Inhibition of lipoprotein lipase activity by synthetic peptides of apolipoprotein C-III.
In this study we have examined effects of synthetic polypeptide fragments of apoC-III on the kinetic properties of lipoprotein lipase (LPL) activity. Based on the loss of 79% of LPL-inhibitory activity after CNBr cleavage at the N-terminal portion of apoC-III and a systematic search for synthetic peptides with LPL-inhibitory activity spanning the apoC-III sequence, we concluded that the N-terminal domain is the most important in the modulation of LPL activity. In addition, there are multiple attachment sites in apoC-III for its interaction with LPL and these sites reside in the hydrophilic sequences of apoC-III. Probably for this reason the intact apo-CIII exhibited higher inhibitory potential than its peptide components. Based on the deduced inhibition constants derived for the synthetic apoC-III1-79 we concluded that apoC-III is likely to exhibit a physiological role in regulating LPL activity since the derived dissociation constants for the LPL-apoC-III interaction are within the physiological concentration range of plasma apoC-III. In addition, as the synthetic apoC-III1-79 lacks the carbohydrate moiety, we also concluded that the presence of the oligosaccharide in native apoC-III is not essential for its inhibitory activity on LPL. The fact that the I50 (concentration for inhibition of LPL at 50% activity) decreases for apoC-III-1 when assayed in the presence of apoC-II indicated that the activator actually caused an increased affinity between LPL and apoC-III and demonstrated that apoC-III does not compete for the activator site of apoC-II.
McConathy
W J
WJ
Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Gesquiere
J C
JC
Bass
H
H
Tartar
A
A
Fruchart
J C
JC
Wang
C S
CS
D000595:Amino Acid Sequence; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003488:Cyanogen Bromide; D006801:Humans; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008969:Molecular Sequence Data
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D008079:Lipoproteins, VLDL; D008071:Lipoprotein Lipase; D003488:Cyanogen Bromide