Discovery of novel monosaccharides in animal glycans: natural occurrence of N‐glycolylhexosamines (607.6)

Abstract

Metabolism of the major mammalian sialic acid N‐glycolylneuraminic acid (Neu5Gc) generates N‐glycolylglucosamine (GlcNGc) as a byproduct of its degradative pathway (1). Mammalian cells cultured with exogenous chemically synthesized GlcNGc were found to synthesize UDP‐GlcNGc (2). Chemically synthesized N‐glycolylgalactosamine (GalNGc) was also utilized by mammalian cells to synthesize UDP‐GalNGc and UDP‐GlcNGc, and these served as precursors for assembly of most major glycan classes (3). We asked if these novel reactions could also happen naturally. Comparing wild‐type with Neu5Gc‐deficient mice, we demonstrate that Neu5Gc metabolism is indeed a source of naturally‐occurring UDP‐GalNGc and UDP‐GlcNGc. These endogenously derived N‐glycolylated aminosugars are also naturally incorporated into animal glycans such as chondroitin sulfates (CS), O‐glycans, and N‐glycans. In contrast, humans lack Neu5Gc biosynthesis and should therefore be devoid of GalNGc and GlcNGc in glycans, and also be deficient in any as yet unknown functions these glycans may mediate. Comparisons of human and chimpanzee samples indeed show the predicted difference. However, there is detectable trace amounts of GalNGc in human CS, likely derived from Neu5Gc‐containing animal‐derived foods, particularly of mammalian origin.(1) Bergfeld et al., J Biol Chem. 2012 Aug 17;287(34):28865‐81 (2) Macauley et al., J Biol Chem. 2012 Aug 17;287(34):28882‐97 (3) Bergfeld et al., J Biol Chem. 2012 Aug 17;287(34):28898‐916Grant Funding Source: This work was supported by NIH grant R01 GM32373.