Role of lipid structure in the activation of phospholipase A2 by peroxidized phospholipids.
The time course of hydrolysis of a mixed phospholipid substrate containing bovine liver 1,2-diacyl-sn-glycero-3-phosphocholine (PC) and 1,2-diacyl-sn-glycero-3-phosphoethanolamine (PE) catalyzed by Crotalus adamanteus phospholipase A2 was measured before and after peroxidation of the lipid substrate. The rate of hydrolysis was increased after peroxidation by an iron/adenosine diphosphate (ADP) system; the presence of iron/ADP in the assay had a minimal inhibitory effect. The rate of lipid hydrolysis was also increased after the substrate was peroxidized by heat and O2. Similarly, peroxidation increased the rate of hydrolysis of soy PC liposomes that did not contain PE. In order to minimize interfacial factors that may result in an increase in rate, the lipids were solubilized in Triton X-100. In mixtures of Triton with soy PC in the absence of PE, peroxidation dramatically increased the rate of lipid hydrolysis. In addition, the rate of hydrolysis of the unoxidizable lipid 1-palmitoyl-2-[1-14C]oleoyl PC incorporated into PC/PE liposomes was unaffected by peroxidation of the host lipid. These data are consistent with the notions that the increase in rate of hydrolysis of peroxidized PC substrates catalyzed by phospholipase A2 is due largely to a preference for peroxidized phospholipid molecules as substrates and that peroxidation of host lipid does not significantly increase the rate of hydrolysis of nonoxidized lipids.
McLean
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LR
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Hagaman
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Davidson
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D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005296:Ferrous Compounds / Q000378:metabolism; D006358:Hot Temperature; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism* / Q000494:pharmacology; D008066:Lipolysis; D017830:Octoxynol; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism* / Q000494:pharmacology; D011092:Polyethylene Glycols; D012911:Snakes; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D005296:Ferrous Compounds; D008054:Lipid Peroxides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; C020748:ferrous sulfate; D011092:Polyethylene Glycols; D000244:Adenosine Diphosphate; D017830:Octoxynol; D010741:Phospholipases A; D054467:Phospholipases A2