Oxidized Phospholipids


1.  Introduction

During conditions of oxidative stress and redox imbalance, reactive oxygen species (ROS), such as the superoxide anion (O2•-), hydroxyl radical (OH), nitric oxide (NO) and peroxyl radicals (LOO), can be generated in cells. To these can be added non-radical oxidizing agents such as hydrogen peroxide (H2O2), hypochlorous acid (HOCl), ozone (O3), and singlet oxygen (1O2). They can be formed in animal and plant tissues from such external sources as UV radiation or internally as byproducts of mitochondrial processes, for example, and they can then attack lipid-bound unsaturated fatty acids by non-enzymatic mechanisms (autoxidation). In particular, the phospholipids in lipid membranes provide a readily accessible platform where the effects of ROS are amplified at every step through a cascade of chemical reactions.

The result is the formation initially of many different lipid-bound fatty acyl hydroperoxides, the primary peroxidation products, which can react further to produce innumerable secondary oxygenated metabolites, with hydroxyl, epoxy or oxo groups, often as short-chain fragments with reactive electrophilic carbonyl moieties that can exert specific biological effects. In addition, a peroxyl radical can react intramolecularly to form an endoperoxide in which the molecule retains an unpaired electron, and can rearrange to form 5-membered ring structures, such as the cyclopentenone rings in isoprostanes. Oxidized lipids in the circulation and in cell membranes can have both beneficial and harmful effects on the human body. Excessive amounts of oxidized phospholipid products have been linked to the pathogenesis of various cardiopulmonary disorders, such as atherosclerosis and thrombosis, acute lung injury and neurodegenerative processes, while beneficial effects include the induction of anti-inflammatory mediators. Accumulation of lipid hydroperoxides is central to a recently identified form of cell death known as ferroptosis.

Oxidized forms of polyunsaturated fatty acids

Oxidized lipids formed by enzymatic reactions add complexity to the picture. The chemistry, biochemistry, pharmacology, and molecular biology of those oxidized fatty acids formed by mainly enzymatic means and covered by the generic term oxylipin, including eicosanoids, docosanoids and plant oxylipins, are important subjects that are described in many web pages in our section on Fatty Acids and Oxylipins. While much work has been concerned with the bio-activity of these in unesterified form, it is increasingly being recognized that intact oxidized lipids, i.e. phospholipids, cholesterol esters and others containing such oxylipins, can have profound biological effects in tissues of both animals and plants. Cellular systems must maintain a balance between pro-oxidants formation and antioxidant defenses if oxidative stress is to be avoided. The varied nature of the oxidation products from the two types of reaction mean that the effects are highly complex and often apparently contradictory, so only a general flavour of the topic is possible here.

While phospholipids containing intact fatty acids with oxygen moieties in the chain have great biological relevance, technical difficulties in analysis may explain why research has lagged behind that of the cleavage products of hydroperoxides, i.e. volatile aldehydes, which are especially important for any discussion of the biological effects of oxidized lipids and have their own web page. The isoprostanes formed by non-enzymatic oxidation reactions of fatty acids in esterified form must be considered in the same context, as do the formation and properties of esterified hydroperoxy- and hydroxy-eicosatetraenoic acids (HETE) produced enzymatically, oxidized sterols and cholesterol esters, and esterified plant oxylipins, for example. Similarly, nitrated phospholipids are relevant to this topic and are discussed in a separate web page.


