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Clinical Chemistry 0: clinchem.2004.034439v1, 2004; 10.1373/clinchem.2004.034439
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Received on March 18, 2004
Accepted on August 31, 2004

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Distribution Spectrum of Paraoxonase Activity in HDL Fractions

Christoph Bergmeier 1*, Rüdiger Siekmeier 2, Werner Groß 1

1 Labor für Angewandte Biochemie, Gustav-Embden-Zentrum für Biologische Chemie, Klinikum der J.W. Goethe-Universität, Frankfurt/Main, Germany
2 Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Bonn, Germany

* To whom correspondence should be addressed. E-mail: cbergmei{at}stud.uni-frankfurt.de.

Background: Paraoxonase (PON1) associated with HDL can be regarded as a cardio- and vasoprotective enzyme. However, because HDL is not a homogeneous fraction, it is important to investigate in which subgroups of HDL active PON1 is located. It would also be useful to determine density profiles of the HDL proteins apolipoprotein E (ApoE) and ApoJ.

Methods: We investigated the density range of HDL ({rho} = 1.063-1.256 kg/L) in healthy individuals, using the ultracentrifugation reference method and a newly introduced automated fractionation method. Profiles of PON1 activity and ApoA-I, ApoA-II, ApoE, ApoJ, and cholesterol concentrations were obtained by use of various density gradients.

Results: PON1 activity was highest in the more dense HDL3 and VHDL fractions where PON1 was not dissociated from the particles during centrifugation. The fraction in density range 1.175-1.185 kg/L showed not only the highest PON1 activity, but also the highest specific activity (activity per HDL particle). This fraction was the least-dense fraction containing both ApoE and ApoJ. Only the Q192R polymorphism had an effect on the distribution profile of PON1 activity. In contrast, L55M and the T(-107)C polymorphisms (determined by a novel nonradioactive method) were without effect on the density distribution of PON1 activity.

Conclusion: The HDL3 fraction, which is important in reverse cholesterol transport, also carries the highest PON1 activity.


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