The regulation of CoA-independent transacylation reactions in neuronal nuclei by lysophospholipid, free fatty acid, and lysophospholipase: the control of nuclear lyso platelet-activating factor metabolism.

摘要: CoA-independent transacylase activities generating alkylacylglycerophosphocholine (AAGPC) from alkylglycerophosphocholine (1-alkyl GPC) were considerably enriched in neuronal nuclei isolated rabbit cerebral cortex. Specific nuclear transacylation 13 times the corresponding microsomal values. Several lysophospholipids, notably 1-acyl glycerophosphocholine (1-acyl GPC), 1-alkenyl GPC and GPE (1-alkenyl glycerophosphoethanolamine) inhibited of 1-alkyl GPC. The inhibitory effects seen presence MAFP (methyl arachidonoylfluorophosphonate) or free oleate, compounds that inhibit lysophospholipase. When preincubated with GPC, radioactive AAGPC product served as donor reactions, to generate In these 1-palmitoyl appeared be poor acceptor substrates, when compared analogues. oleate reactions containing boosted release AAGPC. These observations are particular relevance brain ischemia which lysophospholipid, fatty acid, platelet-activating factor (PAF) levels rise dramatically. PAF can made by acetylation is formed mechanisms. Yet also removes thus this enzyme activity regulate availability. Our indicate lysophospholipids promote formation via transacylation, while acid likely prolongs lifetime substrates lysophospholipase inhibition. Similarly, once formed, other effectively compete analogue reduce its conversion back transacylation. Free case, sustains lysophospholipid inhibitors Thus cycle may favour during ischemia, increasing for formation. generation considerable importance play regulatory roles transcription events associated inflammation.