ManNAc

N-acetylmannosamine (ManNAc) is a naturally occurring amino sugar and an essential intermediate in the biosynthesis of sialic acids, especially N-acetylneuraminic acid (Neu5Ac). It is the N-acetylated derivative of the monosaccharide mannose, in which the amino group at carbon-2 bears an acetyl substituent.

In vertebrates, sialic acid biosynthesis begins from UDP-GlcNAc and proceeds through ManNAc and its phosphorylated form. The human enzyme GNE (UDP-GlcNAc 2-epimerase/N-acetylmannosamine kinase) catalyzes the first two steps, producing ManNAc-6-phosphate, which is then converted to Neu5Ac-9-phosphate and finally to Neu5Ac. Cells can also take up exogenous ManNAc and phosphorylate it to ManNAc-6-P, contributing to intracellular Neu5Ac production.

ManNAc is also part of bacterial sialic acid pathways, where it is produced and metabolized by enzymes such as NanE and NanK. It is used in research as a substrate to study glycosylation and the metabolic flux toward sialic acids.

In biomedical research, ManNAc and analogs have been explored as potential therapies for disorders involving impaired sialic acid biosynthesis, including GNE-related myopathies, but no widely approved indications exist. In the laboratory, ManNAc is used as a reagent for glycobiology experiments and metabolic labeling.

See also: sialic acid, N-acetylneuraminic acid, glycosylation, GNE.