Comparison of the phosphofructokinase and pyruvate kinase activities of Cryptosporidium parvum, Eimeria tenella and Toxoplasma gondii

Denton, Helen; Brown, Samantha M.A.; Roberts, Craig W.; Alexander, James; McDonald, Vincent; Thong, Kam-Wah; Coombs, Graham H.

doi:10.1016/0166-6851(95)02527-8

Cited by 65 publications

(38 citation statements)

References 19 publications

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“…The use of PP i instead of ATP in the phosphorylation of fructose-6-phosphate probably increases the efficiency of glycolysis and can be of importance to organisms which lack electron transport-linked phosphorylation and rely on glycolysis as a major source of energy (Wood 1977;Mertens 1991Mertens , 1993. This is the case for most amitochondriate (Müller 1988;Mertens 1993) and some mitochondriate (Peng and Mansour 1992;Denton et al 1994Denton et al , 1996 protists and probably for green plants under anaerobic conditions (Mertens 1991).…”

mentioning

confidence: 99%

The Pyrophosphate-Dependent Phosphofructokinase of the Protist, Trichomonas vaginalis, and the Evolutionary Relationships of Protist Phosphofructokinases

et al. 1998

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The pyrophosphate-dependent phosphofructokinase (PPi-PFK) of the amitochondriate protist Trichomonas vaginalis has been purified. The enzyme is a homotetramer of about 50 kDa subunits and is not subject to allosteric regulation. The protein was fragmented and a number of peptides were sequenced. Based on this information a PCR product was obtained from T. vaginalis gDNA and used to isolate corresponding cDNA and gDNA clones. Southern analysis indicated the presence of five genes. One open reading frame (ORF) was completely sequenced and for two others the 5' half of the gene was determined. The sequences were highly similar. The complete ORF corresponded to a polypeptide of about 46 kDa. All the peptide sequences obtained were present in the derived sequences. The complete ORF was highly similar to that of other PFKs, primarily in its amino-terminal half. The T. vaginalis enzyme was most similar to PPi-PFK of the mitochondriate heterolobosean, Naegleria fowleri. Most of the residues shown or assumed to be involved in substrate binding in other PPi-PFKs were conserved in the T. vaginalis enzyme. Direct comparison and phylogenetic reconstruction revealed a significant divergence among PPi-PFKs and related enzymes, which can be assigned to at least four distantly related groups, three of which contain enzymes of protists. The separation of these groups is supported with a high percentage of bootstrap proportions. The short T. vaginalis PFK shares a most recent common ancestor with the enzyme from N. fowleri. This pair is clearly separated from a group comprising the long (>60-kDa) enzymes from Giardia lamblia, Entamoeba histolytica pfk2, the spirochaetes Borrelia burgdorferi and Trepomena pallidum, as well as the alpha- and beta-subunits of plant PPi-PFKs. The third group ("X") containing protist sequences includes the glycosomal ATP-PFK of Trypanosoma brucei, E. histolytica pfk1, and a second sequence from B. burgdorferi. The fourth group ("Y") comprises cyanobacterial and high-G + C, Gram-positive eubacterial sequences. The well-studied PPi-PFK of Propionibacterium freudenreichii is highly divergent and cannot be assigned to any of these groups. These four groups are well separated from typical ATP-PFKs, the phylogenetic analysis of which confirmed relationships established earlier. These findings indicate a complex history of a key step of glycolysis in protists with several early gene duplications and possible horizontal gene transfers.

