Phosphohexosyl recognition is a general characteristic of pinocytosis of lysosomal glycosidases by human fibroblasts.

A C T We recently presented data showing that mannose-6-phosphate was a potent competitive inhibitor of pinocytosis of human platelet f8-glucuronidase, and that treatment of "high-uptake" forms of the enzyme with alkaline phosphatase destroyed the high-uptake property of the enzyme without diminish- ing 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 phos- phohexosyl moiety. Results presented here show that mannose-6-phosphate is also a potent inhibitor of pinocytosis of the following enzyme preparations: (a) ,8-glucuronidase from human spleen, liver, placenta, and urine; (b) /3-hexosaminidase and f8-galactosidase from human platelets; (c) f-hexosaminidase from human fibroblast secretions. Alkaline phosphatase treatment of all of these enzymes except 8-galactosi- dase, which was unstable to the incubation condi- tions 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.