Effect of Heparin on the Kinetics of Guinea Pig and Human Postheparin Lipase Activity

Summary Lipoprotein lipase plays a major role in mammalian lipid metabolism. It is the key enzyme for hydrolysis of triglycerides contained in very-low-density lipoproteins (VLDL) and chylomicrons. Triglyceride hydrolysis by this enzyme requires that peptides be present on the chylomicron and VLDL surfaces. When artificial triglyceride emulsions are used in a postheparin lipase system, triglyceride hydrolysis depends upon emulsion activation by these same peptides. When triglyceride concentration is held constant in the assay system, an increase in high density lipoproteins or VLDL produces a Michaelis-Menten hyperbolic increase in lipase activity. Previous work has suggested that heparin added to the assay system modifies the kinetics of interaction of postheparin lipase with its triglyceride substrate. The result is a sigmoid substrate saturation curve, with heparin apparently acting as an allosteric modifier of the lipase. This study supports the role of heparin as an allosteric modifier of postheparin lipase. The postheparin lipase substrate saturation curves shift to the right as heparin concentration increases in the assay system. Moreover, the results indicate an allosteric effect of heparin on human postheparin lipase. Because of the importance of triglyceride hydrolysis in lipoprotein metabolism, abnormalities in its regulatory control could be important in the relationship of lipoproteins to atherosclerosis. The author gratefully acknowledges the technical assistance of Mrs. Jeanne Morelli.