2.  Autoxidation

Radical Reactions: All polyunsaturated fatty acids can undergo autoxidation by free radical chain-reaction mechanisms as discussed in several web pages on this website, including those dealing the antioxidant properties of tocopherols and coenzyme Q, which are key elements of the defense against oxidative damage to cells. To summarize briefly, autoxidation consists of three main steps: initiation, propagation and termination. The initiation step begins with abstraction of a hydrogen atom by a ROS from the bis-allylic carbon of one of the 1,4‑cis,cis‑pentadiene moieties of a polyunsaturated fatty acid, with formation of a carbon-centred radical, which tends to be stabilized through resonance by a molecular rearrangement to form a conjugated diene (usually trans-cis). The peroxidation rate is very low in the absence of catalysts but is greatly enhanced by transition metals and especially by iron (Fe). Normally, the levels of free Fe-ions are strictly controlled in cells by binding to specific proteins, but when there is an Fe-overload or poorly controlled Fe-protein complexes, aberrant non-enzymatic lipid peroxidation can accelerate rapidly.

Autoxidation of arachidonic acid

This initial step is followed by the propagation and rate determining step in which the unstable fatty acid radical reacts with molecular oxygen to generate a peroxyl radical; this propagates the chain reaction by abstracting a hydrogen atom from another unsaturated fatty acid to produce a lipid hydroperoxide and another reactive lipid peroxyl radical, which is the chain carrier of lipid autoxidation (and is the source of the volatile aldehydes). Such reactions have limited positional and no stereo specificity, and it is illustrated here for one only of the possible reactions of arachidonate.

Termination of the process occurs when two radicals interact to produce dimeric products. However, this is a relatively rare occurrence, and it is much more usual for a radical-trapping antioxidant, such as α-tocopherol, to break the chain reaction and prevent further oxidation of polyunsaturated fatty acids. As a final detoxification step, reduction to the chemically less reactive lipid hydroxide occurs, catalysed by a reductase such as glutathione peroxidase 4 (GPx4), which acts preferentially upon lipid hydroperoxides and is one of a family of selenium-containing enzymes that utilize glutathione as a substrate; this enzyme is of special importance in ferroptosis (see below). In this example, the product is a hydroxy-eicosatetraenoic acid (HETE) esterified to the lipid.

Many mono-hydroperoxy isomers of arachidonic acid other than that illustrated are produced, and similar reactions occur during the formation of ring-containing isoprostanes, i.e. with cyclopentenone or endoperoxide structures, which can be cleaved to form isolevuglandins. If the comparable autoxidation reactions of linoleate, linolenate, eicosapentaenoate (EPA) and docosahexaenoate (DHA) by such mechanisms are taken into consideration, together with the lack of stereochemical control and the probable formation of dihydroperoxides, the range of possible hydroperoxy and other oxygenated products is enormous.

Singlet oxygen: Ene reaction of singlet oxygenGround-state or triplet molecular oxygen (O2) is a paramagnetic biradical bearing two valence electrons with parallel spins, and this prevents spontaneous reaction with non-radical molecules at ambient temperatures. On the other hand, electronically excited or singlet oxygen (1O2 or O=O), in which the spin of one of the unpaired electrons is changed to yield two electrons with opposite spins, is capable of oxidizing non-radical organic molecules. With double bonds, singlet oxygen acts via an ene-reaction to yield fatty acyl hydroperoxides, which can react further as described above and add to the complexity of the oxidized products.

Singlet oxygen can be produced endogenously in various ways. For example, during the chain termination step of autoxidation, it is formed by the self-reaction of lipid peroxyl radicals, or it may be generated through photo-sensitization, i.e. the interaction of UV or visible light with natural chromophores, e.g. riboflavins, porphyrins, bilirubin or melanin, normally present in cells. These act to donate energy to molecular oxygen to produce singlet oxygen, which can then attack DNA bases, proteins and double bonds in polyunsaturated fatty acids. The head groups of phospho- and glycolipids can also be attacked, and for example photooxidation of phosphatidylethanolamine can lead to the formation of phosphatidic acid.

The reaction with singlet oxygen is utilized for the benefit of patients with cancer, macular degeneration and microbial infections by means of photodynamic therapy in which singlet oxygen is generated in a controlled manner by the action of light on exogenous photosensitizers that have been delivered to target cells. A directed light dose generates sufficient hydroperoxides to destroy these cells with a minimum of peripheral damage.


