Neu5Gc

Neu5Gc, short for N-glycolylneuraminic acid, is a sialic acid variant commonly found on glycoproteins and glycolipids of many mammals. In most mammals the cytidine monophosphate (CMP)-sialic acid hydroxylase CMAH converts Neu5Ac to Neu5Gc, leading to widespread tissue expression. Humans, however, carry an inactivated CMAH gene, and cannot synthesize Neu5Gc. Consequently, Neu5Gc is not produced endogenously by human cells, though small amounts can be incorporated from dietary sources into human glycoproteins and glycolipids via metabolic pathways.

Because Neu5Gc is foreign to the human immune system, most people harbor circulating anti-Neu5Gc antibodies of various isotypes. When dietary Neu5Gc is incorporated into human tissues, these antibodies can bind to Neu5Gc-containing glycoconjugates and form immune complexes, a phenomenon referred to as xenosialitis. This chronic, low-grade inflammation has been proposed as a contributing factor in several disease processes, including cancer, atherosclerosis, and autoimmune or inflammatory conditions, though the extent of its impact remains under investigation.

Research uses CMAH-knockout mice and human tissues to study Neu5Gc uptake, distribution, and immune reactivity. Analytical methods include mass spectrometry and antibody-based assays to detect Neu5Gc and anti-Neu5Gc antibodies. Dietary guidance is not definitive, but red meat and certain dairy products are recognized sources of dietary Neu5Gc.

Overall, Neu5Gc represents a non-human sialic acid with potential immunological and disease relevance in humans due to dietary incorporation and preformed antibodies.