Fate of lipoprotein lipase taken up by the rat liver. Evidence for a conformational change with loss of catalytic activity.
When isolated rat livers were perfused with medium containing lipoprotein lipase, 40-60% was taken up during a single passage. This value was similar for lipoprotein lipase derived from culture medium of rat preadipocytes, and for lipoprotein lipase purified from bovine milk. It was also, similar, irrespective of the lipoprotein lipase concentration, at least up to 1 microgram/ml. Immediately following its uptake by the liver, a large fraction of the lipoprotein lipase could be released by heparin, but the magnitude of this fraction decreased with time. The enzyme lost its catalytic activity rather rapidly, but its degradation to acid-soluble products, or to larger fragments, was much slower. On heparin-agarose chromatography, the enzyme taken up by the liver eluted at a lower salt concentration than the original lipoprotein lipase preparation. This change in affinity for heparin suggests that the originally dimeric lipoprotein lipase had dissociated into monomers, in analogy to the findings in model experiments. It is suggested that the initial uptake of lipoprotein lipase occurs by binding to a polyanion at the liver cell surface. This is followed by endocytosis and dissociation of the enzyme from its heparan sulfate-like binding site. Acidification of the endosome may cause a conformational change in the lipase molecule with dissociation to inactive monomers, preceding ultimate proteolytic degradation.
Chajek-Shaul
T
T
Department of Medicine B, Hadassah University Hospital, Jerusalem, Israel.
Friedman
G
G
Ziv
E
E
Bar-On
H
H
Bengtsson-Olivecrona
G
G
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D005260:Female; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008892:Milk / Q000201:enzymology; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains
D008071:Lipoprotein Lipase