Overproduction of N-acetylneuraminic acid (Sialic acid) by sialuria fibroblasts

George H. Thomas, Linda W. Reynolds, Carol S. Miller

Research output: Contribution to journalArticle

Abstract

Fibroblasts from the original sialuria patient are shown to contain high levels of free sialic acid, i.e., an average of 87 versus a normal average of 2 nmol/mg of protein. Gas liquid chromatography-mass spectrometry analysis confirmed that the accumulated material is N-acetylneuraminic acid. Addition of D(+) glucosamine (0-5 mM) to the media of these cells increased the intracellular free sialic acid concentrations from 74 to 137 nmol/mg protein. In contrast, normal cells treated in an identical manner maintained their normal free sialic acid level of less than 4 nmol/mg protein. Addition of 20 mM N-acetylmannosamine in place of glucosamine resulted in a marked increase in free sialic acid in both the patient and the control, i.e., increases of 157 (from 95 to 252) and 120 (from 3 to 123) nmol/mg protein, respectively. Finally, while normal cells in the presence of glucosamine accu­mulated high levels of uridine diphosphate N-acetylhexo-samine, the patient's cells accumulated much lower amounts of this compound. It is concluded that the elevated sialic acid level in sialuria is due, at least in part, to overproduction of free N-acetylneuraminic acid. Indirect evidence is presented that this may result from either hyperactivity or increased levels of the enzyme (uridine diphosphate N-acetylglucosamine 2-epimerase) that has been shown in other tissues to convert uridine diphosphate N-acetylglucosamine to N-acetylmannosamine.

Original languageEnglish (US)
Pages (from-to)451-455
Number of pages5
JournalPediatric Research
Volume19
Issue number5
StatePublished - 1985

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Sialic Acid Storage Disease
N-Acetylneuraminic Acid
Fibroblasts
Glucosamine
Uridine Diphosphate N-Acetylglucosamine
Proteins
Racemases and Epimerases
Uridine Diphosphate
Gas Chromatography-Mass Spectrometry

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Thomas, G. H., Reynolds, L. W., & Miller, C. S. (1985). Overproduction of N-acetylneuraminic acid (Sialic acid) by sialuria fibroblasts. Pediatric Research, 19(5), 451-455.

Overproduction of N-acetylneuraminic acid (Sialic acid) by sialuria fibroblasts. / Thomas, George H.; Reynolds, Linda W.; Miller, Carol S.

In: Pediatric Research, Vol. 19, No. 5, 1985, p. 451-455.

Research output: Contribution to journalArticle

Thomas, GH, Reynolds, LW & Miller, CS 1985, 'Overproduction of N-acetylneuraminic acid (Sialic acid) by sialuria fibroblasts', Pediatric Research, vol. 19, no. 5, pp. 451-455.
Thomas, George H. ; Reynolds, Linda W. ; Miller, Carol S. / Overproduction of N-acetylneuraminic acid (Sialic acid) by sialuria fibroblasts. In: Pediatric Research. 1985 ; Vol. 19, No. 5. pp. 451-455.
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