<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bardor, M.</style></author><author><style face="normal" font="default" size="100%">Nguyen, D. H.</style></author><author><style face="normal" font="default" size="100%">Diaz, S.</style></author><author><style face="normal" font="default" size="100%">Ajit Varki</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cells</style></title><secondary-title><style face="normal" font="default" size="100%">J Biol Chem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">The Journal of biological chemistry</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amines/chemistry</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Biological Transport</style></keyword><keyword><style  face="normal" font="default" size="100%">Blotting</style></keyword><keyword><style  face="normal" font="default" size="100%">Caco-2 Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Membrane/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">CHO Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Chromatography</style></keyword><keyword><style  face="normal" font="default" size="100%">Cricetinae</style></keyword><keyword><style  face="normal" font="default" size="100%">Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Cytosol/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Diffusion</style></keyword><keyword><style  face="normal" font="default" size="100%">Endocytos</style></keyword><keyword><style  face="normal" font="default" size="100%">High Pressure Liquid</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Western</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2005</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Feb 11</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/15557321</style></url></web-urls></urls><number><style face="normal" font="default" size="100%">6</style></number><edition><style face="normal" font="default" size="100%">2004/11/24</style></edition><volume><style face="normal" font="default" size="100%">280</style></volume><pages><style face="normal" font="default" size="100%">4228-37</style></pages><isbn><style face="normal" font="default" size="100%">0021-9258 (Print)0021-92</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;N-Glycolylneuraminic acid (Neu5Gc) is a widely expressed sialic acid in mammalian cells. Although humans are genetically deficient in producing Neu5Gc, small amounts are present in human cells in vivo. A dietary origin was suggested by human volunteer studies and by observing that free Neu5Gc is metabolically incorporated into cultured human carcinoma cells by unknown mechanisms. We now show that free Neu5Gc uptake also occurs in other human and mammalian cells. Inhibitors of certain non-clathrin-mediated endocytic pathways reduce Neu5Gc accumulation. Studies with human mutant cells show that the lysosomal sialic acid transporter is required for metabolic incorporation of free Neu5Gc. Incorporation of glycosidically bound Neu5Gc from exogenous glycoconjugates (relevant to human gut epithelial exposure to dietary Neu5Gc) requires the transporter as well as the lysosomal sialidase, which presumably acts to release free Neu5Gc. Thus, exogenous Neu5Gc reaches lysosomes via pinocytic/endocytic pathways and is exported in free form into the cytosol, becoming available for activation and transfer to glycoconjugates. In contrast, N-glycolylmannosamine (ManNGc) apparently traverses the plasma membrane by passive diffusion and becomes available for conversion to Neu5Gc in the cytosol. This mechanism can also explain the metabolic incorporation of chemically synthesized unnatural sialic acids, as reported by others. Finally, to our knowledge, this is the first example of delivery to the cytosol of an extracellular small molecule that cannot cross the plasma membrane, utilizing fluid pinocytosis and a specific lysosomal transporter. The approach could, thus, potentially be generalized to any small molecule that has a specific lysosomal transporter but not a plasma membrane transporter.&lt;/p&gt;</style></abstract><work-type><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov&#039;tResearch Support, U.S. Gov&#039;t, P.H.S.</style></work-type><accession-num><style face="normal" font="default" size="100%">15557321 PMID</style></accession-num><notes><style face="normal" font="default" size="100%">&lt;p&gt;J Biol Chem. 2005 Feb 11;280(6):4228-37. Epub 2004 Nov 22.&lt;/p&gt;&lt;p&gt;&amp;nbsp;&lt;/p&gt;</style></notes><auth-address><style face="normal" font="default" size="100%">Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California, 92093-0687, USA.</style></auth-address></record></records></xml>