title: Why Is N-Glycolylneuraminic Acid Rare in the Vertebrate Brain?
abstract: The sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) differ by a single oxygen atom and are widely found at the terminal position of glycans on vertebrate cell surfaces. In animals capable of synthesizing Neu5Gc, most tissues and cell types express both sialic acids, in proportions that vary between species. However, it has long been noted that Neu5Gc is consistently expressed at trace to absent levels in the brains of all vertebrates studied to date. Although several reports have claimed to find low levels of Neu5Gc-containing glycans in neural tissue, no study definitively excludes the possibility of contamination with glycans from non-neural cell types. This distribution of a molecule - prominently but variably expressed in extraneural tissues but very low or absent in the brain - is, to our knowledge, unique. The evolutionarily conserved brain-specific suppression of Neu5Gc may indicate that its presence is toxic to this organ; however, no studies to date have directly addressed this very interesting question. Here we provide a historical background to this issue and discuss potential mechanisms causing the suppression of Neu5Gc expression in brain tissue, as well as mechanisms by which Neu5Gc may exert the presumed toxicity. Finally, we discuss future approaches towards understanding the mechanisms and implications of this unusual finding.
authors.affiliation: Glycobiology Research and Training Center, Center for Academic Research and Training in Anthropogeny, Biomedical Sciences Graduate Program, Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, 9500 Gilman Dr., MC 0687, La Jolla, CA, 92093-0687, USA.
authors.forename: Leela R L
authors.initials: LR
authors.lastname: Davies
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006899:Mixed Function Oxygenases / Q000172:deficiency* / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism*; D009438:Neuraminic Acids / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D013045:Species Specificity
chemical_list: D005732:Gangliosides; D009438:Neuraminic Acids; D011134:Polysaccharides; C032592:N-glycolylneuraminic acid; D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase; D019158:N-Acetylneuraminic Acid