Submitted on April 15, 2004
Revised on August 18, 2004
Accepted on September 9, 2004
Preferential inhibition of paraoxonase activity of human paraoxonase1 by negatively-charged lipids
Su Duy Nguyen and Dai-Eun Sok
College of Pharmacy, Chungnam National University, Taejon, Taejon 305-764
Corresponding Author: daesok{at}cnu.ac.kr
To see the causes responsible for a preferential decrease of paraoxonase activity, which has been observed in serum of patients with cardiovascular diseases, the inactivation or inhibition of paraoxonase1 (PON1) by various endogenous factors was examined using paraoxon or phenyl acetate as substrate. When purified PON1 was incubated with various endogenous oxidants or aldehydes, they failed to cause a preferential reduction of paraoxonase activity, suggesting no participation of the inactivation mechanism in the preferential loss of paraoxonase activity. Next, when we examined the inhibition of PON1 activity by endogenous lipids, monoenoic acids such as palmitoleic acid or oleic acid inhibited paraoxonase activity preferentially, in contrast to a parallel inhibition of both activities by polyunsaturated or saturated acids. Noteworthy, oleoylglycine inhibited paraoxonase activity, but not arylesterase activity, complying with the selective inhibition of paraoxonase activity. Moreover, such a selective inhibition of paraoxonase activity was also expressed by lysophosphatidylglycerol or lysophosphatidylinositol, but neither lysophosphatidylserine nor lysophosphatidylcholine, indicating the importance of the type of head group. Further, such a preferential or selective inhibition of paraoxonase activity was also observed with PON1 associated with HDL or plasma. These data suggest that some negatively-charged lipids may correspond to factors causing the preferential inhibition of paraoxonase activity of PON1.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
