Purine and Pyrimidine Transport in Schistosoma mansoni

Levy, Michael G.; Read, Clark P.

doi:10.2307/3279455

Cited by 47 publications

(30 citation statements)

References 9 publications

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“…As shown in Table 1, schistosomes are capable of salvaging pyrimidine nucleobases and nucleosides (Levy and Read, 1975a; Nollen et al, 1976; Mattoccia et al, 1981; Mattoccia and Ciolo, 1983; el Kouni and Naguib, 1990). Thymine, cytosine and orotidine are transported into adult S. mansoni , but not incorporated into their nucleic acids (el Kouni and Naguib, 1990).…”

Section: Uptake Of Pyrimidine Nucleobases and Nucleosidesmentioning

confidence: 99%

“…The second transporter is specific for adenosine. The third transporter has high affinity for adenine but also transports adenosine (Levy and Read, 1975a). Uridine uptake is saturable.…”

Section: Transport Of Pyrimidinesmentioning

confidence: 99%

“…Studies on the biological, chemical and pharmacological aspects of pyrimidine metabolism in various organisms, from prokaryotes to mammalian systems, are numerous and have been discussed in several reviews by O’Donovan and Neuhard (1970), Henderson and Paterson (1973), Levine et al (1974), Jaffe (1975), Hurst (1980), Jones (1980), Kensler and Cooney (1981), Munch-Peterson (1983), Hammond and Gutteriddge (1984), Hassan and Coombs (1988), Evans and Guy (2004), Hyde (2007), Garavito et al (2015), and Krungkrai and Krungkrai (2016). However, in contrast to the relatively extensive work on purine metabolism in schistosomes (Senft et al, 1972, 1973a and 1973b; Stegman et al, 1973; Crabtree and Senft, 1974; Miech et al, 1975; Levy and Read, 1975a and 1975b; Senft and Crabtree, 1983; el Kouni et al, 1983a, 1985, 1987 and 1989; Dovey, et al, 1984 and 1985; el Kouni and Cha, 1987; Baer et al, 1988; el Kouni, 1991; Craig III et al, 1991; Yuan et al, 1993; Kanaaneh et al, 1994: Kanaani et al, 1995 and 1997; Foulk et al, 2002; Pereira et al, 2003, 2005, 2010a and 2010b; da Silveira et al, 2004; Yang et al, 2007; Castilho et al, 2010; D’Muniz-Pereira et al, 2011; Postigo et al, 2010; Marques-Ide et al, 2012; de Moraes et al, 2013; Romanello et al, 2013 and 2017; Saverese and el Kouni, 2014; Torini et al, 2016; Zeraik et al, 2017), little information is available on pyrimidine metabolism in this parasite.…”

Section: Introductionmentioning

confidence: 99%

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Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

Kouni

2017

Comparative Biochemistry and Physiology Part B: Biochemistry an

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Schistosomes are responsible for the parasitic disease schistosomiasis, an acute and chronic parasitic ailment that affects more than 240 million people in 70 countries worldwide. It is the second most devastating parasitic disease after malaria. At least 200,000 deaths per year are associated with the disease. In the absence of the availability of vaccines, chemotherapy is the main stay for combating schistosomiasis. The antischistosomal arsenal is currently limited to a single drug, Praziquantel, which is quite effective with a single-day treatment and virtually no host-toxicity. Recently, however, the question of reduced activity of Praziquantel has been raised. Therefore, the search for alternative antischistosomal drugs merits the study of new approaches of chemotherapy. The rational design of a drug is usually based on biochemical and physiological differences between pathogens and host. Pyrimidine metabolism is an excellent target for such studies. Schistosomes, unlike most of the host tissues, require a very active pyrimidine metabolism for the synthesis of DNA and RNA. This is essential for the production of the enormous numbers of eggs deposited daily by the parasite to which the granulomas response precipitate the pathogenesis of schistosomiasis. Furthermore, there are sufficient differences between corresponding enzymes of pyrimidine metabolism from the host and the parasite that can be exploited to design specific inhibitors or “subversive substrates” for the parasitic enzymes. Specificities of pyrimidine transport also diverge significantly between parasites and their mammalian host. This review deals with studies on pyrimidine metabolism in schistosomes and highlights the unique characteristic of this metabolism that could constitute excellent potential targets for the design of safe and effective antischistosomal drugs. In addition, pyrimidine metabolism in schistosomes is compared with that in other parasites where studies on pyrimidine metabolism have been more elaborate, in the hope of providing leads on how to identify likely chemotherapeutic targets which have not been looked at in schistosomes.

