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. 2021 Mar 1;131(5):e137681. doi: 10.1172/JCI137681

Figure 1. Metabolic pathway associated with mannose and Sias.

Figure 1

Mannose is associated with Sia metabolism. Mannose is phosphorylated to Man-6P by hexokinase and ATP as a cofactor. Man-6P is converted to Kdn with NANS and N-acetylneuraminic acid phosphatase (NANP), and Kdn can be converted to CMP-Kdn with CMP N-acetylneuraminic acid synthetase (CMAS) in some species. Man-6P can also be transformed into Man-1P by phosphomannomutase 2 (PMM2). Man-6P is also converted to Fru-6P by PMI. Fru-6P is transformed into uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is then converted to ManNAc-6P via GNE. ManNAc-6P is converted to Neu5Ac via NANS and NANP. NPL regulates Neu5Ac concentrations by mediating the reversible conversion to ManNAc and pyruvate, but human NPL does not work on Kdn. Neu5Ac is converted to CMP-Neu5Ac with CMAS, and CMP-Neu5Ac is converted to CMP-N-glycolylneuraminic acid (Neu5Gc) by CMAH. Humans cannot synthesize Neu5Gc because of inactivation of the CMAH gene about 2–3 million years ago.