Biosynthesis of platelet-activating factor. I. Evidence for an acetyl-transferase activity in murine macrophages.
Platelet-activating factor (PAF-acether; 1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) is released from murine peritoneal adherent cells by inflammatory and non-inflammatory stimuli. We have found, in extracts from these cells, an enzyme activity that synthesizes. PAF-acether from synthetic lyso-PAF-acether by transferring the acetyl moiety of acetyl-coenzyme A onto the lyso-PAF-acether molecule. The enzyme is stabilized by 1 mM dithiothreitol, is calcium-dependent, has an apparent Km of 172 microM for acetyl-CoA and is active in a 6-8 pH range. When the acetyl-CoA substrate is replaced by propionyl-CoA, an ether lipid is produced which turns out to be as potent an aggregating agent as PAF-acether. In all cases, the products of the reaction were characterized by their behaviour in platelet-aggregation tests and their high-pressure liquid chromatography (HPLC) elution profiles. The precise definition of this acetyl-transferase is of primary importance for the development of new pharmacological agents capable of moduling a potent platelet aggregating factor.
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000096:biosynthesis*; D008264:Macrophages / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor; D010974:Platelet Aggregation; D051381:Rats; D011919:Rats, Inbred Strains
D001779:Blood Coagulation Factors; D008244:Lysophosphatidylcholines; D010972:Platelet Activating Factor; D000123:Acetyltransferases; D008274:Magnesium; D002118:Calcium