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 () encodes the 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 , could help to understand their function and reduce the amount of Neu5Gc.
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http://dx.doi.org/10.3390/biology11060903 | DOI Listing |
J Control Release
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State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address:
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March 2025
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, United States.
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Division of Molecular Epidemiology, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573, Japan; Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address:
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Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; UCIBIO-Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; CDG & Allies-Professionals and Patient Associations International Network (CDG & Allies-PPAIN), Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal. Electronic address:
Defects in sialic acid metabolism disrupt the sialylation of glycoproteins and glycolipids, contributing to a spectrum of diseases, including GNE myopathy (GNEM). This rare disorder is caused by mutations in the GNE gene that encodes for a bifunctional enzyme required for sialic acid biosynthesis, resulting in progressive muscle atrophy and weakness. There is no approved treatment for GNEM, and the number of affected individuals is underestimated.
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