Phosphohexosyl recognition is a general characteristic of pinocytosis of lysosomal glycosidases by human fibroblasts.
We recently presented data showing that mannose-6-phosphate was a potent competitive inhibitor of pinocytosis of human platelet beta-glucuronidase, and that treatment of "high-uptake" forms of the enzyme with alkaline phosphatase destroyed the high-uptake property of the enzyme without diminishing its catalytic activity. These data indicate that phosphate is a necessary component of the recognition marker on the enzyme for pinocytosis by human fibroblasts, and suggest that the phosphate on high-uptake forms of the enzyme is present as a phosphohexosyl moiety. Results presented here show that mannose-6-phosphate is also a potent inhibitor of pinocytosis of the following enzyme preparations: (a) beta-glucuronidase from human spleen, liver, placenta, and urine; (b) beta-hexosaminidase and beta-galactosidase from human platelets; (c) beta-hexosaminidase from human fibroblast secretions. Alkaline phosphatase treatment of all these enzymes except beta-galactosidase, which was unstable to the incubation conditions and could not be tested, greatly diminished the uptake activity of the enzymes without diminishing their catalytic activity. These results suggest that phosphohexosyl recognition is a general characteristic of pinocytosis of lysosomal glycosidases.
D000469:Alkaline Phosphatase / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology / Q000502:physiology*; D005696:Galactosidases / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006596:Hexosaminidases / Q000378:metabolism; D006600:Hexosephosphates / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology*; D008360:Mannosephosphates / Q000494:pharmacology; D010873:Pinocytosis
D006600:Hexosephosphates; D008360:Mannosephosphates; D000469:Alkaline Phosphatase; D005696:Galactosidases; D006026:Glycoside Hydrolases; D006596:Hexosaminidases; D005966:Glucuronidase