Human beta-glucuronidase. II. Fate of infused human placental beta-glucuronidase in the rat.

Human placental beta-glucuronidase could be identified in rat organs by heating organ extracts to 65 degrees which selectively inactivated endogenous rat enzyme. Infused enzyme was rapidly cleared from rat plasma (t0.5 of 3.5 min). From 50-60% of the infused dose was accounted for in rat liver and spleen 24 hr after infusion. Removal of abdominal viscera, including the spleen, and interruption of the portal circulation before infusion slowed the plasma disappearance (t0.5 of 60 min) and allowed significant uptake by bone and other organs. Subcellular fractionation of liver 18 hr postinfusion localized the human enzyme in the mitochondrial-lysosomal fraction. The half-disappearance times of infused human enzyme were 2.6 days in rat liver and 5.8 days in rat spleen. Periodate treatment of human placental beta-glucuronidase destroyed 90% of its binding to concanavalin A-Sephadex rose, reduced its heat stability, and abolished its rapid clearance from rat plasma after infusion.