Abstract
Plasmalogens contain a vinyl ether bond linking the sn-1 aliphatic chain to the glycerol backbone of this predominant phospholipid molecular subclass, which is found in many mammalian tissues. The present study demonstrates that the vinyl ether bond of plasmalogens is a molecular target of the reactive chlorinating species produced by myeloperoxidase. Analysis by thin layer chromatography revealed that reactive chlorinating species produced by myeloperoxidase target the vinyl ether bond of the plasmalogen, lysoplasmenylcholine (1-O-hexadec-1'-enyl-sn-glycero-3-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 (i.e. the vinyl ether) because the dimethyl acetal of hexadecanal produced by acid methanolysis derivatization was no longer present. Electrospray ionization mass spectrometry of the myeloperoxidase-generated neutral lipid product was consistent with the production of a 16-carbon fatty aldehyde containing one chlorine atom. Furthermore, proton NMR analysis indicated that this neutral lipid product was a 2-chloro-fatty aldehyde. Additional structural analysis of this neutral lipid by gas chromatography-mass spectrometry of the underivatized product as well as its pentafluorobenzyl oxime-derivative product was consistent with the neutral lipid being 2-chlorohexadecanal. The reactive chlorinating species, hypochlorous acid and chlorine gas, both attacked the vinyl ether bond of lysoplasmenylcholine resulting in the production of 2-chlorohexadecanal. The production of 2-chlorohexadecanal was dependent on the presence of the plasmalogen masked aldehyde (i.e. the vinyl ether) in the substrate because the free fatty aldehyde, hexadecanal, was not converted to 2-chlorohexadecanal by the reactive chlorinating species generated by myeloperoxidase. 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 production of novel chlorinated fatty aldehydes.
Highlights
Plasmalogens contain a vinyl ether bond linking the sn-1 aliphatic chain to the glycerol backbone of this predominant phospholipid molecular subclass, which is found in many mammalian tissues
Analysis by thin layer chromatography revealed that reactive chlorinating species produced by myeloperoxidase target the vinyl ether bond of the plasmalogen, lysoplasmenylcholine (1-Ohexadec-1-enyl-sn-glycero-3-phosphorylcholine), resulting in the production of a neutral lipid
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 production of novel chlorinated fatty aldehydes
Summary
Plasmalogens, which are localized in the plasma membranes of mammalian cells [17], likely would be highly accessible molecular targets of the membrane-permeable, reactive chlorinating species generated by activated phagocytes. The present study tested the hypothesis that the vinyl ether of the sn-1 aliphatic chain of plasmalogens would be susceptible to chlorination by reactive chlorinating species produced by myeloperoxidase. The results demonstrate for the first time that reactive chlorinating species produced by myeloperoxidase are reactive with the masked aldehyde, vinyl ether linkage of plasmalogens resulting in the production of lysophospholipids and ␣-chloro-fatty aldehydes (see Scheme I). The production of ␣-chloro-fatty aldehydes by reactive chlorinating species generated by myeloperoxidase is specific for the masked aldehyde found in plasmalogens and is not produced from free fatty aldehydes or carboxy ester-linked aliphatic groups found at the sn-2 carbon of the plasmalogen glycerol backbone
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
