The vinyl ether linkages of plasmalogens are favored targets for myeloperoxidase-derived oxidants: A kinetic study

Plasmalogens, which contain a vinyl ether bond, are major phospholipids of the plasma membranes of endothelial and vascular smooth muscle cells and cardiac myocytes. These lipids, in contrast to other phospholipids, have been reported to be targets of HOCl/HOBr generated by myeloperoxidase, with elevated levels of the products of these reactions (alpha-chloro/alpha-bromo aldehydes and unsaturated lysophospholipids) having been detected in human atherosclerotic lesions. The reason(s) for the targeting of this lipid class, over other phospholipids, is poorly understood, and is examined here. It is shown that HOCI and HOBr react with a model vinyl ether (ethylene glycol vinyl ether) 200-300-fold faster (k = 1.6 x 10(3) and 3.5 x 10(6) M(-1) s(-1), respectively) than with aliphatic alkenes (models of phospholipids). True plasmalogens react ca. 20-fold slower than the models. Chloramines and bromamines (from reaction of HOCl/HOBr with primary amines and alpha-amino groups) also react with vinyl ethers, unlike aliphatic alkenes, with k = 10(-3)-10(2) M(-1) s(-1) for chloramines (with the His side chain chloramine being the most reactive, k = 172 M(-1) s(-1)) and k = 10(3)-10(4) M(-1) s(-1) for bromamines. The bromamine rate constants are typically 10(5)-10(6) larger than those of the chloramines. Intermolecular vinyl ether oxidation by phospholipid headgroup bromamines can also occur. These kinetic data indicate that plasmalogens are significantly more susceptible to oxidation than the aliphatic alkenes of phospholipids, thereby rationalizing the detection of products from the former, but not the latter, in human atherosclerotic lesions.