title: Characterization of phosphatidylcholine oxidation products by MALDI MS(n).
abstract: Phospholipid oxidation has been implicated in the pathogenesis and progression of numerous age-related and neurodegenerative diseases. Despite these implications, this broad class of biomolecules remains poorly characterized. In this work, the fragmentation patterns of [M + H](+) and [M + Na](+) ions of intact phosphatidylcholine oxidation products (OxPCs) were characterized by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI MS(n), n = 2, 3, and 4). MS(2) of both the [M + H](+) and [M + Na](+) ions of short-chain OxPCs yielded product ions related to the PC headgroup and the fatty acid substituents. MS(3) of the [M + Na - N(CH3)3](+) ions yielded fragmentation indicative of the OxPC modification; specifically, a product ion corresponding to the neutral loss of CO2 (NL of 44) was observed for OxPCs containing a terminal carboxylic acid rather than an aldehyde. Furthermore, MS(4) of the [M + Na - HPO4(CH2)2N(CH3)3](+) ions resulted in fragmentation pathways dependent on the sn-2 fatty acid chain length and type of functional group(s). Specifically, CHO-containing OxPCs with palmitic acid esterified to the sn-1 position of the glycerol backbone yielded a NL of 254, 2 u less than the nominal mass of palmitic acid, whereas the analogous terminal COOH-containing OxPCs demonstrated a NL of 256. Finally, the presence of a γ-ketone relative to the terminal carboxyl group resulted in C-C bond cleavages along the sn-2 substituent, providing diagnostic product ions for keto-containing OxPCs. This work illustrates the enhanced selectivity afforded by MS(n) on the linear ion trap and develops a method for the identification of individual products of PC oxidation.
authors.affiliation: Department of Chemistry, University of Florida , Gainesville, Florida 32611-7200, United States.
authors.forename: Whitney L
authors.initials: WL
authors.lastname: Stutts
authors.forename: Robert F
authors.initials: RF
authors.lastname: Menger
authors.forename: András
authors.initials: A
authors.lastname: Kiss
authors.forename: Ron M A
authors.initials: RM
authors.lastname: Heeren
authors.forename: Richard A
authors.initials: RA
authors.lastname: Yost
mesh_terms: D000818:Animals; D005260:Female; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000032:analysis* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D010713:Phosphatidylcholines