Nucleoside equilibrative

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.

Adenosine metabolism (Fig. 12.2) is reviewed in Dunwiddie Masino (2001) and Ribeiro et al. (2002). The phosphorylation of intracellular adenosine to AMP is catalyzed by adenosine kinase. Intracellularly, adenosine can also be deami-nated to inosine by adenosine deaminase. Free intracellular adenosine is normally low. Excess adenosine, which cannot be regenerated to ATP, is extruded to the extracellular space by equilibrative nucleoside transporters (ENTs) in the cell membrane. During electrical stimulation or energy depletion, adenosine is... 

Yao, S. Y., Ng, A. M., Muzyka, W. R. et al. (1997). Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENTl and rENT2) from rat tissues. /. Biol. Chem. 272 (45), 28423-30. 

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 Human duodenal expression variability of nucleoside, organic cation ion, and anion transporters (unpublished data).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],... 

Griffiths, M., et al. Molecular cloning and characterization of a nitrobenzylfhioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem. J. 1997, 328, 739-743. 

Craweord, C. R., et al. Cloning of the human equilibrative, nitrobenzyl-mercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line. J. Biol. Chem. 1998, 273, 5288-5293. 

In contrast to other 2,5-anhydroaldoses (which exhibit mutarota-tion, possibly due to the formation of hemiacetals28), 2,5-anhydro-D-glucose does not show any mutarotation.27 The importance of this compound as a potentially useful precursor to C-nucleosides warrants a reinvestigation of the deamination reaction, and the definitive proof of the structure of the compound. The readily accessible 2,5-anhydro-D-mannose (11) does not possess the cis-disposed side-chains at C-2 and C-5 that would be required of a synthetic precursor to the naturally occurring C-nucleosides, with the exception of a-pyrazomycin (8). The possibility of an inversion of the orientation of the aldehyde group in 11 by equilibration under basic conditions could be considered. 

Immunohistochemical study ND not determined GLUT1 facilitative glucose transporter MCT1 monocarboxylate transporter CRT creatine transporter LAT1 L-type amino acid transporter TAUT taurine transporter ENT equilibrative nucleoside transporter Oatp organic anion-transporting polypeptide PAH p-aminohippuric acid RUI retinal uptake index TR-iBRB rat retinal capillary endothelial cells. 

The transport of amino acids at the BBB differs depending on their chemical class and the dual function of some amino acids as nutrients and neurotransmitters. Essential large neutral amino acids are shuttled into the brain by facilitated transport via the large neutral amino acid transporter (LAT) system [29] and display rapid equilibration between plasma and brain concentrations on a minute time scale. The LAT-system at the BBB shows a much lower Km for its substrates compared to the analogous L-system of peripheral tissues and its mRNA is highly expressed in brain endothelial cells (100-fold abundance compared to other tissues). Cationic amino acids are taken up into the brain by a different facilitative transporter, designated as the y system, which is present on the luminal and abluminal endothelial membrane. In contrast, active Na -dependent transporters for small neutral amino acids (A-system ASC-system) and cationic amino acids (B° system), appear to be confined to the abluminal surface and may be involved in removal of amino acids from brain extracellular fluid [30]. Carrier-mediated BBB transport includes monocarboxylic acids (pyruvate), amines (choline), nucleosides (adenosine), purine bases (adenine), panthotenate, thiamine, and thyroid hormones (T3), with a representative substrate given in parentheses [31]. 

Lee, E.-W., Lai, Y, Zhang, H. and Unadkat, J.D. (2006) Identification of the mitochondrial targeting signal of the human equilibrative nucleoside transporter 1 (hENTl) Implications for interspecies differences in mitochondrial toxicity of fialuridine. The Journal of Biologiccd Chemistry, 281 (24), 16700-16706. 

F]-FLT is not or only marginally incorporated into DNA (<2%) and therefore not a direct measure of proliferation [122]. In vitro studies indicated that [ F]-FLT uptake is closely related to thymidine kinase 1 (TK1) activity and respective protein levels [117,118]. p F]-FLT is therefore considered to reflect TK1 activity and hence, S-phase fraction rather than DNA synthesis. Although being a poor substrate for type 1 equilibrative nucleoside transporters (ENT), cellular uptake of [ F]-FLT is further facilitated by redistribution of nucleoside transporters to the cellular membrane after inhibition of endogenous synthesis of thymidylate (TMP) de novo synthesis of TMP) [125]. However, the detailed uptake mechanism of [ F]-FLT is yet unknown and the influence of membrane transporters and various nucleoside metabolizing enzymes remains to be determined. 

An increase of intracellular adenosine levels can also be achieved by inhibition of nucleoside transport proteins. Mammalian nucleoside transport processes can be classified into two types on the basis of their thermodynamic properties. These classes are the concentrative, Na+-dependent transport processes and the equilibrative, Na+-independent processes. The corresponding transporters are called CNTs (concentrative nucleoside transporters) and ENTs (equilibrative nucleoside transporters) (Pastor-Anglada and Baldwin, 2001). 

Eltzschig HK, Abdulla P, Hoffman E, Hamilton KE, Daniels D, Schonfeld C, Loffler M, Reyes G, Duszenko M, Karhausen J, Robinson A, Westerman KA, Coe IR, Colgan SP (2005) HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. J Exp Med 202(11) 1493—1505... 

It has been shown that allylic azides can be trapped, using either phenylacetylene cycloaddition to the azide, or alkene epoxidation, and that [3,3]-sigmatropic equilibration of the possible allylic azides is generally faster than the trapping reactions 42 Nucleoside-derived azide (46) has been shown to undergo reversible [3,3]-sigmatropic... 

Position of Bond Cleavage PNP (EC 2.U.2.1) from human erythrocytes (homogeneous, purified by formycin B affinity chromatography) as well as from E, coli were allowed to equilibrate a mixture of R-l-[1 0lj]-P, pl Oij, hypoxanthine and inosine at pH 7-00 in 10 mm NMR tubes. The chemical shift differences of the 31p nuclei of the two R-l-P s (13 9 Hz for the human erythrocytic and 13.1 Hz for the E. coli enzyme) as well as of the two P3 resonances (13 9 Hz for erythrocytic and 13-7 Hz for E. coli source) clearly indicated C-0 bond cleavage by these enzymes as well. In addition, no evidence was found over the time course of the NMR measurements (l hr) for purine nucleoside phosphorylase catalyzed exchange of pl o + H2O (solvent) J randomized P. Therefore,... 

The Equilibrium Constant Keq in the direction of nucleoside synthesis had been reported by Kalckar (5.) as approximately 35-50. Equilibration of known initial concentrations of R-l-P,... 

Nucleoside transporters (ENT1 -2, SLC28A CNT1 -3, SLC29A) Equilibrative (ENTs) and... 

Equilibrative-type nucleoside transporters (ENTs) were also characterized in rice451 and Arabidopsis370 in reference to cytokinin nucleoside transport using the yeast system. One of the four rice ENT gene products, OsENT2, mediates the uptake of cytokinin nucleoside as well as that of adenosine451 with higher affinity to iPR... 

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