Chlorinated Phospholipids and Fatty Acids: (Patho)physiological Relevance, Potential Toxicity, and Analysis of Lipid Chlorohydrins

Abstract

Chlorinated phospholipids are formed by the reaction of hypochlorous acid (HOCl), generated by the enzyme myeloperoxidase under inflammatory conditions, and the unsaturated fatty acyl residues or the head group. In the first case the generated chlorohydrins are both proinflammatory and cytotoxic, thus having a significant impact on the structures of biomembranes. The latter case leads to chloramines, the properties of which are by far less well understood. Since HOCl is also widely used as a disinfecting and antibacterial agent in medicinal, industrial, and domestic applications, it may represent an additional source of danger in the case of abuse or mishandling. This review discusses the reaction behavior of in vivo generated HOCl and biomolecules like DNA, proteins, and carbohydrates but will focus on phospholipids. Not only the beneficial and pathological (toxic) effects of chlorinated lipids but also the importance of these chlorinated species is discussed. Some selected cleavage products of (chlorinated) phospholipids and plasmalogens such as lysophospholipids, (chlorinated) free fatty acids and α-chloro fatty aldehydes, which are all well known to massively contribute to inflammatory diseases associated with oxidative stress, will be also discussed. Finally, common analytical methods to study these compounds will be reviewed with focus on mass spectrometric techniques.

Recent Developments of Useful MALDI Matrices for the Mass Spectrometric Characterization of Lipids

“…Usually, the related analyses are performed by ESI MS [98] because this technique is somewhat softer than the MALDI and, thus, the detection of labile species (such as, hydroperoxides) is improved [99]. Lipid peroxidation products and oxidation products generated by hypochlorous acid (HOCl), an important oxidant generated, particularly, under inflammatory conditions [100], which adds to the unsaturated fatty acyl residues of lipids (leading to the generation of chlorohydrins and products derived, thereof [101]) are readily detectable in the presence of DHB [102], as well as other common matrices. The detection of other oxidation/chlorination products is a more challenging task.…”

Phospholipases and Reactive Oxygen Species Derived Lipid Biomarkers in Healthy and Diseased Humans and Animals – A Focus on Lysophosphatidylcholine

“…This is the precursor for the generation of further, much more reactive species, for instance, hydroxyl radicals (HO • ). Despite the high reactivity of HO • , that reacts diffusion-controlled with nearly all organic molecules, another ROS seems to be responsible for the increased levels of LPC under pathological conditions: hypochlorous acid (HOCl; Schröter and Schiller, 2016 ). HOCl is generated under in vivo conditions from H 2 O 2 and Cl – ions under catalysis of myeloperoxidase (MPO; Kargapolova et al, 2021 ):…”

“…Myeloperoxidase is nearly exclusively found in neutrophils, where it amounts to approximately 5% of the total protein content ( Schröter and Schiller, 2016 ). As the number of neutrophilic granulocytes increases massively under inflammatory conditions, the roles of MPO and its products are obvious ( Arnhold, 2020 ).…”

Effects of exposure to water disinfection by-products in a swimming pool: A metabolome-wide association study

“…Interestingly, the mass difference of two of the compounds corresponded to that of hypochlorous acid (HOCl), which is the hydration product of Cl 2 and one of the primary disinfection agents of chlorine solutions. HOCl is reactive with a number of biomolecules in vivo and ex vivo , including fatty acids, lipids and aromatic amino acids and different chlorinated metabolites are known to form after chlorine exposure ( Fu et al, 2000 , Hazen et al, 1996 , Schroter and Schiller, 2016 ). The two compounds could thus be two reaction products after an addition of HOCl or Cl 2 to a double bond of a compound R to yield HO-R-Cl and Cl 2 -R, or the mono- and dichlorinated products of two compounds HO-R and R through aromatic substitution.…”