Sialic acids

Sia; an underclass of nonulosonic acids identified in 1936 as "sialic acid" and independently in 1941 as "neuraminic acid". Both terms are established and encompass neuraminic acid, deoxynonulosonic acid, and their derivates. Sia are often bound to galactose or N-acetylgalactosamine and found at the terminal end of many glycans and glycosphingolipids (Varki et al. 2015).

Sia carry a negatively charged carboxylate and a 3-carbon side chain like glycerol at C‑7-9. The molecules attached to C‑5 vary. A common sialic acid in humans is N-acetylneuramic acid (Neu5Ac). In contrast, N‑glycolylneuramic acid (Neu5Gc) is common in animals but absent in humans. Presence of sialic acid – that is N‑acetylneuramic acid - defines the group of sialylated acidic human milk oligosaccharides; Figure 412-8. Sialic acids not belonging to the nonulosonic acid group also exist (Varki et al. 2015).

Pathogens often express Sia binding proteins. One example is the influenza A virus that binds to Sia in α2‑6 bonds: It uses "hemagglutinin" as Sia‑binding protein and also a sialidase (neuramidase) both involved in virus docking and cell entry. This virus class HxNx gets its name from hemagglutinin and neuramidase (Varki et al. 2015​​​​​​​).

Structure of sialylated human milk oligosaccharides
Figure 412-8 Sialylated human milk oligosaccharides. Based on their building blocks, HMO are classified into three basic categories (Ayechu-Muruzabal et al. 2018). Sialylated or acidic HMO are characterised by the presence of at least one N-acetylneuraminic acid residue (sialic acid, purple diamond) added via alpha-2-3 or alpha-2-6 bonds to galactose (yellow circle) or N-acetylglucosamine (blue square) but not glucose (blue circle). HMO that contain sialic acid and fucose also exist (Thurl et al., 2017). Symbols and coloration according to guidelines (Neelamegham et al., 2019).