A pressure‐dependent model for the regulation of lipoprotein lipase by apolipoprotein C‐II

Abstract

Apolipoprotein C-II (apoC-II) is the co-factor for lipoprotein lipase (LPL) at the surface of triacylglycerol-rich lipoproteins. LPL hydrolyzes triacylglycerol, which increases local surface pressure as amphipathic products accumulate at the lipoprotein surface. To understand how apoC-II adapts to these pressure changes, we characterized the behavior of apoC-II at lipid/water interfaces. ApoC-II adsorption to a triacylglycerol/water interface resulted in large increases in surface pressure. ApoC-II was exchangeable at this interface and desorbed on interfacial compressions. These compressions increase pressure and mimic the actions of LPL. Analysis of gradual compressions showed that apoC-II undergoes a two-step desorption. This indicates that lipid-bound apoC-II exhibits multiple conformations. We characterized apoC-II at phospholipid/triacylglycerol/water interfaces, which more closely mimic lipoprotein surfaces. ApoC-II molecules completely desorbed on interfacial compressions at retention pressures higher than those of the other apoCs. It is therefore unlikely that apoC-I and apoC-III inhibit LPL via displacement of apoC-II from lipoproteins. On rapid compressions and re-expansions, re-adsorption of apoC-II increased pressure by lower amounts than initial adsorption. This indicates that apoC-II removes phospholipid from the interface on desorption. These results suggest that apoC-II regulates the activity of LPL in a pressure-dependent manner. ApoC-II binds lipoproteins and is the co-factor for LPL as pressure increases. Above its retention pressure, apoC-II desorbs and removes phospholipid, which allows LPL to remain bound.