Hydrolysis of guinea pig nascent very low density lipoproteins catalyzed by lipoprotein lipase: activation by hjman apolipoprotein C-II.
Very low density lipoproteins isolated from guinea pig liver perfusate (VLDLp) lack the equivalent of human apolipoprotein C-II (apoC-II), the activator of lipoprotein lipase (LpL). These lipoproteins are therefore ideal substrates with which to investigate the mechanism by which apoC-II activates the enzyme. VLDLp binds apoC-II, and apoC-II associated with VLDLp markedly increases the rate of lipoprotein lipase-catalyzed hydrolysis of VLDLp-triglycerides. The activator potency of apoC-II is independent of the method of enrichment of VLDLp with apoC-II: delipidated human apoC-II and apoC-II transferred from human high density lipoproteins activate lipoprotein lipase to equal extents. ApoC-II causes pH-dependent changes in both apparent Km and VmaX of LpL-catalyzed hydrolysis of VLDLp-triglycerides. At pH l7.4--7.5, the major effects of apoC-II is to decrease the apparent Km by 3.3--4.0 fold. The apparent Vmax is increased 1.3-fold. At pH 6.5 and 8.5, the decrease of apparent Km is less marked, 1.6-fold and 1.4-fold, respectively. At pH 6.5, apoC-II increases the apparent Vmax ty 1.3-fold, while at pH 8.5 the primary effect of apoC-II is a 1.6-fold increase of apparent Vmax. Based on a simple kinetic model, the data suggest that apoC-II favors direct interaction between enzyme and triglyceride within the lipoprotein particle, as well as subsequent catalytic turnover.
D000818:Animals; D053304:Apolipoprotein C-II; D001053:Apolipoproteins / Q000494:pharmacology*; D001056:Apolipoproteins C; D004789:Enzyme Activation; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008854:Microscopy, Electron; D010477:Perfusion
D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001056:Apolipoproteins C; D008079:Lipoproteins, VLDL; D008071:Lipoprotein Lipase