3.  Phospholipids containing Oxylipins formed Enzymatically

Fatty acids are oxidized to hydroperoxy fatty acids in animal and plant tissues by several different lipoxygenases and cytochrome P450 enzymes, which produce products with a high degree of positional and stereospecificity. These reactions in animals are discussed in our web page dealing with hydroxyeicosatetraenes (HETE), and while they occur mainly on unesterified polyunsaturated fatty acids such as arachidonate, most of the oxidation products can be esterified subsequently by the enzymes of the Lands' cycle, mainly to phosphatidylethanolamine. However, the 15- and 12/15‑lipoxygenases are able to oxidize phospholipid-bound fatty acids directly. The result is a relatively restricted range of products that are formed through controlled pathways, especially in innate immune cells. Even so, at least 100 unique oxidized phospholipids of this type have been identified, mainly of phosphatidylethanolamine, but also of phosphatidylcholine with much fewer of phosphatidylinositol.

Circulating innate immune cells and platelets generate phospholipids containing oxylipins by coordinated signalling pathways mediated by receptor-dependent calcium mobilization. Two main mechanisms have been described in these circumstances. In the first, membrane phospholipids, mainly phosphatidylcholine and phosphatidylethanolamine, are hydrolysed by a phospholipase A2 (PLA2) to release arachidonic acid from position sn-2 to be acted upon by COX or LOX enzymes to produce oxidized forms. These can be activated by an acyl-coenzyme A synthase (ACS) and esterified to position sn-2 of a lysophospholipid with a saturated fatty acid in position sn-1 by an sn-2 acyltransferase.

Biosynthesis of oxidized phospholipids

In the second pathway, the fatty acid in position sn-1 of a phospholipid is removed by a phospholipase (iPLA2γ, the main phospholipase in mitochondria), which is selective for the fatty acid in position sn-1, to leave a lysophospholipid containing arachidonic acid in position sn-2. Cytochrome c is a plasmalogenase and may generate 2-arachidonoyl-lysophospholipids from plasmalogens under conditions of oxidative stress. The products can act as substrates for oxidizing enzymes such as human platelet-type 12-lipoxygenase (12-LOX) or the 15‑lipoxygenase. The lysophospholipids 12(S)‑HETE‑lysophosphatidylcholine and 12(S)‑HETE‑lysophosphatidylethanolamine are biological mediators per se, but they can also be selectively esterified in position sn-1 by a saturated fatty acid by means of an sn-1 acyltransferase. It has been established that the second pathway is markedly activated by calcium ionophore (A23187) or thrombin treatment of murine platelets to generate oxidized lysophospholipids or phosphatidylcholine, respectively. Under conditions of oxidative stress, 15-lipoxygenase and secreted phospholipase A2 act synergistically to form various oxidized lysophospholipids, including hydroxy, hydroperoxy, and keto products of 2-arachidonoyl-lysophosphatidylinositol, which are endogenous agonists for Toll-like receptor 4 (TLR4) with adverse effect upon patients with rheumatoid arthritis and gout.

On cellular activation, approximately 30% of the 12-HETE generated by human platelets is esterified into these lipids at pico- to nanomole levels at the same rate as for the synthesis of free 12-HETE. Some may be formed by direct oxidation of intact phospholipids, for example by the action of 15-LOX in human monocytes (or murine 12/15-LOX), but most is produced by subsequent esterification of free oxylipins. This has lead to the suggestion that the various biosynthetic enzymes are colocalized and work cooperatively, and it is certain that there is great selectivity towards the substrates and the oxidation products that are generated. Some of these esterified lipoxygenase products of phospholipids are believed to remain within the membranes where they may serve as a storage form to be released on appropriate stimulation, possibly into other cellular compartments with different biological roles from their unesterified equivalents.


