Purine Transporters

Quashie, N. B., Dorin-Semblat, D., Bray, P. G., Doerig, C., Ranford-Cartwright, L. C., and de Koning, H. P. (2008). A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum Identification of four purine transport activities in intraerythrocytic parasites. Biochem. J. 411, 287-295. 

Disruption of AdoMet metabolism is a key element also in the action of 5 - [(Z)-5-amino-2-butenyl]methylamino 5 -deoxyadenosine (MDL73811), an AdoMet decarboxylase inhibitor which is a highly effective trypanocide (53). Treatment of trypanosomes with MDL73811 caused a 20-fold increase in the trypanosome AdoMet level after only 1 h of exposure. In comparison, AdoMet levels in cultured mammalian cells rose only 1.5-fold after similar treatment with MDL73811 (48). This analog is rapidly concentrated by trypanosomes through the purine transport system (54). 

Byers, T. L., Casara, P. and Bitonti, A. J. (1992) Uptake of the antitrypanosomal drug 5 -([(Z)-4-amino-2-butenyl]methylamino)-5 -deoxyadenosine (MDL 73811) by the purine transport system of Trypanosoma brucei brucei. Biochem. J. 283, 755-758. 

Molecular cloning studies in Leishmania and trypanosomes have revealed that all known purine transporters in these parasites are members of the ENT family described above. These proteins have 11 predicted transmembrane domains with the NH2- and COOH termini located on the inside and outside of the plasma membrane respectively (Fig. 4), and this topological model has been tested for the human equilibrative nucleoside transporter hENTl. Four Leishmania ENT permeases have been characterized, NTl (represented by two isoforms, NTl.l and NTl.2), NT2, NT3 and NT4, with the majority of the work on jqjj 6,57-59 Jjeing performed using the genes from L. donovani and the... 

A hypothesis for the oxidation of purines in the presence of this enzyme has been elaborated by Bergmann and his colleagues. It postulates that the purine, often in one of its less prevalent tautomeric forms, is adsorbed on the protein, or the riboflavin coenzyme, of the enzyme then hydration occurs under the influence of the electronic field of the enz5rme, and this must involve a group that is not sterically blocked by the enzyme but which is accessible to the electron-transport pathway of the riboflavin moiety. Finally, the secondary alcohol is assumed to be dehydrogenated in this pathway to give a doubly... 

PatU SD, Ngo LY, Glue P, Unadkat JD (1998) Intestinal absorption of ribavirin is preferentially mediated by the Na-l—nucleoside purine (Nl) transporter. Pharm Res 15 950-952... 

The primary conclusion that follows from the effect of base sequence on the efficiency of radical cation migration through duplex DNA is that base pairs cannot be considered in isolation. For example, the effect of placing a T in a sequence of purines depends critically on the nature and number of purines. In this regard, the effect of base sequence on radical cation transport emerges from examination of collective properties of the DNA. This is a clear indication that the charge is delocalized over several base pairs, a conclusion that is supported by extensive quantum calculations. 

Fig.n.2. Human duodenal expression variability of nucleoside, organic cation ion, and anion transporters (unpublished data). Shaded box indicates 25-75% of expression range, the line within the box marks the median, and error bars indicate 10-90% of expression range. ENT2, equilibrative nucleoside transporter CNT1, concentrative pyrimidine nucleoside transporter CNT2, concentrative purine nucleoside transporter ... 

Another important vitamin is folate, which is required for purine and pyrimidine nucleotide synthesis. Since folate and its derivatives are generally lipo-phobic anions, they do not traverse biological membranes via simple diffusion but rather have to be taken up into the cells by specific transport processes... 

Wang, J., et al. Functional and molecular characteristics of Na(+)-dependent nucleoside transporters. Pharm. Res. 1997, 14, 1524-1532. Ritzel, M. W., et al. Recent molecular advances in studies of the concen-trative Na+-dependent nucleoside transporter (CNT) family identification and characterization of novel human and mouse proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system rib). Mol. Membr. Biol. 2001, 18, 65-72. 

Wang, J., et al. Na(+)-dependent purine nucleoside transporter from human kidney cloning and functional... 

Schaner, M. E., et al. Transient expression of a purine-selective nucleoside transporter (SPNTint) in a human cell line (HeLa). Pharm. Res. 1997, 14, 1316-1321. 

Schaner, M. E., et al. Functional characterization of a human purine-selective, Na+-dependent nucleoside transporter (hSPNTl) in a mammalian expression system. J. Pharmacol. Exp. Ther. 1999, 289, 1487-1491. 

Thomsen, A. E., Friedrichsen, G., Sorensen, A. H., Andersen, R., Nielsen, C. U., Brodin, B., Begtrup, M., Frokjaer, S., Steffansen, B., Prodrugs of purine and pyrimidine analogues for the intestinal di/ tripeptide transporter PepTl affinity... 

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