Strategies for the analysis of chlorinated lipids in biological systems.
Myeloperoxidase-derived HOCl reacts with the vinyl ether bond of plasmalogens yielding α-chlorofatty aldehydes. These chlorinated aldehydes can be purified using thin-layer chromatography, which is essential for subsequent analysis of extracts from some tissues such as myocardium. The α-chlorofatty aldehyde 2-chlorohexadecanal (2-ClHDA) is quantified after conversion to its pentafluorobenzyl oxime derivative using gas chromatography-mass spectrometry and negative-ion chemical ionization detection. 2-ClHDA accumulates in activated human neutrophils and monocytes, as well as in atherosclerotic lesions and infarcted myocardium. Metabolites of 2-ClHDA have also been identified, including the oxidation product, 2-chlorohexadecanoic acid (2-ClHA), and the reduction product, 2-chlorohexadecanol. 2-ClHA can be quantified using LC-MS with selected reaction monitoring (SRM) detection. 2-ClHA can be ω-oxidized by hepatocytes and subsequently β-oxidized from the ω-end, leading to the production of the dicarboxylic acid, 2-chloroadipic acid. This dicarboxylic acid is excreted in the urine and can also be quantified using LC-MS methods with SRM detection. Quantitative analyses of these novel chlorinated lipids are essential to identify the role of these lipids in leukocyte-mediated injury and disease.
Department of Biochemistry and Molecular Biology, School of Medicine, and Center for Cardiovascular Research, Saint Louis University, St. Louis, MO 63104, USA.
Bradley K
BK
Wacker
Carolyn J
CJ
Albert
Benjamin A
BA
Ford
David A
DA
Ford
D000447:Aldehydes / Q000032:analysis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008055:Lipids / Q000032:analysis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D010169:Palmitic Acids / Q000032:analysis* / Q000737:chemistry
C432398:2-chlorohexadecanal; C532464:2-chlorohexadecanoic acid; D000447:Aldehydes; D008055:Lipids; D010169:Palmitic Acids