An Overview of the Importance and Value of Porcine Species in Sialic Acid Research

SIMPLE SUMMARY: Humans frequently interact with pigs and porcine meat is the most consumed red meat in the world. In addition, due to the many physiological and anatomical similarities shared between pigs and humans, in contrast to most mammalian species, pigs are a suitable model organism and pig organs can be used for xenotransplantation. However, one major challenge of porcine meat consumption and xenotransplantation is the xenoreactivity between red meat Neu5Gc sialic acid and human anti-Neu5Gc antibodies, which are associated with certain diseases and disorders. Furthermore, pigs express both α2-3 and α2-6 Sia linkages that could serve as viable receptors for viral infections, reassortments, and cross-species transmission of viruses. Therefore, pigs play a significant role in sialic acid research and, in general, in human health. ABSTRACT: Humans frequently interact with pigs, whose meat is also one of the primary sources of animal protein. They are one of the main species at the center of sialic acid (Sia) research. Sias are sugars at terminals of glycoconjugates, are expressed at the cell surfaces of mammals, and are important in cellular interactions. N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) are notable Sias in mammals. Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) encodes the CMAH enzyme that biosynthesizes Neu5Gc. Although humans cannot endogenously synthesize Neu5Gc due to the inactivation of this gene by a mutation, Neu5Gc can be metabolically incorporated into human tissues from red meat consumption. Interactions between Neu5Gc and human anti-Neu5Gc antibodies have been associated with certain diseases and disorders. In this review, we summarized the sialic acid metabolic pathway, its regulation and link to viral infections, as well as the importance of the pig as a model organism in Sia research, making it a possible source of Neu5Gc antigens affecting human health. Future research in solving the structures of crucial enzymes involved in Sia metabolism, as well as their regulation and interactions with other enzymes, especially CMAH, could help to understand their function and reduce the amount of Neu5Gc.