Role of Specific Glycopeptides of Human Serum Lipoproteins in the Activation of Lipoprotein Lipase

Abstract

Lipoprotein lipase forms an enzyme-substrate complex with fat emulsions in the presence of serum lipoproteins. Lipoproteins of very low density and high density have this property, but the former are much more active per unit weight of protein. In this investigation, the activity, expressed as quantity giving half-maximal rate of production of free fatty acids, of specific glycopeptides isolated from very low density and high density lipoproteins was tested in an incubation mixture containing lipoprotein lipase from cows' milk and 1.8 mg triglyceride per ml. The two major polypeptides of high density lipoproteins were virtually inactive in amounts up to 100 µg per ml. Activity of the unfractionated apoproteins of very low density lipoprotein was similar to that of the native lipoprotein (about 4 µg/ml). Two of its polypeptides were active: one with carboxyl-terminal glutamic acid at 0.45 to 0.60µg/ml and one with carboxyl-terminal alanine at 1.8.2.8 µg/ml. Some preparations of the latter peptide were less active and inhibited at high levels. Three other glycopeptides from very low density lipoprotein were inactive. Low density lipoprotein from subjects with primary biliary cirrhosis and a lipoprotein of density 1.04 to 1.06 from a subject with specific elevation of this fraction, both containing the active glycopeptides, had considerable activity (5 to 11 µg/ml). These studies indicate that specific glycopeptides are required for the action of lipoprotein lipase on emulsified triglycerides and suggest that they are important components of the mechanism for extra-hepatic utilization of plasma triglycerides.