4.   Oxidatively Truncated Phospholipids

Instead of the final reductive step in autoxidation, fission of hydroperoxides can occur with aldehyde generation by oxidative cleavage via a variety of mainly non-enzymatic mechanisms, and via epoxy and dioxetane intermediates to give many different aldehydes from each hydroperoxide, as discussed at length in our web page on bioactive aldehydes. A corollary of this process is that a fragment of the oxidized molecule remains esterified to the original phospholipid, i.e. as oxidized phospholipids, which can originate from both enzymic and non-enzymic precursors. These are sometimes termed 'core aldehydes' or 'oxidatively truncated' phospholipids and are also discussed briefly in our web page dealing with platelet-activating factor, as this and oxidatively truncated phosphatidylcholine have some properties in common. These oxidized phospholipids can be metabolized subsequently by enzymes of the aldoketoreductase family to produce alcohols or by the aldehyde dehydrogenase family to generate carboxylic acids, resulting in further product diversity and biological activities. Similar oxidized forms of cardiolipin, phosphatidylserine and phosphatidylethanolamine have been studied also.

It is now evident that the lipid-bound fragments resulting from oxidative cleavage can exert profound biological effects towards inflammation, infection and the immune response in animal tissues. As an example, phosphatidylcholine is the most abundant phospholipid in most animal cells, and it is not recognized by any pattern-recognition receptors in native low-density lipoproteins (LDL) or on the surface of cells. However, an oxidized species such as 1-palmitoyl-2-(5‑oxovaleroyl)-sn-glycero-3-phosphocholine in oxidized LDL and on apoptotic cells is a key ligand that mediates the binding of oxidized LDL to the receptor CD36 and scavenger receptor class B type I (SR-B1), and this is important for the formation of foam cells. Such oxidized phospholipids inhibit uptake of cholesterol esters by SR-BI on liver cells, and by this means impair reverse cholesterol transport.

Formula of 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine

Once formed, an immediate effect is membrane disruption with increased permeabilization, while formation of covalent adducts with membrane proteins can further damage membrane integrity. When there is a double bond in the truncated remnant, i.e. to form a γ-oxoalkenal phospholipid, the molecule is especially reactive and for example, it can selectively interact to cross-link apolipoprotein A1 in high-density lipoproteins (HDL) in plasma (Michael addition). This impairs the cholesterol efflux mediated by apoA1 and may contribute to the loss of the atheroprotective function of HDL in vivo. For example, inflammatory pathways can be inhibited by activation of the peroxisome proliferator-activated receptor (PPARγ) for which the sn-1 alkyl phospholipid hexadecyl-2-azelaoyl-phosphatidylcholine is a specific and high-affinity ligand.

It should be noted that hundreds of such oxidized lipid species are formed in tissues of all kinds under innumerable physiological conditions, but the biological properties of only a handful of model compounds have been studied in any detail. On the other hand, fewer molecular species are often observed in vivo than might be expected from experiments in vitro. Oxidized lipids of this kind have a tendency to accumulate in tissues of the elderly, especially in the lung, where they can potentiate the induction of damaging inflammatory agents.

Oxidatively truncated phospholipids can be degraded by the platelet-activating factor-acetylhydrolase and a lysosomal phospholipase A2, and the aldehydo-acid component released in this way can participate in biological reactions as discussed in our web page on bioactive aldehydes.


5.  Biological Effects of Oxidized Phospholipids

Many effects of oxidized phospholipids may be exerted through the perturbation of the structures of cellular membranes, as they tend to introduce deformation by producing an increase in membrane surface area and a decrease in membrane thickness. This can result in impairment of barrier function, increased membrane permeability leading to pore formation, and an elevated flip-flop rate. However, in general, membrane integrity is not compromised unless excessive hydroperoxidation occurs as in ferroptosis. As oxidatively modified acyl chains are believed to protrude into the aqueous medium, they are more accessible for participation in signalling events including macrophage recognition. The electrophilic characteristics of some of these molecules, which can include hydroperoxides, hydroxides, keto groups and epoxides, can promote adduct formation with membrane proteins leading to further disruption to membranes as well as to direct effects upon enzyme function. While much research has been concentrated on oxidation of the unsaturated acyl moieties in phospholipids, the polar head groups can also be affected, and as an example, oxidative deamination of phosphatidylserine can produce glycero-3-phosphoacetic acid with subsequent effects upon membrane structure and perhaps signalling.

