Properties of PAF-synthesizing phosphocholinetransferase and evidence for lysoPAF acetyltransferase activity in rat brain.
Several reports have indicated that platelet-activating factor (PAF) may play a role in the physiopathology of nervous tissue. We previously have demonstrated the presence, in the microsomal fractions of rat brain, of a phosphocholinetransferase which is able to synthesize PAF by the de novo pathway. The presence of dithiothreitol in the medium increases the rate of PAF biosynthesis, whereas it inhibits the synthesis of long-chain alkylacyl- and diacyl-glycerophosphocholines (GPC), including dioctanoyl-GPC. This and other properties, such as pH dependence and thermal stability, indicate that rat brain may have two distinct enzymes for the synthesis of PAF and other choline phospholipids. The affinity of these enzymes for CDPcholine is similar to that reported for other tissues, the Km being 42 microns and 55 microns with alkylacetylglycerol and dioctanoylglycerol as lipid substrates, respectively. The Vmax values were 3.0 and 2.2 nmol/mg prot/min for PAF and dioctanoyl-GPC, respectively. In addition, it was shown that the microsomal fraction of rat brain contains an acetyltransferase which can convert lysoPAF to PAF. Since it has been reported previously that brain tissue possesses phospholipase A2 activity that can hydrolyze alkylacyl-GPC to lysoPAF, we conclude that brain tissue has all enzymic activities for the synthesis of PAF by the "remodeling pathway". The role of the two routes of PAF biosynthesis in nervous tissue remains to be established.
Goracci
G
G
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Perugia, Italy.
Francescangeli
E
E
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D010972:Platelet Activating Factor; D003566:Cytidine Diphosphate Choline; D000123:Acetyltransferases; C027628:acetyl-CoA-1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase; C046035:1-alkylglycerophosphocholine acetyltransferase