Studies of the pathogenesis of Gaucher's disease: tissue distribution and biliary excretion of [14C]L-glucosylceramide in rats.

The time course of the clearance from the blood and the tissue localization of [14C]L-glucosylceramide, a nonmetabolizable enantiomorph of D-glucosylceramide that accumulates in Gaucher's disease, has been determined. 14C-labeled L-glucosylceramide injected intravenously in the form of micelles or liposomes is rapidly removed from the circulation. Most of this lipid is taken up by the liver where it is found in both hepatocytes and nonparenchymal cells. This sphingolipid analog is promptly cleared from hepatocytes and a significant portion is recovered in the bile. The clearance of [14C]L-glucosylceramide from Kupffer cells is greatly prolonged in comparison with its brief residence in hepatocytes. These findings have significant implications regarding the pathogenesis and treatment of Gaucher's disease.