Apolipoprotein C-II deficiency. The role of apolipoprotein C-II in the hydrolysis of triacylglycerol-rich lipoproteins.

Kinetic studies were performed incubating lipoprotein lipase and hepatic triacylglycerol lipase from human postheparin plasma with triacylglycerol-rich lipoproteins from two patients with apolipoprotein C-II deficiency. These lipoproteins differed in their lipid and apolipoprotein composition from normal very-low-density lipoproteins and chylomicrons. The addition of isolated apolipoprotein C-II and normal or apolipoprotein C-II-deficient high-density lipoproteins caused an increase of Vmax and a decrease of the Km for lipoprotein lipase-induced hydrolysis. Hepatic triacylglycerol lipase activity was not influenced by the presence of apolipoprotein C-II in the incubation medium, but was inhibited by increasing amounts of high-density lipoproteins. Binding studies were performed in order to analyze the interactions between lipolytic enzymes, apolipoprotein C-II, and triacylglycerol-rich lipoproteins. Apolipoprotein C-II was, as expected, rapidly taken up by apolipoprotein C-II-deficient very-low-density lipoproteins and chylomicrons when they were incubated with normal high-density lipoproteins or with the purified apolipoprotein. This uptake was inhibited by the addition of increasing amounts of lipoprotein lipase in conditions in which no lipolysis could occur. Binding of lipoprotein lipase to apolipoprotein C-II-deficient very-low-density lipoproteins or chylomicrons was not affected by the addition of apolipoprotein C-II when an excess of triacylglycerol-rich lipoprotein was present. The stability of lipoprotein lipase was also studied. Apolipoprotein C-II and high-density lipoproteins were unable to prolong the half-life of the enzyme activity, while triacylglycerol-rich particles effectively stabilized lipoprotein lipase. We conclude that binding of lipoprotein lipase to the substrate surface is not affected by apolipoprotein C-II. It is more likely that the peptide catalyzes the conversion of lipoprotein lipase from a less to a more active form.