Document Detail

Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization.
MedLine Citation:
PMID:  12871208     Owner:  NLM     Status:  MEDLINE    
The effect of lipids on PON1 (paraoxonase 1), one of antioxidant proteins in high-density lipoprotein, was investigated in respect to inhibition, protection against oxidative inactivation, and stabilization. When the effect of lipids on the PON1 activity was examined, a remarkable inhibition was expressed by polyenoic fatty acids (C18:2-C20:5). Linoleic acid, the most potent ( K(i), 3.8 microM), showed competitive inhibition. Next, various lipids were examined for prevention against the inactivation of PON1 by ascorbate/Cu2+, which caused a remarkable (>or =90%) inactivation of PON1. Compared with saturated fatty acids (C6-C18), exhibiting a modest protection (9-40%), monoenoic acids (C16:1-C20:1) showed a greater maximal protective effect (Emax, 70-82%), with oleic acid being the most effective (EC50, 2.7 microM). In contrast, polyenoic acids showed no protection. Noteworthy, linoleic acid prohibited the protective action of oleic acid non-competitively. In the structure-activity relationship, a negatively charged group seems to be required for the protective action. Consistent with this, dioleoylphosphatidylglycerol, negatively charged, was more protective than dioleoylphosphatidylcholine. These data, together with requirement of Ca2+ (EC50, 0.6 microM) for the protective action, may support the existence of a specific site responsible for the protective action. A similar protective action of lipids was also observed in the inactivation of PON1 by ascorbate/Fe2+, peroxides or p -hydroxymercuribenzoate. Separately, PON1 was stabilized by oleic acid or oleoylated phospholipids, in combination with Ca2+, but not linoleic acid. These results suggest that in contrast to an adverse action of linoleic acid, monoenoic acids or their phospholipid derivatives play a beneficial role in protecting PON1 from oxidative inactivation as well as in stabilizing PON1.
Su Duy Nguyen; Dai-Eun Sok
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  375     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-06     Completed Date:  2004-02-18     Revised Date:  2010-09-14    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  275-85     Citation Subset:  IM    
College of Pharmacy, Chungnam National University, Gung-Dong, Yuseong-Ku, Taejon 305-764, South Korea.
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MeSH Terms
Aryldialkylphosphatase / metabolism*
Ascorbic Acid / pharmacology
Copper / pharmacology
Dose-Response Relationship, Drug
Enzyme Activation / drug effects
Enzyme Stability / drug effects
Fatty Acids / pharmacology
Hydroxymercuribenzoates / pharmacology
Oleic Acid / pharmacology*
Oxidants / pharmacology
Phospholipids / pharmacology*
Protease Inhibitors / pharmacology
Reg. No./Substance:
0/Fatty Acids; 0/Hydroxymercuribenzoates; 0/Oxidants; 0/Phospholipids; 0/Protease Inhibitors; 112-80-1/Oleic Acid; 138-85-2/4-hydroxymercuribenzoate; 50-81-7/Ascorbic Acid; 7440-50-8/Copper; EC

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