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 (Ki, 3.8 μM), showed competitive inhibition. Next, various lipids were examined for prevention against the inactivation of PON1 by ascorbate/Cu2+, which caused a remarkable (≥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 μM). 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 μM) 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.
Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization
- Views Icon Views
- Share Icon Share
S. Duy NGUYEN, Dai-Eun SOK; Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization. Biochem J 15 October 2003; 375 (2): 275–285. doi: https://doi.org/10.1042/bj20030663
Download citation file: