Neu5Ac

Neu5Ac, or N-acetylneuraminic acid, is a nine-carbon acidic monosaccharide and the most common member of the sialic acids family. It is typically found as a terminal residue on glycans of vertebrate glycoproteins and glycolipids, often linked by α2-3 or α2-6 glycosidic bonds to galactose or N-acetylgalactosamine.

In humans and other mammals, Neu5Ac is produced de novo in cells and also released from glycoconjugates by sialidases. The biosynthetic pathway starts from UDP-N-acetylglucosamine and proceeds through several steps catalyzed by the enzyme GNE (UDP-GlcNAc 2-epimerase/ManNAc kinase) to generate Neu5Ac, which is activated to CMP-Neu5Ac by CMP-sialic acid synthetase (CMAS). CMP-Neu5Ac serves as the donor for sialyltransferases that incorporate Neu5Ac into glycans. Neu5Ac can also be recycled after cleavage from glycoconjugates by neuraminidases.

Neu5Ac plays multiple roles in biology. Its negative charge at physiological pH contributes to the hydration and steric properties of the glycocalyx, influencing cell–cell and cell–matrix interactions, signaling, and immune recognition. It modulates binding to siglecs, selectins, and other lectins, affecting processes such as development, inflammation, and host–pathogen interactions. Pathogens often exploit sialic acids for attachment and immune evasion; conversely, host organisms deploy sialic acids in defense and regulation. Some bacteria can catabolize Neu5Ac via a Nan pathway involving NanT, NanA, NanK, and NanE to derive energy and carbon.

In humans, Neu5Ac is the predominant sialic acid, with other forms like Neu5Gc absent due to gene loss in CMAH. Neu5Ac is also used in biotechnology and therapeutic glycoengineering as a precursor for sialylated products.