Identification of the metabolic defect in sialuria

J Biol Chem. 1989 Oct 25;264(30):17635-6.

Abstract

Sialuria is a rare inborn error of metabolism, the hallmarks of which are moderate developmental retardation, coarse facial features, and an enormous amount of free N-acetylneuraminic acid (sialic acid) in the urine. Until now, the basic biochemical defect in this disorder has remained uncertain. In this report, the activity of the rate-limiting enzyme in the biosynthesis of sialic acid has been measured directly in whole cell lysates by a highly sensitive assay. With this technique, the basic defect in sialuria has been identified unequivocally as the loss of feedback control of uridine diphosphate N-acetylglucosamine 2-epimerase by cytidine monophosphate N-acetylneuraminic acid with resultant overproduction of sialic acid.

MeSH terms

  • Carbohydrate Epimerases / metabolism
  • Carbohydrate Metabolism, Inborn Errors / metabolism*
  • Carrier Proteins*
  • Cells, Cultured
  • Feedback
  • Fibroblasts / metabolism
  • Hexosamines
  • Humans
  • Kinetics
  • N-Acetylneuraminic Acid
  • Reference Values
  • Sialic Acids / urine*
  • Skin / metabolism

Substances

  • Carrier Proteins
  • Hexosamines
  • Sialic Acids
  • Carbohydrate Epimerases
  • N-acyl-D-glucosamine 2-epimerase
  • RENBP protein, human
  • N-Acetylneuraminic Acid
  • N-acetylmannosamine