ROLE OF LIPID STRUCTURE IN THE ACTIVATION OF PHOSPHOLIPASE-A(2) BY PEROXIDIZED PHOSPHOLIPIDS

The time course of hydrolysis of a mixed phospholipid substrate contai ning bovine liver 1,2-diacyl-sn-glycero-3-phosphocholine (PC) and 1,2- diacyl-sn-glycero-3-phospho-ethanolamine (PE) catalyzed by Crotalus ad amanteus phospholipase A2 was measured before and after peroxidation o f the lipid substrate. The rate of hydrolysis was increased after pero xidation by an iron/adenosine diphosphate (ADP) system; the presence o f iron/ADP in the assay had a minimal inhibitory effect. The rate of l ipid hydrolysis was also increased after the substrate was peroxidized by heat and O2. Similarly, peroxidation increased the rate of hydroly sis 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 i n the absence of PE, peroxidation dramatically increased the rate of l ipid hydrolysis. In addition, the rate of hydrolysis of the unoxidizab le lipid I-palmitoyl-2-[1-C-14]oleoyl PC incorporated into PC/PE lipos omes 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 largel y to a preference for peroxidized phospholipid molecules as substrates and that peroxidation of host lipid does not significantly increase t he rate of hydrolysis of nonoxidized lipids.