title: Ether phospholipids as inhibitors of the arachidonoyl-CoA: 1-acyl-sn-glycero-3-phosphocholine acyltransferase in macrophages.
abstract: 1-Alkylglycerophosphatide analogs which are known to activate macrophages to enhanced tumor cytotoxicity are structurally closely related to 1-acyl-sn-glycero-3-phosphocholine. In this study we have examined the influence of some of these compounds and of platelet-activating factor (PAF-acether, 1-0-alkyl-2-0-acetyl-sn-glycero-3-phosphocholine) on the arachidonoyl-CoA: 1-acyl-sn-glycero-3-phosphocholine acyltransferase (EC 2.3.1.23) in homogenate of bone-marrow-derived murine macrophages. This enzyme is suggested to be involved in the control of the availability of the icosanoid precursor, arachidonic acid. Kinetic experiments revealed apparent Km and V values for 1-palmitoyl-sn-glycero-3-phosphocholine of 6.0 microM and 16.10 nmol/mg protein per min, respectively. When the 1-palmitoyl-sn-glycero-3-phosphocholine concentration was equal to Km, the enzyme was dose-dependently inhibited by 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine with a 50% inhibition at 30 microM. The kinetic parameters in the presence of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (K'm = 10.0 microM, V' = 11.40 nmol X mg-1 X min-1) suggest that this alkyl phospholipid is a mixed-type inhibitor. All other alkyl analogs tested (1-O-methyl-2-O-octadecyl-rac-glycerol-3-phosphocholine, racemic PAF-acether, L-PAF-acether, D-1-O-hexadecyl-sn-glycero-3-phosphocholine, 1-O-octadecyl-rac-glycero-3-phosphocholine) inhibited the enzyme to various degrees. Arachidonic acid transfer to the 1-alkylglycerophosphatide analogs themselves could be ruled out under the assay conditions used. Therefore, we conclude that the arachidonoyl-CoA: 1-acyl-sn-glycero-3-phosphocholine acyltransferase can be inhibited by synthetic and naturally occurring ether phospholipids in homogenate of bone-marrow-derived murine macrophages.
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors*; D000214:Acyl Coenzyme A / Q000494:pharmacology; D000215:Acylation; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D010742:Phospholipid Ethers; D010743:Phospholipids / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*
chemical_list: D000214:Acyl Coenzyme A; D008244:Lysophosphatidylcholines; D010742:Phospholipid Ethers; D010743:Phospholipids; D010972:Platelet Activating Factor; C026563:arachidonyl-coenzyme A; C026659:edelfosine; D000217:Acyltransferases; D008243:1-Acylglycerophosphocholine O-Acyltransferase