Metabolism of platelet activating factor in lung.
PAF is known to be produced by two independent enzymatic pathways. The remodeling route involves structural modification of a membrane phospholipid (1-alkyl-2-acyl-sn-glycero-3-phosphocholine) by substitution of an acetate for the acyl group at the sn-2 position. In contrast, the de novo pathway includes a sequence of acetylation, dephosphorylation, and phosphocholine addition, starting with the alkyl analog of lyso-phosphatidic acid. Hypersensitivity reactions with PAF as the autacoid are triggered by activation of the remodeling enzymes to produce excessive amounts of PAF. Inactivation of PAF occurs primarily by hydrolysis of the acetate group in a reaction catalyzed by acetylhydrolase. Results of our studies indicate that biosynthesis and catabolism of PAF by membrane preparations from both lung tissue and alveolar macrophages are qualitatively similar to that found in other cells. All of the enzymatic activities for both the remodeling and de novo pathways of PAF biosynthesis occur in the lung. Recent experiments indicate the initial reaction that produces lyso-PAF in the remodeling pathway of PAF biosynthesis is under the control of a CoA-independent transacylase that is capable of catalyzing both the hydrolysis of the acyl moiety of the alkylacylglycerophosphocholine precursor and its transfer to another lyso-phospholipid. The substrate specificity for the phospholipase A2 component of this reaction is for alkylacylglycerophosphocholines possessing arachidonate at the sn-2 position. Other polyunsaturated alkylacylglycerophosphocholines appear to be utilized as PAF precursors too, albeit to a lesser extent than the 20:4 species. The CoA-independent transacylase and its high affinity for the transfer of arachidonate to lyso-PAF appears to be a very prominent enzyme activity in rat lung membranes.
Snyder
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Medical Sciences Division, Oak Ridge Associated Universities, Tennessee 37831-0117.
Blank
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Lee
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D000818:Animals; D002460:Cell Line; D006801:Humans; D008168:Lung / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D051381:Rats
D010972:Platelet Activating Factor