase and coenzyme Q. Complete sets of genes encoding enzymes of the tricarboxylic acid cycle and the ATP synthase complex are predicted from P. falciparum genomics information. Other metabolic roles of this organelle include membrane potential maintenance, haem and coenzyme Q biosynthesis, and oxidative phosphorylation. Furthermore, the mitochondrion may be a chemotherapeutic target for antimalarial drug development. The antimalarial drug atovaquone targets the mitochondrion.
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PMID:The multiple roles of the mitochondrion of the malarial parasite. 1555 97

Kielmeyera coriacea Mart is a medicinal plant of the Clusiacea (Guttiferae) family used by the native population of Brazil in the treatment of several tropical diseases such as malaria, schistosomiasis, leishmaniasis, and fungal or bacterial infections. Kielmeyera coriacea is also effective as an antidepressant drug. Extracts of the plant are rich in xanthones. Compounds of this class have been reported to inhibit mitochondrial energy metabolism. For this reason the action of the Kielmeyera coriacea extract on hepatic energy metabolism was investigated in the present work, using isolated rat liver mitochondria and the perfused rat liver. In perfused livers the extract (20-80 microg/ml) caused stimulation of oxygen consumption, inhibition of gluconeogenesis and stimulation of glycogenolysis and glycolysis. In isolated mitochondria the Kielmeyera coriacea extract (5-20 microg/ml) stimulated state IV respiration, reduced the ADP/O ratio and decreased the respiratory coefficient. The activities of succinate-oxidase, NADH-oxidase, NADH dehydrogenase and succinate dehydrogenase were inhibited. The ATPase of intact mitochondria was stimulated and the ATPase of uncoupled mitochondria was inhibited. The results of this investigation suggest that the Kielmeyera coriacea extract impairs the hepatic energy metabolism by acting as mitochondrial uncoupler and inhibitor of enzymatic activities linked to the respiratory chain. The impairment of mitochondrial energy metabolism could lead to adverse metabolic effects by the use of the crude extract, but it could equally be the basis of its antiprotozoan and antifungal effects.
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PMID:Effects of the Kielmeyera coriacea extract on energy metabolism in the rat liver. 1624 61

Parasites have exploited unique energy metabolic pathways as adaptations to the natural host habitat. In fact, the respiratory systems of parasites typically show greater diversity in electron transfer pathways than do those of host animals. These unique aspects of parasite mitochondria and related enzymes may represent promising targets for chemotherapy. Natural products have been recognized as a source of the candidates of the specific inhibitors for such parasite respiratory chains. Chalcones was recently evaluated for its antimalarial activity in vitro and in vivo. However, its target is still unclear in malaria parasites. In this study, we investigated that licochalcone A inhibited the bc1 complex (ubiquinol-cytochrome c reductase) as well as complex II (succinate ubiquinone reductase, SQR) of Plasmodium falciparum mitochondria. In particular, licochalcone A inhibits bc1 complex activity at very low concentrations. Because the property of the P. falciparum bc1 complex is different from that of the mammalian host, chalcones would be a promising candidate for a new antimalarial drug.
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PMID:Parasite mitochondria as a target of chemotherapy: inhibitory effect of licochalcone A on the Plasmodium falciparum respiratory chain. 1638 76

