NDLI: Rabbit Serum Paraoxonase 3 (PON3) Is a High Density Lipoprotein-associated Lactonase and Protects Low Density Lipoprotein against Oxidation

Content Provider	Journal of Biological Chemistry (JBC)
Author	Draganov, Dragomir I. Stetson, Philip L. Watson, Catherine E. Billecke, Scott S. Du, Bert N. La
Abstract	The paraoxonase gene family contains at least three members: PON1, PON2, andPON3. The physiological roles of the corresponding gene products are still uncertain. Until recently, only the serum paraoxonase/arylesterase (PON1) had been purified and characterized. Here we report the purification, cloning, and characterization of rabbit serum PON3. PON3 is a 40-kDa protein associated with the high density lipoprotein fraction of serum. In contrast to PON1, PON3 has very limited arylesterase and no paraoxonase activities but rapidly hydrolyzes lactones such as statin prodrugs (e.g.lovastatin). These differences facilitated the complete separation of PON3 from PON1 during purification. PON3 hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents. We cloned PON3 from total rabbit liver RNA and expressed it in mammalian 293T/17 cells. The recombinant PON3 has the same apparent molecular mass and substrate specificity as the enzyme purified from serum. Rabbit serum PON3 is more efficient than rabbit PON1 in protecting low density lipoprotein from copper-induced oxidation. This is the first report that identifies a second PON enzyme in mammalian serum and the first to describe an enzymatic activity for PON3.
Related Links	http://www.jbc.org/content/275/43/33435.abstract
Ending Page	33442
Starting Page	33435
Page Count	8
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	43
Volume Number	275
DOI	10.1074/jbc.M004543200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2000-10-27
Access Restriction	Open
Subject Keyword	High density lipoprotein (HDL) Low density lipoprotein (LDL) Rabbit liver microsomal paraoxonase (MsPON) Polyacrylamide gel electrophoresis (PAGE) High performance liquid chromatography (HPLC) Very low density lipoproteins (VLDL) High performance gel filtration chromatography (HPGC) Apolipoprotein (apo) Platelet-activated factor acetyl hydrolase (PAF-AH) Reverse transcriptase-polymerase chain reaction (RT-PCR) LIPIDS AND LIPOPROTEINS
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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