Biosynthesis of platelet activating factor. Substrate specificity of 1-alkyl-2-lyso-sn-glycero-3-phosphocholine:acetyl-CoA acetyltransferase in rat spleen microsomes.
The substrate requirements and specificity of 1-alkyl-2-lyso-sn-glycero-3-phosphocholine (alkyllyso-GPC):acetyl-CoA acetyltransferase were investigated. The following findings were observed. 1) When the ether bond of alkyllyso-GPC is substituted with an ester linkage, the resulting compound, palmitoyllyso-GPC, can serve as a substrate, albeit at a reduced rate (50%). In addition, palmitoyllyso-GPC is a competitive inhibitor in the reaction with respect to concentration dependence of alkyllyso-GPC and a noncompetitive inhibitor when the concentrations of acetyl-CoA are varied. 2) Octadecyllyso-GPC is acetylated at a slightly higher rate than hexadecyllyso-GPC and unsaturated alkyllyso-GPC is a preferable substrate to its saturated counterpart. 3) The homologous series of short chain acyl-CoAs demonstrate an inverse relationship of chain length with the values of their apparent Km and Vmax, e.g. the longer the acyl-CoA chain, the smaller the values of Vmax and apparent Km. 4) The effect of polar head group modification of alkyllyso-GPC on the acetyltransferase activity is related to the degree of methylation of the amine group. The choline base analog gives the highest enzyme activity and the ethanolamine derivative is the least active, while N', N'-dimethylethanolamine and monomethylethanolamine analogs are the substrates with intermediate activities. These results on substrate selectivity of acetyltransferase correlate with the known structural requirements essential for the biological activities elicited by platelet activating factor and thus suggest that the acetyltransferase activating factor and thus suggest that the acetyltransferase may be important in governing the chemical structure of platelet activating factor synthesized in vivo.
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D013154:Spleen / Q000201:enzymology*; D013379:Substrate Specificity; D014316:Tritium
D010972:Platelet Activating Factor; D014316:Tritium; D000123:Acetyltransferases; C027628:acetyl-CoA-1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase