title: 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 surface area decreases and amphipathic products transiently accumulate at the lipoprotein surface. To understand how apoC-II adapts to these pressure changes, we characterized the behavior of apoC-II at multiple 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 surface pressure and mimic the action of LPL. Analysis of gradual compressions showed that apoC-II undergoes a two-step desorption, which indicates that lipid-bound apoC-II can exhibit at least two conformations. We characterized apoC-II at phospholipid/triacylglycerol/water interfaces, which more closely mimic lipoprotein surfaces. ApoC-II had a large exclusion pressure, similar to that of apoC-I and apoC-III. However, apoC-II desorbed at retention pressures higher than those seen with the other apoCs. This suggests that it is unlikely that apoC-I and apoC-III inhibit LPL via displacement of apoC-II from the lipoprotein surface. Upon rapid compressions and re-expansions, re-adsorption of apoC-II increased pressure by lower amounts than its initial adsorption. This indicates that apoC-II removed phospholipid from the interface upon desorption. These results suggest that apoC-II regulates the activity of LPL in a pressure-dependent manner. ApoC-II is provided as a component of triacylglycerol-rich lipoproteins and is the co-factor for LPL as pressure increases. Above its retention pressure, apoC-II desorbs and removes phospholipid. This triggers release of LPL from lipoproteins.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Meyers
authors.affiliation: Department of Medical Biosciences/Physiological Chemistry, Umeå University, SE-901 87 Umeå, Sweden; Department of Medicine, UCLA, Los Angeles, California 90095.
authors.forename: Mikael
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Department of Medical Biosciences/Physiological Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118. Electronic address: dmsmall@bu.edu.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Small
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism; D011312:Pressure; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013499:Surface Properties; D014867:Water / Q000378:metabolism
chemical_list: D053304:Apolipoprotein C-II; D010743:Phospholipids; D014867:Water; D008071:Lipoprotein Lipase
keywords: apolipoprotein; lipase; lipid droplet; lipoprotein metabolism; low-density lipoprotein (LDL); triglyceride