Those oxidized phospholipids generated non-enzymatically by free radical mechanisms tend to be very different from those formed by enzymic oxidation, especially in that a much wider range of isomeric products is formed. They are generally if not universally considered harmful because they contribute to autoimmune and inflammatory diseases and cell death. The complex nature of the products formed with different lipids and proteins often means that it is not easy to delineate the detailed mechanisms behind such effects, or whether the effects are due to molecules containing intact oxidized fatty acids or those that are oxidatively truncated.

Some highly specific activities of oxidized phospholipids are discussed in relation to particular phospholipid classes elsewhere on this website. Oxidized phosphatidylserine is an important aspect of the mechanism of apoptosis (programmed cell death), while oxidized cardiolipin acts as a required signal for the execution of the intrinsic apoptotic programme (mitophagy) in mitochondria.

Inflammation: A body of evidence has accumulated to indicate that oxidized phospholipids have a role in promoting various acute and chronic inflammatory diseases, including atherosclerosis, microbial infections, lung injury and neurodegenerative diseases. As some other studies suggest anti-inflammatory activities, it is apparent that a complex range of mechanisms is involved. For example, during oxidative stress in vivo, low-density lipoproteins (LDL) especially are enriched in oxidized phospholipids and these can react with the apoproteins to increase the atherogenic potential of LDL with deleterious effects on cardiovascular disease (see our web page on lipoproteins). Oxidized phospholipids in excess in the circulation are considered to be biomarkers of atherosclerosis, and oxidized phosphatidylcholine bound to lipoproteins containing apoB-100 is reported to be a biomarker for calcific aortic valve stenosis, stroke and coronary events. An antibody termed E06 has been developed in transgenic mice that blocks many biological effects of oxidized phosphatidylcholine in experimental models of acute and chronic inflammation including atherosclerosis, ischemia-reperfusion injury and steatohepatitis. In addition, oxidized phospholipids stimulate specific binding of endothelial cells to monocytes, and this is believed to trigger vascular inflammation and formation of atherosclerotic plaques with activation of inflammatory mediators such as the transcription factor nuclear factor (erythrocyte-derived 2)-like 2 (Nrf2). Therefore, it has become apparent that oxidized phospholipids are not merely markers of pathological conditions but play a causative role in the initiation and progression of diseases.

In inflamed tissue, oxidized phospholipids act as endogenous pain-inducing metabolites, which excite sensory, nociceptive neurons by activating transient receptor potential ion channels, specifically TRPA1 and TRPV1. They are intimately involved in the progression of chronic obstructive pulmonary disease (COPD), a common lung disease characterized by an increased chronic inflammatory leading to persistent airflow limitation, and they have been implicated in the response to traumatic brain injury, Alzheimer disease and Parkinson’s disease, while in the eye, they are a factor in age-related macular degeneration. Further, they are believed to be involved in some diseases of the liver and kidney, diabetes, autoimmune disease, and possibly cancer (via immunosuppressive effects).

