♦ See referenced article, J. Biol. Chem. 2014, 289, 6751–6761
Mannose is an essential sugar in N-linked oligosaccharides. The sugar is made by phosphomannose isomerase from glucose. Deficiencies in the enzyme lead to a congenital glycosylation disorder. Mannose can also enter the body through supplements, which has been a treatment approach for the glycosylation disorder. In this Paper of the Week, Hudson H. Freeze at the Sanford-Burnham Medical Research Institute in California and colleagues describe a method based on gas chromatography and mass spectrometry to quantitatively measure the amount of mannose derived in cells from the phosphomannose isomerase and other potential pathways. They established that normal human fibroblasts got 25–30% of their mannose from exogenous mannose; fibroblasts lacking phosphomannose isomerase got 80% of their mannose directly from exogenous supplements. This finding suggests that the enzyme activity and the concentration of external mannose both influence metabolic flux of the N-glycosylation pathway. The authors say, “This quantitative assessment of mannose contribution and its metabolic fate provides information that can help bolster therapeutic strategies for treating glycosylation disorders with exogenous mannose.”
Mannose and glucose metabolic pathway.