Multiple substrates for paraoxonase-1 during oxidation of phosphatidylcholine by peroxynitrite.
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.
Ahmed
Zakaria
Z
J. Alick Little Lipid Research Laboratory, St. Michael's Hospital, University of Toronto, 38 Shuter Street, Toronto, Ontario M5B 1A6, Canada.
Ravandi
Amir
A
Maguire
Graham F
GF
Emili
Andrew
A
Draganov
Dragomir
D
La Du
Bert N
BN
Kuksis
Arnis
A
Connelly
Philip W
PW
D043303:Aryldialkylphosphatase; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004950:Esterases / Q000097:blood / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008074:Lipoproteins / Q000378:metabolism; D008956:Models, Chemical; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011485:Protein Binding; D011510:Proteolipids / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013379:Substrate Specificity; D013997:Time Factors
C096875:1-palmitoyl-2-arachidonyl-glycero-3-phosphoethanolamine; D004791:Enzyme Inhibitors; D008074:Lipoproteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011510:Proteolipids; C020485:proteoliposomes; D030421:Peroxynitrous Acid; C002385:linsidomine; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; D008981:Molsidomine; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D010100:Oxygen