The reactions of hypochlorous acid, the reactive oxygen species produced by myeloperoxidase, with lipids

Myeloperoxidase (MPO), an abundant enzyme in phagocytes, has been implicate d in the pathogenesis of various inflammatory diseases including atheroscle rosis. The major oxidant produced by MPO, hypochlorous acid (HOCl), is able to modify a great variety of biomolecules by chlorination and/or oxidation . In this paper the reactions of lipids (preferentially unsaturated fatty a cids and cholesterol) with either reagent HOCl or HOCl generated by the MPO -hydrogen peroxide-chloride system are reviewed. One of the major issues has been whether the reaction of HOCl with lipids o f low density lipoprotein (LDL) yields predominantly chlorohydrins or lipid hydroperoxides. Electrospray mass spectrometry provided direct evidence th at chlorohydrins rather than peroxides are the major products of HOCl- or M PO-treated LDL phosphatidylcholines. Nevertheless lipid peroxidation is a p ossible alternative reaction of HOCl with polyunsaturated fatty acids if an additional radical source such as pre-formed lipid hydroperoxides is avail able. In phospholipids carrying a primary amino group such as phosphatidyle thanolamine chloramines are the preferred products compared to chlorohydrin s. Cholesterol can be converted by HOCl to great variety of oxysterols besi des three isomers of chlorohydrins. For the situation in vivo it appears that the type of reaction occurring be tween HOCl and lipids would very much depend on the circumstances, e.g. the pH and the presence of radical initiators. The biological effects of lipid chlorohydrins are not yet well understood. It has been shown that chlorohydrins of both unsaturated fatty acids as wel l as of cholesterol may cause lysis of target cells, possibly by disruption of membrane structures.