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Section: Uptake Of Pyrimidine Nucleobases and Nucleosidesmentioning

confidence: 99%

“…The second transporter is specific for adenosine. The third transporter has high affinity for adenine but also transports adenosine (Levy and Read, 1975a). Uridine uptake is saturable.…”

Section: Transport Of Pyrimidinesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

Kouni

2017

Comparative Biochemistry and Physiology Part B: Biochemistry an

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“…Their existence was suggested in Clonorchis sinensis, Paragonimus ohirai [10], Mesocestoides corti [2], Schistosoma japonicum [8], S. mansoni [1,12,13], Angiostrongylus cantonensis [18]. The present study suggested that A. costaricensis also possessed a pyrimidine de novo synthetic pathway and salvage pathway.…”

mentioning

confidence: 89%

Effects of Nucleic Acid Inhibitors on the Development of Angiostrongylus costaricensis in Vitro.

Hata

Niimura

Yano

1998

The Journal of Veterinary Medical Science

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ABSTRACT. Nucleic acid biosynthesis of Angiostrongylus costaricensis was examined with various inhibitors; aminopterin (inhibitor of purine and pyrimidine de novo biosynthetic pathways), 8-azaguanine (specific inhibitor of purine salvage pathway) and PALA (specific inhibitor of pyrimidine de novo biosynthetic pathway) were applied in in vitro culture developing from the third stage larvae to young adult in chemically defined medium. It was suggested that A. costaricensis possessed functional purine and pyrimidine de novo biosynthetic pathways and also that they could utilize exogenous sources of purines and pyrimidines by salvage pathways for their development. -KEY WORDS: Angiostrongylus costaricensis, de novo biosynthesis, nucleic acid biosynthesis.

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“…Schistosomes are unable to synthesize purines de novo [16]. The ATP catabolic pathway that is driven by SmATPDase1action in the external environment of the intravascular worms may yield purine derivatives in their vicinity that can then be easily imported from the host bloodstream [17].…”

Section: Introductionmentioning

confidence: 99%

Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP

Da’dara¹,

Bhardwaj²,

Skelly³

2014

Purinergic Signalling

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Schistosomes are parasitic worms that can live in the bloodstream of their vertebrate hosts for many years. It has been proposed that the worms impinge on host purinergic signalling by degrading proinflammatory molecules like ATP as well as prothrombotic mediators like ADP. This capability may help explain the apparent refractoriness of the worms to both immune elimination and thrombus formation. Three distinct ectoenzymes, expressed at the host-exposed surface of the worm's tegument, are proposed to be involved in the catabolism of ATP and ADP. These are alkaline phosphatase (SmAP), phosphodiesterase (SmNPP-5), and ATP diphosphohydrolase (SmATPDase1). It has recently been shown that only one of these enzymes-SmATPDase1-actually degrades exogenous ATP and ADP. However, a second ATP diphosphohydrolase homolog (SmATPDase2) is located in the tegument and has been reported to be released by the worms. It is possible that this enzyme too participates in the cleavage of exogenous nucleotide tri-and di-phosphates. To test this hypothesis, we employed RNA interference (RNAi) to suppress the expression of the schistosome SmATPDase1 and SmATPDase2 genes. We find that only SmATPDase1-suppressed parasites are significantly impaired in their ability to degrade exogenously added ATP or ADP. Suppression of SmATPDase2 does not appreciably affect the worms' ability to catabolize ATP or ADP. Furthermore, we detect no evidence for the secretion or release of an ATP-hydrolyzing activity by cultured parasites. The results confirm the role of tegumental SmATPDase1, but not SmADTPDase2, in the degradation of the exogenous proinflammatory and prothrombotic nucleotides ATP and ADP by live intravascular stages of the parasite.

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Purine and Pyrimidine Transport in Schistosoma mansoni

Cited by 47 publications

References 9 publications

Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

Effects of Nucleic Acid Inhibitors on the Development of Angiostrongylus costaricensis in Vitro.

Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP

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