Inhibition of phosphomannose isomerase by fructose 1-phosphate: An explanation for defective N-glycosylation: In hereditary fructose intolerance

Isoelectrofocusing of serum sialotransferrins from patients with untreated hereditary fructose intolerance (HF-I) shows a cathodal shift similar to that in carbohydrate-deficient glycoprotein (CDG) syndrome type I and in untreated galactosemia. This report is on serum lysosomal enzyme abnormalities in untreated HFI that are identical to those found in CDG syndrome type I but different. from those in untreated galactosemia, CDG syndrome type I is due to phosphomannomutase deficiency, a defect in the early glycosylation pathway. It was found that fructose 1-phosphate is a potent competitive inhibitor (K-i similar or equal to 40 mu M) Of phosphomannose isomerase (EC 5.3.1.8), the first enzyme of the N-glycosylation pathway thus explaining the N-glycosylation disturbances in HFI.