Abstract
Sialic acids (Sias) are acidic 9‑carbon monosaccharides. Both free Sias and conjugated Sias (sialylation) exist in the human body and have decisive impacts on human health and disease. Cellular free Sias are made via de novo biosynthesis, recycled from lysosomal salvage, and even by uptake of extracellular Sias, respectively. Sialylation of glycoproteins and glycolipids are catalyzed by sialyltransferases using CMP-Sia as the donor in the Golgi apparatus. In addition, free Sia can be degraded/catabolized into ManNAc and pyruvate in the cytosol. Overall, cellular free Sia and sialylation are kept at certain levels for normal cell functions. However, Sias deficiency and overproduction (accumulation), hyposialylation (undersialylation) and hypersialylation all cause disorders in the human body through a variety of mechanisms, but most of them are still not fully clarified. This review discusses recent understanding of disorders in Sia biosynthesis, salvage, catabolism, and sialylation pathways and therapeutic explorations for these disorders as well.