Inhibition of human and rat lipoprotein lipase by high-density lipoprotein.
The hydrolysis in vitro of preactivated Intralipid (an artificial triacylglycerol-phospholipid emulsion) by rat adipose tissue lipoprotein lipase is inhibited by rat high-density lipoprotein (HDL). The aim of this work was to investigate whether human lipoprotein lipase was also inhibited, the mechanism of inhibition of the rat enzyme by HDL, and the role of the various individual apolipoproteins. Both human and rat lipoprotein lipase from post-heparin plasma are inhibited by HDL. This inhibition is considerably decreased if the HDL is first made 'apolipoprotein poor' by removal of some transferable apolipoproteins. In contrast, both native and apolipoprotein poor HDL inhibit the hydrolysis of Intralipid by rat hepatic lipase. Apolipoproteins C and E, either free in solution or attached to lipid vesicles, inhibit the hydrolysis of activated Intralipid by rat lipoprotein lipase to a maximum of 85% and 50%, respectively. Apolipoprotein A attached to vesicles gives little inhibition. HDL apolipoprotein and apolipoprotein C compete with the substrate for binding to lipoprotein lipase with apolipoprotein C having a higher affinity for the enzyme than HDL apolipoprotein. The inhibition of lipoprotein lipase by HDL can be explained by the association of the constituent apolipoproteins, in particular apolipoprotein C, with the enzyme so that there is less enzyme available to act on substrate.
D000818:Animals; D001056:Apolipoproteins C / Q000494:pharmacology; D001057:Apolipoproteins E / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008049:Lipase / Q000037:antagonists & inhibitors; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D051381:Rats
D001056:Apolipoproteins C; D001057:Apolipoproteins E; D005217:Fat Emulsions, Intravenous; D008075:Lipoproteins, HDL; D008049:Lipase; D008071:Lipoprotein Lipase