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 untre ated hereditary fructose intolerance (HF-I) shows a cathodal shift sim ilar to that in carbohydrate-deficient glycoprotein (CDG) syndrome typ e I and in untreated galactosemia. This report is on serum lysosomal e nzyme abnormalities in untreated HFI that are identical to those found in CDG syndrome type I but different. from those in untreated galacto semia, 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 o f the N-glycosylation pathway thus explaining the N-glycosylation dist urbances in HFI.