Effects of plasma apolipoproteins on lipoprotein lipase-mediated lipolysis of small and large lipid emulsions.
Large (ca. 120 nm) and small (ca. 35 nm) emulsions consisting of triolein (TO) and phosphatidylcholine (PC) were prepared as the primary protein-free models of chylomicrons and their remnants, respectively. Lipoprotein lipase (LPL)-mediated lipolysis of emulsion TO was retarded in chylomicron-free human plasma compared with the hydrolysis activated by isolated apolipoprotein C-II (apoC-II). In 30% plasma, free fatty acid (FFA) release rate was higher for large emulsions than for small ones, while both emulsions were hydrolyzed at similar rates in the presence of isolated apoC-II. Isolated apolipoprotein C-III (apoC-III) or apolipoprotein E (apoE) worked as LPL-inhibitor of the lipolysis activated by apoC-II. It was also observed that apolipoprotein A-I (apoA-I) showed distinct inhibitory effects on the lipolysis of large and small emulsions: more effective inhibition for small emulsions. Kinetic analyses showed that K(m)(app) and V(max)(app) for the lipolysis of emulsions were lower in the presence of 30% plasma than isolated apoC-II. ApoA-I also markedly decreased K(m)(app) and V(max)(app) for LPL-catalyzed hydrolysis of both emulsions. In chylomicron-free serum, the density of bound apoA-I at small emulsion surfaces was about three fold greater than large emulsion surfaces, but the binding densities of apoC-II, apoC-III and apoE were less for small emulsion surfaces than for large ones, suggesting that apoA-I preferentially binds to small particles and displaces other exchangeable apolipoproteins from particle surfaces. These results indicate that, in addition to the well known inhibitory effects of apoC-III and apoE, apoA-I in plasma regulates the lipolysis of triglyceride (TG)-rich emulsions and lipoproteins in a size-dependent manner.
Yamamoto
Mayumi
M
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Morita
Shin-ya
SY
Kumon
Michiko
M
Kawabe
Misa
M
Nishitsuji
Kazuchika
K
Saito
Hiroyuki
H
Vertut-Doï
Aline
A
Nakano
Minoru
M
Handa
Tetsurou
T
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism / Q000494:pharmacology; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D001056:Apolipoproteins C / Q000378:metabolism / Q000494:pharmacology; D001057:Apolipoproteins E / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D004655:Emulsions; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism*; D008892:Milk / Q000201:enzymology; D010713:Phosphatidylcholines / Q000378:metabolism; D011485:Protein Binding; D014304:Triolein / Q000378:metabolism
D016632:Apolipoprotein A-I; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D004655:Emulsions; D010713:Phosphatidylcholines; D014304:Triolein; D008071:Lipoprotein Lipase