|Preferred IUPAC name
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||156.225 g·mol−1|
|Boiling point||125–127 °C (257–261 °F; 398–400 K) 2 torr|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
4-Hydroxynonenal, or 4-hydroxy-2-nonenal or 4-HNE or HNE, (C9H16O2), is an α,β-unsaturated hydroxyalkenal that is produced by lipid peroxidation in cells. 4-HNE is the primary α,β-unsaturated hydroxyalkenal formed in this process. It is a colorless oil. It is found throughout animal tissues, and in higher quantities during oxidative stress due to the increase in the lipid peroxidation chain reaction, due to the increase in stress events. 4-HNE has been hypothesized to play a key role in cell signal transduction, in a variety of pathways from cell cycle events to cellular adhesion.
Early identification and characterization of 4-hydroxynonenal was reported by Esterbauer, et al., who also obtained the same compound synthetically. The topic has since been often reviewed.
4-Hydroxynonenal is generated in the oxidation of lipids containing polyunsaturated omega-6 acyl groups, such as arachidonic or linoleic groups, and of the corresponding fatty acids viz., the hydroperoxy precursors to 15-hydroxyicosatetraenoic acid and 13-hydroxyoctadecadienoic acid, respectively. Although they are the most studied ones, in the same process other oxygenated α,β-unsaturated aldehydes (OαβUAs) are generated also, which can also come from omega-3 fatty acids, such as 4-oxo-trans-2-nonenal, 4-hydroxy-trans-2-hexenal, 4-hydroperoxy-trans-2-nonenal and 4,5-epoxy-trans-2-decenal.
These compounds can be produced in cells and tissues of living organisms or in foods during processing or storage, and from these latter can be absorbed through the diet. Since 1991, OαβUAs are receiving a great deal of attention because they are being considered as possible causal agents of numerous diseases, such as chronic inflammation, neurodegenerative diseases, adult respiratory distress syndrome, atherogenesis, diabetes and different types of cancer.
There seems to be a dual and hormetic action of 4-HNE on the health of cells: lower intracellular concentrations (around 0.1-5 micromolar) seem to be beneficial to cells, promoting proliferation, differentiation, antioxidant defense and compensatory mechanism, while higher concentrations (around 10-20 micromolar) have been shown to trigger well-known toxic pathways such as the induction of caspase enzymes, the laddering of genomic DNA, the release of cytochrome c from mitochondria, with the eventual outcome of cell death (through both apoptosis and necrosis, depending on concentration). HNE has been linked in the pathology of several diseases such as Alzheimer's disease, cataract, atherosclerosis, diabetes and cancer.
The increasing trend to enrich foods with polyunsaturated acyl groups entails the potential risk of enriching the food with some OαβUAs at the same time, as has already been detected in some studies carried out in 2007. PUFA-fortified foods available on the market have been increasing since epidemiological and clinical researches have revealed possible effects of PUFA on brain development and curative and/or preventive effects on cardiovascular disease. However, PUFA are very labile and easily oxidizable, thus the maximum beneficial effects of PUFA supplements may not be obtained if they contain significant amounts of toxic OαβUAs, which as commented on above, are being considered as possible causal agents of numerous diseases.
Special attention must also be paid to cooking oils used repeatedly in caterings and households, because in those processes very high amounts of OαβUAs are generated and they can be easily absorbed through the diet.
GS-HNE is a potent inhibitor of the activity of glutathione S-transferase, and therefore must be shuttled out of the cell to allow conjugation to occur at a physiological rate. Ral-interacting GTPase activating protein (RLIP76, also known as Ral-binding protein 1), is a membrane-bound protein which has high activity towards the transport of GS-HNE from the cytoplasm to the extracellular space. This protein accounts for approximately 70% of such transport in human cell lines, while the remainder appears to be accounted for by Multidrug Resistance Protein 1 (MRP1).