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.
Vilaró
S
S
Department of Physiological Chemistry, University of Umeå, Sweden.
Llobera
M
M
Bengtsson-Olivecrona
G
G
Olivecrona
T
T
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002463:Cell Membrane Permeability; D003078:Colchicine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006493:Heparin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D006493:Heparin; D008071:Lipoprotein Lipase; D003078:Colchicine