Formation of Aldehydic Phosphatidylcholines during the Anaerobic Decomposition of a Phosphatidylcholine Bearing the 9-Hydroperoxide of Linoleic Acid

Abstract

Lipid oxidation-derived carbonyl compounds are associated with the development of various physiological disorders. Formation of most of these products has recently been suggested to require further reactions of oxygen with lipid hydroperoxides. However, in rat and human tissues, the formation of 4-hydroxy-2-nonenal is greatly elevated during hypoxic/ischemic conditions. Furthermore, a previous study found an unexpected result that the decomposition of a phosphatidylcholine (PC) bearing the 13-hydroperoxide of linoleic acid under a nitrogen atmosphere afforded 9-oxononanoyl-PC rather than 13-oxo-9,11-tridecadienoyl-PC as the main aldehydic PC. In the present study, products of the anaerobic decomposition of a PC bearing the 9-hydroperoxide of linoleic acid were analysed by electrospray ionization mass spectrometry. 9-Oxononanoyl-PC (ONA-PC) and several well-known bioactive aldehydes including 12-oxo-9-hydroperoxy-(or oxo or hydroxy)-10-dodecenoyl-PCs were detected. Hydrolysis of the oxidized PC products, methylation of the acids obtained thereby, and subsequent gas chromatography-mass spectroscopy with electron impact ionization further confirmed structures of some of the key aldehydic PCs. Novel, hydroxyl radical-dependent mechanisms of formation of ONA-PC and peroxyl-radical dependent mechanisms of formation of the rest of the aldehydes are proposed. The latter mechanisms will mainly be relevant to tissue injury under hypoxic/anoxic conditions, while the former are relevant under both normoxia and hypoxia/anoxia.

Structural Analysis of Lipid Hydroperoxides Using Mass Spectrometry with Alkali Metals

“…As to which side is cleaved (i.e., methyl- or carbonyl-side C–C), α-cleavage preferred the reaction which generates stable fragment ions. For example, allyl radical ions and conjugated aldehyde ions are stable owing to the presence of a resonance or conjugated structure (Figure ) , and therefore abundantly produced ions such as m / z 207.1 for FA 18:2;10OOH and m / z 206.2 for FA 18:2;12OOH (Figures B and C). This also explains why the cleavage which generates unstable vinyl radical ions was not preferred.…”

Possible Glutathione Peroxidase 4-Independent Reduction of Phosphatidylcholine Hydroperoxide: Its Relevance to Ferroptosis

“…To further confirm this, we are now planning similar studies using the inhibitors of each enzyme. While our preliminary data confirmed lower degradation of PCOOH in the medium after lowering the FBS concentration to 0.3％, we would like to further evaluate this phenomenon in the future by measuring the conversion rate of PCOOH to PCOH 18) in the cell-free medium in the absence of cellular reductases. We would also like to confirm whether the prolonged exposure to GPX4 KO state in the cells may cause genetic compensation and induce the expression of other enzymes with PCOOH reducing activity.…”

The Contribution of Singlet Oxygen to Insulin Resistance

“…Similarly to the conversion of hydroperoxide (12) to dioxetane (13) ( Figure 3() ), HPNE (17) may be converted by an amine (RNH 2 ) via dioxetane (18) to MDA (19) and hexanal (20) ( Figure 4() ), thus explaining the previously reported, lysine-mediated conversion of HPNE to MDA [ 112 ]. Inorganic ferrous ion (Fe 2+ ) or organic ferric ions such as in cytochrome c (Cy-Fe 3+ ) may alternatively convert HPNE (17) to the corresponding alkoxyl radical (21), which can abstract or lose a hydrogen to form HNE (22) or ONE (23), respectively, or cyclize to form epoxyalkyl radical (24), which rearranges to oxygen-stabilized vinyl ether radical (25) [ 113 , 114 ]. The latter may react with oxygen and be converted via hydroperoxy-ether (26) and oxygen-centered radical (27) to hemiacetal (28).…”

“…The latter may react with oxygen and be converted via hydroperoxy-ether (26) and oxygen-centered radical (27) to hemiacetal (28). Vinyl ether radicals such as (25) also undergo direct conversion to hemiacetals such as (28) by oxygen rebound from the Cy-Fe 4+ −OH (or Fe 3+ −OH) pair, and the hemiacetals easily cleave to aldehydes such as MDA (19) and hexanal (20) [ 113 – 114 ].…”