Scottish thistleOther biological effects of oxidized phospholipids may be mediated via specific receptors. A concept has been developed of the formation of damage(or danger)-associated molecular patterns (DAMPs) that arise from the controlled oxidation of lipids and lipoproteins. Those DAMPs derived by oxidation share common structural motifs with microbial pathogen-associated molecular patterns and so activate the same pattern-recognition receptors that are present on the surface of macrophages and of immune and vascular cells, and so they initiate many different inflammatory signalling processes by induction of chemokines and proinflammatory cell adhesion molecules. For example, mono-acyl phospholipids such as 2-12(S)-HETE-lysophospholipids, like non-esterified 12(S)-HETE, are potent and specific lipid mediators that activate THP‑1 human monocytic cells to generate tumor necrosis factor α (TNFα) and interleukin 8 (IL8) at nanomolar concentrations to promote inflammatory cascades. Phosphatidylcholine containing an epoxyisoprostane residues is able to activate the prostanoid receptors EP2 and DP with proinflammatory effects.

On the other hand, the effects of oxidized phospholipids need not always be deleterious, as they can lead to inhibition of acute inflammation by activating anti-inflammatory pathways to attenuate the deleterious effects. It has been suggested that oxidized lipids at lower concentrations may prime the receptors that respond to bacterial infection to activate dendritic and T cells resulting in enhanced protection. After acute activation by bacteria or bacterial products, neutrophils generate 5-HETE-containing phospholipids by 5-lipoxygenase (5-LOX) reaction, while macrophages and monocytes generate similar phospholipids through 15‑LOX and 12/15‑LOX activity. 12- and 15-Keto-eicosanoic acids attached to phosphatidylethanolamine are known to activate PPARγ, for example. Binding of such oxidized phospholipids to the receptors that recognize bacterial toxins can result in complete inhibition of the proinflammatory action of lipopolysaccharides during infections, thereby eliminating the worst effects of TLR4-mediated inflammatory signalling and the expression of cytokines. Oxidized phospholipids of this kind generated in the outer leaflet of the plasma membrane in platelets and leukocytes can also promote the activity of clotting factors and promote blood coagulation following tissue injury to limit bleeding while simultaneously inhibiting infection. In addition, the phospholipid products of 15-LOX have a vial function towards the resolution of inflammation. Increased levels of oxidation products in the lung improve recovery by facilitating the production of the anti-inflammatory lipid mediator, lipoxin A4, and other related molecules.


6.  Ferroptosis

Ferroptosis is an often pathological form of cell death that is genetically and biochemically distinct from apoptosis per se in that it is not activated by caspases, and pore-forming or functionally related proteins. Rather, it is dependent on iron and is characterized by the accumulation of lipid peroxides derived from polyunsaturated fatty acids to such an extent that cellular membranes are disrupted. The oxidized phospholipids that induce ferroptosis may be formed both by non-enzymatic autoxidation and by enzymic means. For example, oxidoreductases, including NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase (CYB5R1), transfer electrons from NAD(P)H to oxygen to generate hydrogen peroxide, which can reacts with iron to generate reactive hydroxyl radicals. In addition, hydroperoxy-derivatives of arachidonoyl- or adrenoyl-phosphatidylethanolamines (20:4(n-6) and 22:4(n-6)), which are generated by 15‑lipoxygenase, are reported to have a specific involvement in ferroptosis. The nature and concentrations of ferric ions (Fe3+) and ferrous ions (Fe2+) in cellular compartments are crucial. Within the endosomal compartments of the cell, ferric ions are reduced to ferrous ions and released into a labile iron pool in the cytoplasm via the divalent metal transporter 1 (DMT1), where it may be stored in complexation with the protein ferritin. Any disturbances in iron uptake or storage contribute to iron overload, and this has the potential to generate highly reactive hydroxyl radicals through the Fenton reaction (see our web page on isoprostanes, for example). These radicals can oxidize the polyunsaturated fatty acids in the phospholipids of membranes to generate hydroperoxides and induce ferroptosis when insufficient levels of antioxidants or antioxidant enzymes are available.

Ferroptosis manifests itself as necrotic changes that include cell enlargement, swelling of some organelles but shrinkage of mitochondria, and membrane rupture. While this can be an essential process for maintaining cellular homeostasis, dysfunctional ferroptosis can be a cause of disease and pathological conditions. For example, it can promote inflammatory diseases and assist the invasion of host cells by bacterial pathogens. Ferroptosis is currently a subject of intensive study, as it has been shown to be involved in cell death associated with Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, cancer, kidney degradation and myocardial ischemia-reperfusion injury.

