Several aspects of purine metabolism were studied in peripheral blood mononuclear cells and fibroblasts from a patient with purine nucleoside phosphorylase deficiency and compared to cells from normal controls. Intact cells were incubated with radioactive purine bases and all purine metabolites were extracted and analyzed. Incubation of purine nucleoside phosphorylase-deficient cells with [3H]h...

Nucleoside transporters (NT) facilitate the movement of nucleosides and nucleobases across cell membranes. NT-mediated transport is vital for the synthesis of nucleic acids in cells that lack de novo purine synthesis. Some nucleosides display biological activity and act as signalling molecules. For example, adenosine exerts a potent action on many physiological processes including vasodilatatio...

Nucleoside transporters (NTs) comprise 2 widely expressed families, the equilibrative nucleoside transporters (diffusion-limited channels) and concentrative nucleoside transporters (sodium-dependent transporters). Because of their anatomic position at the blood-tissue interface, vascular NTs are in an ideal position to influence vascular nucleoside levels, particularly adenosine, which among ot...

Tsx is a nucleoside-specific outer membrane (OM) transporter of Gram-negative bacteria. We present crystal structures of Escherichia coli Tsx in the absence and presence of nucleosides. These structures provide a mechanism for nucleoside transport across the bacterial OM. Tsx forms a monomeric, 12-stranded beta-barrel with a long and narrow channel spanning the outer membrane. The channel, whic...

Extracellular ATP mediates proinflammatory and antiproliferative effects via activation of P2 nucleotide receptors. In contrast, its metabolite, the nucleoside adenosine, is strongly immunosuppressive enhances tumor proliferation metastasis. The conversion to adenosine catalyzed by ectonucleotidases, which are expressed on immune cells typically upregulated cells. present study, we identified s...

In the central nervous system, HIV-1 has a defined tropism for brain macrophages and microglia. Nucleoside analog drugs such as zidovudine improve the clinical and neuropsychological functions in HIV-demented patients. Multiple carrier-mediated transport systems can play an important role in the membrane permeation of nucleosides and nucleoside analog drugs in a number of cells. The purpose of ...

D-Nucleoside analogs, which are in the natural configuration, as well as the L-nucleoside analogs, are clinically relevant antiviral and anticancer agents. Metabolism of L-nucleoside analog diphosphates to the triphosphates, however, remains unexplored. Studies with recombinant nm23-H1 and -H2 isoforms indicated that L-nucleoside analog diphosphates were not phosphorylated by their nucleoside d...

To evaluate the possibility of introducing azole nucleosides as building blocks for metal-mediated base pairs in artificial oligonucleotides, imidazole nucleoside, 1,2,4-triazole nucleoside and tetrazole nucleoside have been synthesized and characterized. The X-ray crystal structures of p-toluoyl-protected 1,2,4-triazole and tetrazole nucleosides are reported. Contrary to the situation primaril...

Concentrative nucleoside transporters (CNTs) are responsible for cellular entry of nucleosides, which serve as precursors to nucleic acids and act as signaling molecules. CNTs also play a crucial role in the uptake of nucleoside-derived drugs, including anticancer and antiviral agents. Understanding how CNTs recognize and import their substrates could not only lead to a better understanding of ...

S. Masino and D. Boison (eds.), Adenosine: A Key Link between Metabolism and Brain Activity, DOI 10.1007/978-1-4614-3903-5_29, © Springer Science+Business Media New York 2013 Abstract Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in...