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De novo biosynthesis of alkylacetylglycerols, a precursor of platelet activating factor (PAF)

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5283144
Alkylacetylglycerols are synthesized from 1-alkyl-2-lyso-sn-Gro-3-P via an acetyltransferase (I) and a phosphohydrolase (II). The final step that forms PAF in this pathway is catalyzed by a dithiothreitol-insensitive cholinephosphotransferase. This report describes properties of the acetyltransferase (I) and the phosphohydrolase (II). Results indicate the two activities are distinctly different from acetyl-CoA:1-alkyl-2-lyso-GroPCho acetyltransferase (III) and phosphatidic acid phosphohydrolase (IV), respectively. For example, 12.5 or 25 ..mu..M alkyl-lysoGroPCho did not affect the quantity of alkylacetylGroP and alkylacetylGro produced. The pH optimum for (I) was 8.4 as opposed to 6.9 for (III); also (I) and (III) had different sensitivities when microsomes were preincubated at various temperatures. Phosphatidic acid had no effect on the hydrolysis of the phosphate from alkylacetylGroP (II) and the pH optimum of the phosphohydrolase (II) was 6.6. Based on the distribution of marker enzymes, both acetyltransferases (I and III) and the alkylacetylGroP phosphohydrolase (II) are of microsomal origin. The phosphohydrolase (II) activity can be maximally inhibited by adding Na/sub 3/VO/sub 4/ and NaF to the assays and further decreased by incubating samples at a reduced temperature (23/sup 0/C); under these conditions the amounts of alkylacethlGroP is maximum. The newly identified enzyme activities (I and II) are relatively high in a variety of rat tissues, which suggests this de novo route is responsible for maintaining physiological levels of PAF.
Research Organization:
Oak Ridge Associated Universities, TN
DOE Contract Number:
AC05-76OR00033
OSTI ID:
5283144
Report Number(s):
CONF-8606151-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
Country of Publication:
United States
Language:
English