Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

• Published in: Free radical biology & medicine 2017-10, Vol.111, p.294-308
• Main Authors: Sousa, Bebiana C., Pitt, Andrew R., Spickett, Corinne M.
• Format: Article
• Language: English
• Subjects: 4-hydroxy-2-hexenal; 4-hydroxy-dodecadienal; Acrolein - chemistry; Aldehydes - chemistry; Aldehydes - metabolism; Animals; Humans; Isolevuglandins; Isoprostanes - chemistry; Lactoglobulins - chemistry; Lactoglobulins - metabolism; Lipid Peroxidation; Lipoxidation; Liquid chromatography mass spectrometry; Oxidative Stress; Phospholipid oxidation; Protein Processing, Post-Translational; α,β-Unsaturated aldehydes
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2017.02.003

The process of lipid oxidation generates a diverse array of small aldehydes and carbonyl-containing compounds, which may occur in free form or esterified within phospholipids and cholesterol esters. These aldehydes mostly result from fragmentation of fatty acyl chains following radical oxidation, and the products can be subdivided into alkanals, alkenals (usually α,β-unsaturated), γ-substituted alkenals and bis-aldehydes. Isolevuglandins are non-fragmented di-carbonyl compounds derived from H2-isoprostanes, and oxidation of the ω-3-fatty acid docosahexenoic acid yield analogous 22 carbon neuroketals. Non-radical oxidation by hypochlorous acid can generate α-chlorofatty aldehydes from plasmenyl phospholipids. Most of these compounds are reactive and have generally been considered as toxic products of a deleterious process. The reactivity is especially high for the α,β-unsaturated alkenals, such as acrolein and crotonaldehyde, and for γ-substituted alkenals, of which 4-hydroxy-2-nonenal and 4-oxo-2-nonenal are best known. Nevertheless, in recent years several previously neglected aldehydes have been investigated and also found to have significant reactivity and biological effects; notable examples are 4-hydroxy-2-hexenal and 4-hydroxy-dodecadienal. This has led to substantial interest in the biological effects of all of these lipid oxidation products and their roles in disease, including proposals that HNE is a second messenger or signalling molecule. However, it is becoming clear that many of the effects elicited by these compounds relate to their propensity for forming adducts with nucleophilic groups on proteins, DNA and specific phospholipids. This emphasizes the need for good analytical methods, not just for free lipid oxidation products but also for the resulting adducts with biomolecules. The most informative methods are those utilizing HPLC separations and mass spectrometry, although analysis of the wide variety of possible adducts is very challenging. Nevertheless, evidence for the occurrence of lipid-derived aldehyde adducts in biological and clinical samples is building, and offers an exciting area of future research. [Display omitted] •Oxidative lipid fragmentation generates a complex family of reactive aldehydes.•Acrolein, 4-hydroxyhexenal, and 4-hydroxynonenal are highly reactive & abundant.•Large inter-study variability observed in free aldehyde levels in human plasma.•Aldehyde biological effects depend on adduct formation with cellular macrom