In the intraerythrocytic stages of malaria parasites, mitochondria lack obvious cristae and are assumed to derive energy through glycolysis. For understanding of parasite energy metabolism in mammalian hosts, we isolated rodent malaria mitochondria from Plasmodium yoelii yoelii grown in mice. As potential targets for antiplasmodial agents, we characterized two respiratory dehydrogenases, succinate:ubiquinone reductase (complex II) and alternative NADH dehydrogenase (NDH-II), which is absent in mammalian mitochondria. We found that P. y. yoelii complex II was a four-subunit enzyme and that kinetic properties were similar to those of mammalian enzymes, indicating that the Plasmodium complex II is favourable in catalysing the forward reaction of tricarboxylic acid cycle. Notably, Plasmodium complex II showed IC(50) value for atpenin A5 three-order of magnitudes higher than those of mammalian enzymes. Divergence of protist membrane anchor subunits from eukaryotic orthologs likely affects the inhibitor resistance. Kinetic properties and sensitivity to 2-heptyl-4-hydroxyquinoline-N-oxide and aurachin C of NADH: ubiquinone reductase activity of Plasmodium NDH-II were similar to those of plant and fungus enzymes but it can oxidize NADPH and deamino-NADH. Our findings are consistent with the notion that rodent malaria mitochondria are fully capable of oxidative phosphorylation and that these mitochondrial enzymes are potential targets for new antiplasmodials.
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PMID:Mitochondrial dehydrogenases in the aerobic respiratory chain of the rodent malaria parasite Plasmodium yoelii yoelii. 1906 Mar 9

The present study aimed to reveal differences in the activity of a mitochondrial enzyme, succinate dehydrogenase (SDG), in larvae of mosquito Anopheles messeae with various karyotypes. Four-instar larvae of malaria mosquito previously obtained in laboratory conditions from imagoes collected in a taiga population of Tomsk region served as material for the study.
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PMID:[Genetic determination of succinate dehydrogenase activity in Anopheles messeae (diptera, culicidae) larvae]. 1994 42

Malaria is a major worldwide public health threat with worrying social and economic burdens due to the rapid emergence of multidrug-resistant Plasmodium falciparum strains. As a result, there is an urgent need to find novel drugs that might overcome clinical resistance to marketed antimalarials. In recent years, the mitochondrial electron transport chain (mtETC) has been explored for the development of new antimalarials. Type II NADH:quinone oxidoreductase (PfNDH2), succinate dehydrogenase (SDH) and cytochrome bc1 have become a major focus of those efforts, leading to several studies of its biochemistry and the design of potent inhibitors. Furthermore, de novo pyrimidine biosynthesis in malaria parasites, particularly dihydroorotate dehydrogenase (PfDHODH), is also receiving increasing attention. The enzymes involved in the mtETC are valuable targets in malaria chemotherapy, not only because they play a critical role in metabolic pathways of P. falciparum, but also because they differ significantly from the analogous mammalian system. Inhibition of such enzymes results in the shutdown of mitochondrial electron flow, leading to the arrest of pyrimidine biosynthesis and consequent parasite death. In this review, we aim to outline recent advances in the inhibition of mitochondrial metabolic pathways, highlighting the major classes of known inhibitors and those that are currently being developed.
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PMID:Inhibitors of the mitochondrial electron transport chain and de novo pyrimidine biosynthesis as antimalarials: The present status. 2015 68

It is generally accepted that the mitochondria play central roles in energy production of most eukaryotes. In contrast, it has been thought that Plasmodium spp., the causative agent of malaria, rely mainly on cytosolic glycolysis but not mitochondrial oxidative phosphorylation for energy production during blood stages. However, Plasmodium spp. possesses all genes necessary for the tricarboxylic acid (TCA) cycle and most of the genes for electron transport chain (ETC) enzymes. Therefore, it remains elusive whether oxidative phosphorylation is essential for the parasite survival. To elucidate the role of TCA metabolism and ETC in malaria parasites, we deleted the gene for flavoprotein (Fp) subunit, Pbsdha, one of four components of complex II, a catalytic subunit for succinate dehydrogenase activity. The Pbsdha(-) parasite grew normally at blood stages in mouse. In contrast, ookinete formation of Pbsdha(-) parasites in the mosquito stage was severely impaired. Finally, Pbsdha(-) ookinetes failed in oocyst formation, leading to complete malaria transmission blockade. These results suggest that malaria parasite may switch the energy metabolism from glycolysis to oxidative phosphorylation to adapt to the insect vector where glucose is not readily available for ATP production.
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PMID:Critical roles of the mitochondrial complex II in oocyst formation of rodent malaria parasite Plasmodium berghei. 2262 52


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