Multiple Substrates for Paraoxonase-1 during Oxidation of Phosphatidylcholine by Peroxynitrite

• Published in: Biochemical and biophysical research communications 2002-01, Vol.290 (1), p.391-396
• Main Authors: Ahmed, Zakaria, Ravandi, Amir, Maguire, Graham F., Emili, Andrew, Draganov, Dragomir, La Du, Bert N., Kuksis, Arnis, Connelly, Philip W.
• Format: Article
• Language: English
• Subjects: apolipoprotein A-I; Aryldialkylphosphatase; core aldehydes; electrospray; Enzyme Inhibitors - pharmacology; Esterases - blood; Esterases - chemistry; Esterases - metabolism; Humans; Hydrolysis; hydroperoxides; isoprostanes; Lipoproteins - metabolism; lysophosphatidylcholine; mass spectrometry; Models, Chemical; Molsidomine - analogs & derivatives; Molsidomine - pharmacology; Oxygen - metabolism; paraoxonase-1; Peroxynitrous Acid - metabolism; Phosphatidylcholines - metabolism; Phosphatidylcholines - pharmacology; Phosphatidylethanolamines - pharmacology; Protein Binding; Proteolipids - metabolism; Spectrometry, Mass, Electrospray Ionization; Substrate Specificity; Time Factors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.6150

Paraoxonase (PON-1) is a high-density lipoprotein (HDL)-bound enzyme with activity toward multiple substrates. It hydrolyzes organic phosphate and aromatic carboxylic acid esters. It also inhibits accumulation of oxidized phospholipids in plasma lipoproteins by a mechanism yet to be determined. Therefore, we subjected apolipoprotein A-I proteoliposomes containing either 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine or 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine to oxidation by a peroxynitrite generator, SIN-1, in the presence and absence of purified PON-1. PON-1 modified the proportion of oxidation products without affecting the overall extent of PC oxidation. However, in the presence of PON-1, phosphatidylcholine isoprostanes were hydrolyzed to lysophosphatidylcholine. In addition, PON-1 hydrolyzed the phosphatidylcholine core aldehydes 1-palmitoyl-2-(9-oxo)nonanoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-(5-oxo)valeroyl-sn-glycero-3-phosphocholine to lysophosphatidylcholine. This hydrolysis was not affected by pefabloc, a serine esterase inhibitor. There was no detectable release of linoleate, arachidonate, or their hydroperoxy or hydroxy derivatives in the presence of PON-1. We conclude that PON-1 minimizes the accumulation of phosphatidylcholine oxidation products by the hydrolysis of phosphatidylcholine isoprostanes and core aldehydes to lysophosphatidylcholine with a serine esterase-independent mechanism.