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mentioning

confidence: 99%

The Pyrophosphate-Dependent Phosphofructokinase of the Protist, Trichomonas vaginalis, and the Evolutionary Relationships of Protist Phosphofructokinases

et al. 1998

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“…The only enzyme absent in the GenBank C. parvum contigs at the moment is the aldolase. In contrast to P. falciparum, but in agreement with early observations that C. parvum lacks an active tricarboxylic acid (Krebs') cycle (Denton et al, 1996;Entrala and Mascaro, 1997), no enzymes within the Krebs' cycle could be identified from all available C. parvum genomic data.…”

Section: Energy Metabolismsupporting

confidence: 81%

“…Early biochemical analyses indicated that C. parvum relies mainly on glycolysis as an energy source (Denton et al, 1996;Entrala and Mascaro, 1997). A great number of enzymatic activities within the pathway have been detected in oocysts and free sporozoites, almost all of which were present in the cytosol.…”

Section: Energy Metabolismmentioning

confidence: 99%

Cryptosproridium Parvum Genomics: Impact on Research and Control

Zhu

Abrahamsen

World Class Parasites

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Cryptosporidium parvum is a well-recognized cause of diarrhea in humans and animals throughout the world, and is associated with a substantial degree of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Despite intensive efforts over the past 20 years, there is currently no effective therapy for treating or preventing infection by C. parvum. Until recently, the development of effective anticryptosporidial therapies has been hindered by the paucity of biological targets for structurebased drug design. With the pending completion of sequencing of the entire C. parvum genome, there should be no lack of potential biological targets for development of specific inhibitors. What are needed are focused efforts to identify essential parasite biochemical pathways for which specific inhibitors can be developed that are safe to the host. Analysis of the currently available sequences has identified specific aspects of C. parvum biochemistry that are unique relative to mammals. In addition, the ongoing genome efforts are providing a clearer picture of the biology of the apicomplexan parasites. It is becoming evident that C. parvum uses distinct approaches to solve basic metabolic needs as compared to Plasmodium falciparum and Toxoplasma gondii. These differences suggest that therapies developed for these model apicomplexans may not necessarily be effective against cryptosporidiosis, and emphasizes the importance of understanding the unique biology of C. parvum.

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“…Moreover, the distribution of these compounds is generally similar to that found in the T. gondii extract. C. parvum oocysts have also been shown to have a pyrophosphate dependent metabolism (33,34), possessing a PPi-PFK similar to that described for T. gondii (33) and Eimeria tenella (33), but other aspects of polyphosphate metabolism or storage have not yet been described. Nevertheless, the fact that the C. parvum spectrum showed clear evidence of condensed phosphate species naturally suggested the possibility that that this organism might also have these phosphates present in a solid-state form and might therefore be particularly susceptible to growth inhibition by bisphosphonate inhibitors of the enzyme farnesyl pyrophosphate synthase, which are used extensively in bone resorption therapy.…”

Section: Resultsmentioning

confidence: 95%

“…In T. brucei, T. cruzi and L. major, we also showed that these molecules are localized to the parasite's acidocalcisomes, and that they are present as solid-like complexes with calcium and magnesium (31) and also have an average chain length of 3.3 phosphates per molecule. T. gondii tachyzoites also contain acidocalcisomes and a V-H ϩ -PPase (4, 7) and T. gondii is known to utilize pyrophosphate in place of ATP as an energy donor by the action of a pyrophosphate dependent phosphofructokinase (PPi-PFK) (32,33). These results suggest that condensed phosphates in T. gondii may play a role as both counter-ions for high levels of divalent cations within the parasite's acidocalcisomes, in addition to being active substrates in cellular metabolism.…”

Section: Resultsmentioning

confidence: 99%

31P NMR of Apicomplexans and the Effects of Risedronate on Cryptosporidium parvum Growth

Moreno

Bailey

Luo

et al. 2001

Biochemical and Biophysical Research Communications

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Comparison of the phosphofructokinase and pyruvate kinase activities of Cryptosporidium parvum, Eimeria tenella and Toxoplasma gondii

Cited by 65 publications

References 19 publications

The Pyrophosphate-Dependent Phosphofructokinase of the Protist, Trichomonas vaginalis, and the Evolutionary Relationships of Protist Phosphofructokinases

The Pyrophosphate-Dependent Phosphofructokinase of the Protist, Trichomonas vaginalis, and the Evolutionary Relationships of Protist Phosphofructokinases

Cryptosproridium Parvum Genomics: Impact on Research and Control

31P NMR of Apicomplexans and the Effects of Risedronate on Cryptosporidium parvum Growth

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