title: N-acetylneuraminic acid and sialoglycoconjugate metabolism in fibroblasts from a patient with generalized N-acetylneuraminic acid storage disease.
abstract: Cultured skin fibroblasts from a patient suffering from generalized N-acetylneuraminic acid storage disease were found to accumulate large amounts (approx. 4.0 mumol/g fresh weight) of free N-acetylneuraminic acid in a lysosome-enriched subcellular fraction. However, there were no detectable deficiencies in lysosomal hydrolase activities (including neuraminidase), and the activities of CMP-N-acetylneuraminic acid synthetase and N-acetylneuraminic acid aldolase were within normal limits. The cellular glycoconjugate composition was normal, and pathologic fibroblasts labeled with either [3H]glucosamine-HCl or N-[3H]acetylmannosamine showed a marked accumulation of labeled free N-acetylneuraminic acid, along with elevated incorporation into sialoglycoconjugates. Neither normal nor pathologic fibroblasts secreted labeled free N-acetylneuraminic acid into the culture medium. These results are consistent with an inherited defect in N-acetylneuraminic acid reutilization, resulting in the lysosomal accumulation of the free monosaccharide in generalized N-acetylneuraminic acid storage disease.
mesh_terms: D002239:Carbohydrate Metabolism, Inborn Errors / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D019158:N-Acetylneuraminic Acid; D012016:Reference Values; D012794:Sialic Acids / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D014316:Tritium
chemical_list: D005732:Gangliosides; D006595:Hexosamines; D012794:Sialic Acids; D012795:Sialoglycoproteins; D014316:Tritium; D019158:N-Acetylneuraminic Acid; D005944:Glucosamine; C002022:N-acetylmannosamine