Biosynthesis of platelet-activating factor. I. Evidence for an acetyl-transferase activity in murine macrophages

Biochim Biophys Acta. 1982 Jan 15;710(1):23-31. doi: 10.1016/0005-2760(82)90185-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism*
  • Animals
  • Blood Coagulation Factors / biosynthesis*
  • Calcium / pharmacology
  • Cell Adhesion
  • Kinetics
  • Lysophosphatidylcholines / biosynthesis*
  • Macrophages / enzymology*
  • Magnesium / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Platelet Activating Factor
  • Platelet Aggregation
  • Rats
  • Rats, Inbred Strains

Substances

  • Blood Coagulation Factors
  • Lysophosphatidylcholines
  • Platelet Activating Factor
  • Acetyltransferases
  • Magnesium
  • Calcium