Lipoprotein lipase uptake by the liver: localization, turnover, and metabolic role.

We have studied the binding and metabolism of 125I-labeled bovine lipoprotein lipase (LPL) by use of isolated, perfused rat livers. Our data suggest the presence of two types of binding sites, i.e., heparin-sensitive sites that bind primarily the catalytically active form of the lipase and are present at the endothelium in all blood vessels and heparin-insensitive sites that bind both active and inactive forms and are present only within the sinusoids. Forty minutes after uptake by the liver, approximately 50% of the LPL had lost its catalytic activity or been degraded. Three processes were evident: 1) colchicine-sensitive degradation to acid-soluble products, 2) partial proteolysis to fragments similar to those formed by limited digestion with trypsin or plasmin, and 3) a conformational change leading to loss of catalytic activity. Exogenous LPL bound in the liver caused a dramatic increase in the utilization of a perfused triacylglycerol emulsion (Intralipid), with rapid formation of free fatty acids and water-soluble metabolites. When the liver was flushed with heparin, it lost its ability to utilize the fat emulsion. Measurement of the hepatic extraction showed that rat livers take up 100-200 mU endogenous LPL per hour.