Effects of heparin on lipoprotein lipase from bovine milk.

The effect of heparin on the activity of lipoprotein lipase from bovine milk was investigated under conditions varying with regard to ionic strength, purity of enzyme, and mode of substrate activation. A crude enzyme (dialyzed skim milk) was studied, along with a purified preparation obtained by affinity chromatography on a column of heparin-substituted agarose. Serum, high density lipoproteins (HDLs), or very low density lipoproteins (VLDL) were used as activators. The activity of the enzyme varied with the ionic strength of the incubation medium. Maximal activity occurred at physiological salt concentration (I 0.16) ; at higher ionic strength the activity of the enzyme was depressed. This depression, due to inhibition along with inactivation of the enzyme, was impeded in the presence of heparin. The purified enzyme preparation was activated to about the same extent by either HDLa, VLDL, or serum. The effect of heparin on the lipolytic activities thus attained was relatively small. In contrast, the activity of the crude enzyme was extensively inhibited in the presence of serum but not in the presence of HDLB or VLDL. The inhibitory effect of serum was completely abolished by the addition of small amounts of heparin. The data obtained indicate that heparin may increase the activity of lipoprotein lipase, but only under otherwise suboptimal conditions. It is concluded that heparin stabilizes rather than stimulates the enzyme; furthermore, the effect of inhibitors is partly or completely abolished. Both enzyme preparations were shown to contain small amounts of endogenous heparin-like material. The functional significance of these components is discussed.