Fig. 7
From: Targeted metabolomic evaluation of peripheral blood mononucleated cells from patients with PMM2-CDG
Schematic representation of the metabolic pathways directly affected by PMM2 malfunctioning in PMM2-CDG patients. Increase in mannose-6-phosphate (Man-6-P) causes increased concentrations of fructose-6-phosphate (Fru-6-P) first, and subsequent increased concentrations of glucose-6-phosphate (Glu-6-P), because of the equilibrium reactions catalyzed by mannose phosphate isomerase (MPI) and glucose phosphate isomerase (GPI), respectively. Higher Glu-6-P availability leads to increased formation of UDP-glucose (UDP-Glc). At the same time, the increase of Fru-6-P availability also allows to maintain an adequate synthesis of UDP-GlcNac, thus ensuring a significant level, although partial, of protein glycosylation. Higher levels of UDP-Glc could be responsible for increased rate of glycogen synthesis, thus explaining the abnormal glycogen accumulation observed in the liver of PMM2-CDG patients. Arrows in red indicate the reactions occurring under these pathological conditions. Compounds in the faint yellow boxes are those undergoing significant increases.
