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 (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.
Jaeken
J
J
Department of Pediatrics, University of Leuven, Belgium.
Pirard
M
M
Adamowicz
M
M
Pronicka
E
E
van Schaftingen
E
E
D000818:Animals; D018981:Congenital Disorders of Glycosylation / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005633:Fructose Intolerance / Q000378:metabolism*; D005636:Fructosephosphates / Q000737:chemistry / Q000494:pharmacology*; D030342:Genetic Diseases, Inborn; D005966:Glucuronidase / Q000097:blood; D006031:Glycosylation; D006801:Humans; D008359:Mannose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D017875:Phosphotransferases (Phosphomutases) / Q000378:metabolism; D051381:Rats; D001619:beta-N-Acetylhexosaminidases / Q000097:blood
D004791:Enzyme Inhibitors; D005636:Fructosephosphates; C032284:fructose-1-phosphate; D005966:Glucuronidase; D001619:beta-N-Acetylhexosaminidases; D008359:Mannose-6-Phosphate Isomerase; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase