Reactive chlorinating species produced by myeloperoxidase target the vinylether bond of plasmalogens - Identification of 8-chlorohexadecanal

Plasmalogens contain a vinyl ether bond linking the sn-l aliphatic chain to the glycerol backbone of this predominant phospholipid molecular subclass, which is found in many mammalian tissues. The present study demonstrates t hat the vinyl ether bond of plasmalogens is a molecular target of the react ive chlorinating species produced by myeloperoxidase, Analysis by thin laye r chromatography revealed that reactive chlorinating species produced by my eloperoxidase target the vinyl ether bond of the plasmalogen, lysoplasmenyl choline (1-O-hexadec-1 ''-enyl-sn-glycero3-phosphorylcholine), resulting in the production of a neutral lipid. Capillary gas chromatographic analyses demonstrated that the neutral lipid generated from lysoplasmenylcholine was neither hexadecanal nor did it contain masked hexadecanal (Le. the vinyl e ther) because the dimethyl acetal of hexadecanal produced by acid methanoly sis derivatization was no longer present. Electrospray ionization mass spec trometry of the myeloperoxidase-generated neutral Lipid product was consist ent with the production of a 16-carbon fatty aldehyde containing one chlori ne atom. Furthermore, proton NMR analysis indicated that this neutral lipid product was a 8-chloro-fatty aldehyde. Additional structural analysis of t his neutral lipid by gas chromatography-mass spectrometry of the underivati zed product as well as its pentafluorobenzyl oxime-derivative product was c onsistent with the neutral lipid being 2-chlorohexadecanal. The reactive ch lorinating species, hypochlorous acid and chlorine gas, both attacked the v inyl ether bond of lysoplasmenylcholine resulting in the production of 2-ch lorohexadecanal, The production of 2-chlorohexadecanal was dependent on the presence of the plasmalogen masked aldehyde (ae. the vinyl ether) in the s ubstrate because the free fatty aldehyde, hexadecanal, was not converted to 2-chlorohexadecanal by the reactive chlorinating species generated by myel operoxidase. Taken together, the present studies demonstrate for the first time the targeting of the vinyl ether bond of plasmalogens by the reactive chlorinating species produced by myeloperoxidase resulting in the productio n of novel chlorinated fatty aldehydes.