Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat.
Heparin and heparin partially depolymerized by enzymic digestion were separated into six size fractions. Hep 1 (tetrasaccharides), with a mean M(r) of 1200, did not release significant amounts of either lipoprotein lipase (LPL) or hepatic lipase (HL) on intravenous injection into rats. Hep 2 (mainly octa- and deca-saccharides), with a mean M(r) of 2400-3000, released both lipases. To evoke the same plasma activity of LPL and HL required about 10 times more by weight, or about 40 times more molecules, of this heparin than of hep 5 (mean M(r) 12,000, similar to conventional heparin). Hep 5 impeded binding and degradation of 125I-labelled bovine LPL by perfused rat livers. In contrast, hep 2 had no detectable effect on these processes. This demonstrates a difference between the sites in the liver that mediate binding, uptake and degradation of LPL, and the extrahepatic sites that bind functional LPL, and the hepatic sites that bind functional HL. After injection of 3.25 mg of hep 5/kg body weight, plasma LPL activity rapidly rose and then remained high for at least 1 h. With hep 2, plasma LPL also rose rapidly, but then decreased to almost basal by 1 h. When a labelled triacylglycerol emulsion was injected 1 h after the heparins, the fractional catabolic rate was enhanced in the rats that had received conventional heparin, as expected from the high plasma LPL activity, but decreased compared with controls in rats that had received hep 2, indicating that available LPL had been depleted through enhanced transport to and uptake in the liver.
Liu
G
G
Department of Medical Biochemistry and Biophysics, University of Umeå, Sweden.
Hultin
M
M
Ostergaard
P
P
Olivecrona
T
T
D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008049:Lipase / Q000097:blood / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D006493:Heparin; D008049:Lipase; D008071:Lipoprotein Lipase