Exclusive association of paraoxonase 1 with high-density lipoprotein particles in apolipoprotein A-I deficiency

Paraoxonasel (PON1) is a high-density lipoprotein (HDL)-associated protein which removes peroxidized lipids from lipoproteins. It has been proposed th at apolipoprotein A-I (apoA-I) is an important determinant for its stabiliz ation on HDL. However, little is known about its existence and activity in an apoA-I-deficient state in humans. To characterize the nature of PON1 in apoA-I deficiency, we investigated PON1 in an apoA-I-deficient patient. Whe n serum was analyzed on fast protein liquid chromatography, PON1 protein wa s distributed almost exclusively on HDL despite the absence of apoA-I; on t he other hand, 38.5% of PON1 protein was found in the lipoprotein-free frac tion when the lipoproteins were fractionated through ultracentrifugation. T he stability of PON1 activity in the patient serum was almost the same as i n the normal control sera throughout incubation at 14 degreesC for 7 days. However, when the sera were incubated at 37 degreesC for 24 h, its activity declined more than those in the normal controls (19% versus 4% reduction o f the initial values). Our results demonstrated that PON1 protein possesses a preferential association with HDL even in the absence of apoA-I, althoug h apoA-I is a crucial factor for the maximal activity and stabilization of PON1. (C) 2001 Elsevier Science.