Free N-acetylneuraminic acid (NANA) storage disorders: evidence for defective NANA transport across the lysosomal membrane.
To study the biochemical defect underlying N-acetylneuraminic acid (NANA) storage disorders (NSD), a tritium-labeled NANA-methylester was prepared and its metabolism was studied in normal and mutant human fibroblasts. The uptake of methylester, its conversion into free NANA, and the release of free NANA was studied in lysosome-enriched fractions. In three clinically different types of NSD accumulation of free NANA was observed and the half-life of this compound was significantly increased. Our observations indicate the existence of a transport system for NANA across the lysosomal membrane, which is deficient in all variants of NSD.
D001692:Biological Transport; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019158:N-Acetylneuraminic Acid; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism*
D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid