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

Pediatr Res. 1996 Nov;40(5):764-6. doi: 10.1203/00006450-199611000-00017.


Isoelectrofocusing of serum sialotransferrins from patients with untreated hereditary fructose intolerance (HFI) 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 (Ki congruent to 40 microM) of phosphomannose isomerase (EC, the first enzyme of the N-glycosylation pathway thus explaining the N-glycosylation disturbances in HFI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Congenital Disorders of Glycosylation / blood
  • Enzyme Inhibitors / pharmacology*
  • Fructose Intolerance / metabolism*
  • Fructosephosphates / chemistry
  • Fructosephosphates / pharmacology*
  • Genetic Diseases, Inborn
  • Glucuronidase / blood
  • Glycosylation
  • Humans
  • Mannose-6-Phosphate Isomerase / antagonists & inhibitors*
  • Molecular Structure
  • Phosphotransferases (Phosphomutases) / metabolism
  • Rats
  • beta-N-Acetylhexosaminidases / blood


  • Enzyme Inhibitors
  • Fructosephosphates
  • fructose-1-phosphate
  • Glucuronidase
  • beta-N-Acetylhexosaminidases
  • Mannose-6-Phosphate Isomerase
  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase