Reactive chlorinating species produced by myeloperoxidase target the vinyl ether bond of plasmalogens: identification of 2-chlorohexadecanal.
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.
Albert
C J
CJ
Department of Biochemistry and Molecular Biology, St. Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
Crowley
J R
JR
Hsu
F F
FF
Thukkani
A K
AK
Ford
D A
DA
D000447:Aldehydes / Q000032:analysis*; D000818:Animals; D002713:Chlorine / Q000737:chemistry* / Q000378:metabolism; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D006863:Hydrogen-Ion Concentration; D006997:Hypochlorous Acid / Q000737:chemistry* / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000096:biosynthesis; D008246:Lysophospholipids / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010955:Plasmalogens / Q000378:metabolism*; D014753:Vinyl Compounds / Q000378:metabolism
C432398:2-chlorohexadecanal; D000447:Aldehydes; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010955:Plasmalogens; D014753:Vinyl Compounds; C032459:choline plasmalogens; C021215:lysoplasmalogens; C100195:vinyl ether; D002713:Chlorine; D006997:Hypochlorous Acid; D009195:Peroxidase