N-Glycolylneuraminic acid, often shortened to Neu5Gc, is a sugar molecule belonging to a family called sialic acids, which are commonly found on the surfaces of cells. These molecules play a role in various biological processes, including how cells recognize and communicate with each other. This type of sialic acid also participates in immune responses and inflammation.
Understanding N-Glycolylneuraminic Acid
Neu5Gc is a specific form of sialic acid. It is widely present on cell surfaces in most mammals, where it attaches to the ends of sugar chains on glycoproteins and glycolipids. However, humans are unique among mammals because they do not naturally produce Neu5Gc.
This human-specific absence stems from a genetic mutation that occurred millions of years ago, estimated to be around 2.7 to 2.8 million years ago, just before the emergence of the genus Homo. This mutation affects the CMAH gene, which encodes the enzyme cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH). In other mammals, CMAH converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc, but the human CMAH gene has an inactivating deletion, preventing this conversion.
Dietary Sources and Human Absorption
Despite not producing Neu5Gc internally, humans acquire this sugar molecule primarily through their diet. Red meat, such as beef, lamb, and pork, along with some dairy products, are significant sources of Neu5Gc.
Once ingested, Neu5Gc can be absorbed into the human body. It is thought to enter cells through a process called macropinocytosis, where the cell engulfs external fluid and its contents. After entering the cell, Neu5Gc can be incorporated into human cells and tissues, becoming part of glycoproteins and glycolipids on cell surfaces.
The Human Immune Response
Because humans do not produce Neu5Gc, the human immune system identifies it as a foreign molecule when it is absorbed from food and incorporated into tissues. This recognition triggers the generation of specific antibodies, known as anti-Neu5Gc antibodies, against the molecule.
This phenomenon is referred to as “xeno-autoimmunity,” where the immune system reacts against a foreign molecule that has become integrated into the body’s own tissues. The chronic interaction between the incorporated Neu5Gc and these circulating anti-Neu5Gc antibodies can lead to ongoing inflammation, a condition sometimes called xenosialitis.
N-Glycolylneuraminic Acid and Health
The chronic immune response to dietary Neu5Gc and the resulting inflammation have potential implications for human health. Research suggests a role in promoting chronic inflammation, which is implicated in various conditions. Studies have linked anti-Neu5Gc antibodies and inflammation to certain types of cancer, particularly colorectal cancer, and other inflammatory diseases.
For example, long-term exposure to dietary Neu5Gc and circulating anti-Neu5Gc antibodies has been associated with an increased incidence of carcinomas in human-like Neu5Gc-deficient mice. This ongoing area of research explores how the interaction between ingested Neu5Gc and the human immune system might contribute to the development and progression of diseases like atherosclerosis and type 2 diabetes, which are also exacerbated by inflammation.