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. 2021 Dec 17;12:799861. doi: 10.3389/fimmu.2021.799861

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Copyright © 2021 Hugonnet, Singh, Haas and von Gunten

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Sialic acid metabolism in humans. CMP-Neu5Ac mostly occurs in the cytoplasm except of the CMP-sialic acid synthase (CMAS)-mediated reaction which takes place in the nucleus. UDP-GlcNAc-2 epimerase (GNE) synthesizes N-acetylmannosamine (ManNAc) in two steps. Then, Neu5Ac synthase (NANS) generates ManNAc-9-P, which is then dephosphorylated by Neu5Ac-P-phosphatase (NANP) to generate free sialic acid in the cytoplasm. The free sialic acid can enter the nucleus to be linked to CMP (cytidine-5’-monophosphate). The CMP-Neu5Ac is transferred to the Golgi apparatus via SLC35A1 transporter (solute carrier family 35 member A1), where it is used as a substrate for sialylation by different sialyltransferases (SiaT). Sialylated glycoconjugates are then exported to the cellular membrane or secreted. They can also be broken down by various neuraminidases (NEU1-4) present in different cellular localizations. The released sialic acid can reenter the biosynthesis pathway. Illustration by Aldona von Gunten.