By converting lipid hydroperoxides into non-toxic lipid alcohols, the glutathione peroxidase 4 (GPx4) prevents ferroptosis with assistance from the ferroptosis suppressor protein 1 (FSP1) and ubiquinone (coenzyme Q). Glutathione deficiency and/or inhibition of GPx4 function lead to lipid peroxide formation and to the induction of ferroptosis. In addition, the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is essential for the regulation of the antioxidant response in animal cells, as it controls the expression of antioxidant or cytoprotective genes that act against oxidative stresses such as ferroptosis. This has become a key target in the development of anti-cancer therapies, as well as for the prevention of neurodegenerative and cardiovascular diseases. In addition, cells can initiate mechanisms to repair or to isolate and remove damaged membranes. Activation of the ESCRT-III (endosomal sorting complex required for transport-III) machinery, for example, leads to membrane repair by shedding damaged parts of the cell membrane and so prevents various types of lytic cell death, including ferroptosis.


7.  Oxidized Glycerolipids in plants

Intact phospholipids and glycosyldiacylglycerols containing oxidized lipids are produced in plants by similar mechanisms to those in animal tissues, and plants have developed appropriate antioxidant defenses. As in animals, reactive oxygen species (ROS) are produced as a natural byproduct of normal metabolism in plant cells, but especially in the apoplast, mitochondria, chloroplasts, and peroxisomes, and these can react with DNA, lipids and proteins to at worst cause cellular death. Under normal circumstances, a steady state is reached between generation and elimination of ROS, but this balance can be disturbed by biotic and abiotic stresses of all kinds, but especially, by light intensity, UV-B radiation and temperature extremes. Processes similar to ferroptosis in animals have been observed in plants also.

Free radical oxidation by all the reactants described above can occur in plants, but superoxide anions (O2•-) are of special importance, as they can be produced during photosynthetic electron transport in chloroplasts. Similarly, singlet oxidation is generated during photosynthesis by both photosystems (PSI and PSII). Formation of bioactive aldehydes is a key reaction, as discussed on that web page, and they have vital biological functions. These rather than intact lipid peroxides have been the focus of most research, although the latter can accumulate in plants under conditions of abiotic stress, and for example, salt-induced oxidative damage to membrane lipids can be used as an indicator of tolerance to salt stress in barley roots.

However, those oxidized lipids produced by enzymatic reaction are of increasing interest, and they are described in our web page on plant oxylipins. The best known of these lipids are the arabidopsides, glycosyldiacylglycerols containing jasmonate precursors, which are produced rapidly in the membranes of leaves under stress. It seems probable that they serve as a reservoir of oxylipins to be called upon when required. Similarly, colneleic and colnelenic acids are produced quickly via the action of 9-lipoxygenase in leaves of potato plants infected by bacteria, fungi or viruses, and have been found esterified at the sn-2 position of phospholipids, i.e. as a preformed pool that is available immediately in response to challenge by pathogens such as potato blight.

The effects of all oxidized lipids are countered by active antioxidative systems, including endogenous antioxidants such as ascorbic acid, glutathione, α‑tocopherol, carotenoids, flavonoids and plastoquinone, together with enzymatic systems, such as superoxide dismutase, catalase, ascorbate peroxidase and other peroxidases, and various reductases.


8.  Analysis

Oxidized phospholipids are now more easily analysed by modern lipidomics methodology than was possible earlier, and this is leading to increasing research on the topic. Although adduct formation between oxidized lipids and proteins remains a technical analytical challenge, it is one that appears to be surmountable.


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Lipid listings Credits/disclaimer Updated: July 15th, 2021 Author: William W. Christie LipidWeb icon