Nucleoside concentrative

The less basic purines generate different adducts. Both a C-8 adduct 107 and an 0-6 adduct 108 are produced in the presence of I, while the exclusive product of the reaction of A with 75n and 75o is the unique benzene imine 109. ° These purines also exhibit lower selectivity for trapping of the nitre-nium ions (Table 3). The pyrimidine nucleosides thymidine (T), uridine (U), and cytosine (C) showed negligible reactivity with these two nitrenium ions. ° The selectivity ratios for T, U, and C given in Table 3 are upper limits based on the decrease in the yield of the hydrolysis products at high nucleoside concentration (ca. 50mM). ° Since no adducts were isolated it is not clear that these selectivities represent nucleophilic trapping by the pyrimidines. 

In addition to these transporters, specific transporters for hexoses (GLUT-1), amino acids (EAATl-3, LATl), and nucleosides (concentrative nucleoside transporters - CNT (SLC28 family) and equilibrative nucleoside transporters - ENT (SLC29 family) were reported as being present at the BBB. 

Roth S, Osinski JV, Park SS, Ostwald P, Moshfeghi AA. 1996. Measurement of purine nucleoside concentration in the intact rat retina. J Neurosci Methods 68 87-90. 

The overall uptake of guanosine and the fate of the label in S and cells at different nucleoside concentrations are shown in Figure 1 and Table I respectively. 

Decitabine (5-aza-deoxycytosine) is an analog of the nucleoside 2 -deoxycytidine. It is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and by inhibition of the enzyme DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. DNA hypomethylation is achieved at concentrations below those required to significantly inhibit DNA synthesis, which may promote restoration of function to genes associated with control of cellular differentiation and proliferation. Cytotoxicity in rapidly dividing cells may also result from covalent adducts between DNA methyltransferase and decitabine. 

This method was applied to the determination of these oxidized nucleosides in salmon testes using [ Cio, N5]-8-hydroxy-2 -deoxyguanosine (L-8-OH-dG) as the internal standard (Figure 5.65). Four of the oxidized products were below the limits of detection of the method, while the concentration of 8-OH-dG was determined to be 0.93 ppb. 

Aymerich I, Duflot S, Fernandez-Veledo S, Guillen-Gomez E, Huber-Ruano I, Casado FJ, et al. The concentrative nucleoside transporter family (SLC28) new roles beyond salvage Biochem Soc Trans 2005 33 216-9. 

Brew BJ, Tisch S et al (2003) Lactate concentrations distinguish between nucleoside neuropathy and HIV neuropathy. AIDS 17(7) 1094-1096... 

AUC, area under the time-concentration curve ARV, antiretroviral AV, atrioventricular Cmax, maximum concentration CrCI, creatinine clearance ESRD, end-stage renal disease Cl, gastrointestinal HD, hemodialysis LFT, liver function test NRTI, nucleoside reverse transcriptase inhibitor UCT, uridine diphosphate-glucuronsyltransferase. 

Figure 12.2 Adenosine metabolism. Intracellular adenosine concentrations depend on the balance between energy storage and breakdown. The most important enzymes catalyzing the reactions are indicated. SAH, S-adenosyl-homocysteine ENTs equilibrative nucleoside transporters CNTs, concentrating nucleoside transporters.

Handschuh and Orgel (1973) studied the mineral struvite. It can be precipitated from ocean water in the presence of phosphate if the concentration of NH ions in the water is greater than 0.01 M. If struvite is heated with urea, magnesium pyrophosphate is obtained in a yield of about 20% after 10 days at 338 K if nucleosides are added to the reaction mixture described above, nucleoside diphosphates such as uridine-5 -diphosphate and diuridine-5 -diphosphate are formed in good yields. 

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 ... 

Nucleoside analogues are widely used for the treatment of cancers and viral infections. Although there have been considerable advances in the development of new nucleoside analogs, little is known about the transport mechanisms involved in the intestinal absorption of these compounds. Nucleoside transporters have been subdivided into two major classes by Na+-independent equilibrative transporters (ENT family) and Na+-dependent concentrative transporters (CNT family) [77,100-103],... 

Li, J. Y., R. J. Boado, and W. M. Pardridge. Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. J. Cereb. Blood Flow Metab. 2001, 21, 929-936. 

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