ABSTRACT
Peroxidases are important enzymes that are present in leukocytes and some tissues that have important physiological roles in the innate immune system and have been implicated in a broad spectrum of tissue pathologies. Three peroxidases that
Introduction: Peroxidase Products Targeting the Phospholipid Milieu of Membranes and the Liberation of Halogenated Lipids .......................................77 MPO-and EPO-Containing Leukocytes in Innate Immunity, Inammation, and Disease ..............................................................................................................80 Plasmalogen-Derived Halogenated Lipids ............................................................... 83
Plasmalogens: An Abundant Phospholipid Subclass Found in Mammalian Tissues ............................................................................. 83 Liberation of α-Halofatty Aldehydes from Plasmalogens: Chemical Identity ................................................................................................................84 Liberation of α-Halofatty Aldehydes from Plasmalogens: Biological Production in Leukocytes and under In Vivo Inammatory Conditions .............85
α-Halofatty Aldehyde Metabolism: Potential Mechanisms for the Action of Halogenated Lipids ..............................................................................................87 Biological Targets of α-Chlorofatty Aldehyde and Its Metabolites ......................... 89 Other Halolipids Produced from Hypohalous Acids Targeting Lipids Other Than Plasmalogens .................................................................................................. 91 Conclusions and Future Directions ..........................................................................92 References ................................................................................................................93
produce reactive halogenating species have been shown to target conventional lipids producing halogenated lipids. These peroxidases include myeloperoxidase (MPO), eosinophil peroxidase (EPO), and thyroid peroxidase (TPO). These peroxidases are important in both physiological and pathophysiological repair mechanisms, innate immunity and thyroid hormone production. The reactive halogenating species produced by these peroxidases include HOCl, Cl2, HOBr, Br2, BrCl, and either I+ or I0. Figure 4.1 shows the structural motifs of plasmenylethanolamine that are targeted by reactive halogenating species, which include the vinyl ether bond of plasmalogens, double bonds of alkenes, and primary amines of polar lipids. Although the in vivo oxidation of conventional lipids by reactive halogenating systems is considered to be off-site targeting of host tissue, identifying the halogenated lipids that are produced as well as understanding the role of the loss of their precursors may provide important insights into physiological and pathophysiological functions mediated by this system.
