Quantitative aspects of pinocytosis and the intracellular fate of N-acetyl-alpha-D-glucosaminidase in Sanfilippo B fibroblasts.
The cellular uptake of N-acetyl-alpha-D-glucosaminidase, the deficient enzyme in Sanfilippo B disease, and the intracellular fate and metabolic effect of this enzyme have been investigated in Sanfilippo B and normal fibroblasts. For both genotypes the uptake is highly efficient (up to 0.025 mU/h/mg cell protein), specific and constant over a period of at least 6 days. It is probable that the enzyme protein is taken up by adsorptive pinocytosis. The enzymatic activity as well as the biological activity towards (35)SO(4)-labeled mucopolysaccharides persist in Sanfilippo B cells with a half-life of 34 h, indicating the intralysosomal localization of the pinocytosed enzyme. The data obtained are discussed with regard to a possible enzyme replacement therapy. For Sanfilippo B disease the doses used in the past are considered to be insufficient to cause measurable effects.
D000418:Albumins / Q000378:metabolism; D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D005838:Genotype; D006025:Glycosaminoglycans; D006207:Half-Life; D006596:Hexosaminidases / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology*; D007457:Iodine Radioisotopes; D010873:Pinocytosis; D012867:Skin / Q000166:cytology; D013460:Sulfur Isotopes
D000418:Albumins; D006025:Glycosaminoglycans; D007457:Iodine Radioisotopes; D013460:Sulfur Isotopes; D006596:Hexosaminidases