Activation of lipoprotein lipase by apolipoprotein C-II is modulated by the COOH terminal region of apolipoprotein C-III.
The in vitro effect of apolipoprotein C-II (apo C-II) on the apolipoprotein C-III (apo C-III) induced activation of bovine milk lipoprotein lipase (LPL) was studied in vitro using a synthetic substrate. Apo C-III effectively inhibited, in a dose-dependent manner, the activation of lipoprotein lipase induced by apo C-II. A 3-fold molar apo C-III excess decreased the lipoprotein lipase activity by 25%. Thrombin cleavage of apo C-III produced two fragments: only fragment 41-79 retained the inhibitory activity and was equipotent to native apo C-III1 on a molar basis. Neither displacement of apo C-II from the substrate, as determined using 125I-labeled apo C-II, nor the charge carried by sialic residues of apo C-III, as demonstrated in experiments performed after neuraminidase treatment, accounted for this effect. I speculate that apo C-III may act by inhibiting the apo C-II-LPL interaction.
Catapano
A L
AL
Institute of Pharmacological Sciences, Milan, Italy.
D000818:Animals; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D004789:Enzyme Activation; D005260:Female; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008892:Milk / Q000201:enzymology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding
D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D010446:Peptide Fragments; D008071:Lipoprotein Lipase