A low-affinity nucleobase transporter in the protozoan parasite Giardia intestinalis

Ey, Peter L.; Davey, Robert A.; Duffield, G. A.

doi:10.1016/0005-2736(92)90081-v

Cited by 13 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). Uridine is probably imported by the thymidine transporter (62,89) and broken down into uracil by a hydrolase (13) or phosphorylase (181). Cytidine and uridine can also be imported by a broad-specificity transporter (63), but most cytidine probably enters the synthetic pathway for UTP synthesis rather than being converted more directly to CTP (Fig.…”

Section: Purine and Pyrimidine Salvagementioning

confidence: 99%

See 1 more Smart Citation

Biology ofGiardia lamblia

2001

View full text Add to dashboard Cite

Giardia lamblia is a common cause of diarrhea in humans and other mammals throughout the world. It can be distinguished from other Giardia species by light or electron microscopy. The two major genotypes of G. lamblia that infect humans are so different genetically and biologically that they may warrant separate species or subspecies designations. Trophozoites have nuclei and a well-developed cytoskeleton but lack mitochondria, peroxisomes, and the components of oxidative phosphorylation. They have an endomembrane system with at least some characteristics of the Golgi complex and encoplasmic reticulum, which becomes more extensive in encysting organisms. The primitive nature of the organelles and metabolism, as well as small-subunit rRNA phylogeny, has led to the proposal that Giardia spp. are among the most primitive eukaryotes. G. lamblia probably has a ploidy of 4 and a genome size of approximately 10 to 12 Mb divided among five chromosomes. Most genes have short 5′ and 3′ untranslated regions and promoter regions that are near the initiation codon. Trophozoites exhibit antigenic variation of an extensive repertoire of cysteine-rich variant-specific surface proteins. Expression is allele specific, and changes in expression from one vsp gene to another have not been associated with sequence alterations or gene rearrangements. The Giardia genome project promises to greatly increase our understanding of this interesting and enigmatic organism

show abstract

Section: Purine and Pyrimidine Salvagementioning

confidence: 99%

“…The majority of CTP is probably generated from UTP by CTP synthetase (151). A low-affinity nucleobase transporter has also been documented (89). Although the transporter's function has not been determined, it may be involved in export of unusable (e.g., thymine) or excessive quantities of nucleobases.…”

Section: Purine and Pyrimidine Salvagementioning

confidence: 99%

Biology ofGiardia lamblia

2001

View full text Add to dashboard Cite

show abstract

“…Wang & Aldritt, 1983;Aldritt & Wang, 1986) and pyrimidine ribonucleotides (Aldritt et al, 1985; for review see Jarroll et al, 1989). Moreover, a low-affinity transporter for purine nucleobases has been described as a potential adenine and guanine donor for the second salvage pathway (Ey et al, 1992). In Crithidia, Leishmania or Trypanosoma, the function of NH is central in salvaging purine nucleosides from the host and essential since the parasites lack purine de novo synthesis (Parkin et al, 1991;Parkin, 1996;Shi et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Giardia lamblia WB C6 clone resistant to the isoflavone formononetin

et al. 2007

View full text Add to dashboard Cite

“…Tritrichomonas foetus has a pyrimidine nucleobase transporter but can also transport xanthine (Hedstorm and Wang, 1989). Giardia intestinalis has a facilitative transporter specific for uracil/thymine, but not cytosine derivatives (Ey et al, 1992). Leishmania major and L. mexicana have a highly selective, high-affinity uracil transporter which also transports 5-fluorouracil as well as the nucleosides uridine, adenosine, and 5-fluoro-2′-deoxyuridine (Papageorgiou et al, 2004; Alzahrani et al, 2016a).…”

Section: Transport Of Pyrimidinesmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

A low-affinity nucleobase transporter in the protozoan parasite Giardia intestinalis

Cited by 13 publications

References 23 publications

Biology ofGiardia lamblia

Biology ofGiardia lamblia

Characterization of a Giardia lamblia WB C6 clone resistant to the isoflavone formononetin

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

Contact Info

Product

Resources

About