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

Abstract

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 5.3.1.8), the first enzyme of the N-glycosylation pathway thus explaining the N-glycosylation disturbances in HFI.

• Authors: J Jaeken, M Pirard, M Adamowicz, E Pronicka, E van Schaftingen
• Journal: Pediatric research (Pediatr Res) Vol. 40 Issue 5 Pg. 764-6 (Nov 1996) ISSN: 0031-3998 [Print] United States
• PMID: 8910943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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