Lipid peroxidation, or lipid oxidation, is a complex

chemical process In a scientific sense, a chemical process is a method or means of somehow changing one or more chemicals or chemical compounds. Such a chemical process can occur by itself or be caused by an outside force, and involves a chemical reaction of som ...

that leads to oxidative degradation of

lipids Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...

, resulting in the formation of

peroxide In chemistry, peroxides are a group of Chemical compound, compounds with the structure , where the R's represent a radical (a portion of a complete molecule; not necessarily a free radical) and O's are single oxygen atoms. Oxygen atoms are joined ...

and

hydroperoxide Hydroperoxides or peroxols are Chemical compound, compounds of the form ROOH, where R stands for any group, typically Organic compound, organic, which contain the hydroperoxy functional group (). Hydroperoxide also refers to the hydroperoxide anio ...

derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz , first2=Mario F. , last3=Argüelles , first3=Sandro , date=2014 , title=Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal , journal=Oxidative Medicine and Cellular Longevity , language=en , volume=2014 , pages=1–31 , doi=10.1155/2014/360438 , doi-access=free , issn=1942-0900 , pmc=4066722 , pmid=24999379 It occurs when

free radicals In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired electron, unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemical reaction, chemi ...

, specifically

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS), interact with lipids within

cell membranes The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...

, typically

polyunsaturated fatty acids In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid (abbreviated PUFA), which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsa ...

(PUFAs) as they have carbon–carbon double bonds. This reaction leads to the formation of lipid radicals, collectively referred to as lipid peroxides or lipid oxidation products (LOPs), which in turn react with other

oxidizing agents An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ''electron donor''). In ot ...

, leading to a

chain reaction A chain reaction is a sequence of reactions where a reactive product or by-product causes additional reactions to take place. In a chain reaction, positive feedback leads to a self-amplifying chain of events. Chain reactions are one way that sys ...

that results in

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

and

cell damage Cell damage (also known as cell injury) is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. Amongst other causes, this can be due to physical, chemical, infectious, biological, nutrition ...

. In

pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...

and

medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

, lipid peroxidation plays a role in cell damage which has broadly been implicated in the

pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...

of various diseases and disease states, including

ageing Ageing (or aging in American English) is the process of becoming older until death. The term refers mainly to humans, many other animals, and fungi; whereas for example, bacteria, perennial plants and some simple animals are potentially biol ...

,{{Cite journal , last=Nam , first=Tae-Gyu , date=2011-03-01 , title=Lipid Peroxidation and Its Toxicological Implications , journal=Toxicological Research , language=en , volume=27 , issue=1 , pages=1–6 , doi=10.5487/TR.2011.27.1.001 , issn=1976-8257 , pmc=3834518 , pmid=24278542{{cite journal , last1=Porter , first1=Ned A. , last2=Caldwell , first2=Sarah E. , last3=Mills , first3=Karen A. , date=1995 , title=Mechanisms of free radical oxidation of unsaturated lipids , journal=Lipids , volume=30 , issue=4 , pages=277–290 , doi=10.1007/BF02536034 , pmid=7609594 , s2cid=4051766 whereas in

food science Food science (or bromatology) is the basic science and applied science of food; its scope starts at overlap with agricultural science and nutritional science and leads through the scientific aspects of food safety and food processing, informing ...

lipid peroxidation is one of many pathways to

rancidity Rancidification is the process of complete or incomplete autoxidation or hydrolysis of fats and oils when exposed to air, light, moisture, or bacterial action, producing short-chain aldehydes, ketones and free fatty acids. When these processes ...

Reaction mechanism

The

chemical reaction A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...

of lipid peroxidation consists of three phases: ''initiation'', ''propagation'', and ''termination''. In the ''initiation'' phase, a

pro-oxidant Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example, an overdose of ...

hydroxyl radical The hydroxyl radical, •HO, is the neutral form of the hydroxide ion (HO–). Hydroxyl radicals are highly reactive and consequently short-lived; however, they form an important part of radical chemistry. Most notably hydroxyl radicals are pr ...

({{chem2, OH•)

abstracts An abstract is a brief summary of a research article, thesis, review, conference proceeding, or any in-depth analysis of a particular subject and is often used to help the reader quickly ascertain the paper's purpose. When used, an abstract always ...

the

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

at the

allylic In organic chemistry, an allyl group is a substituent with the structural formula . It consists of a methylene bridge () attached to a vinyl group (). The name is derived from the scientific name for garlic, . In 1844, Theodor Wertheim isolat ...

position (–CH₂–CH=CH₂) or methine bridge (=CH−){{Clarification needed, reason=Is a methine bridge synonymous here with the bis-allylic or allylic position?, date=March 2024 on the stable lipid substrate, typically a

polyunsaturated fatty acid In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid (abbreviated PUFA), which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsa ...

(PUFA), to form the lipid radical ({{Chem2, L•) and water (H₂O). In the ''propagation'' phase, the lipid radical ({{Chem2, L•) reacts with

molecular oxygen There are several known allotropes of oxygen. The most familiar is molecular oxygen (), present at significant levels in Earth's atmosphere and also known as dioxygen or triplet oxygen. Another is the highly reactive ozone (). Others are: * Atomic ...

({{Chem2, O2) to form a lipid hydroperoxyl radical ({{Chem2, LOO•). The lipid hydroperoxyl radical ({{Chem2, LOO•) can further abstract hydrogen from a new PUFA substrate, forming another lipid radical ({{Chem2, L•) and now finally a lipid

(LOOH).{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz , first2=Mario F. , last3=Argüelles , first3=Sandro , date=2014-05-08 , title=Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal , journal=Oxidative Medicine and Cellular Longevity , language=en , volume=2014 , pages=e360438 , doi=10.1155/2014/360438 , doi-access=free , issn=1942-0900 , pmc=4066722 , pmid=24999379 The lipid hydroperoxyl radical ({{Chem2, LOO•) can also undergo a variety of reactions to produce new radicals.{{Citation needed, date=March 2024 The additional lipid radical ({{Chem2, L•) continues the

, whilst the lipid hydroperoxide (LOOH) is the primary end product. The formation of lipid radicals is sensitive to the

kinetic isotope effect In physical organic chemistry, a kinetic isotope effect (KIE) is the change in the reaction rate of a chemical reaction when one of the atoms in the reactants is replaced by one of its isotopes. Formally, it is the ratio of rate constants for t ...

Reinforced lipids Reinforced lipids are lipid molecules in which some of the fatty acids contain deuterium. They can be used for the protection of living cells by slowing the chain reaction due to isotope effect on lipid peroxidation. The lipid bilayer of the cel ...

in the membrane can suppress the chain reaction of lipid peroxidation. The ''termination'' step can vary, in both its actual chemical reaction and when it will occur. Lipid peroxidation is a self-propagating chain reaction and will proceed until the lipid substrate is consumed and the last two remaining radicals combine, or a reaction which terminates it occurs. Termination can occur when two lipid hydroperoxyl radicals ({{Chem2, LOO•) react to form

and oxygen (O₂).{{Clarification needed, reason=True?, date=March 2024 Termination can also occur when the concentration of radical

species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...

is high.{{Citation needed, date=March 2024 The primary products of lipid peroxidation are lipid hydroperoxides (LOOH).

Arachidonic acid as a substrate

When

arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

is a substrate, isomers of hydroperoxyeicosatetraenoic acid (HPETEs) and hydroxyeicosatetraenoic acids (HETEs) are formed.{{Citation needed, date=March 2024

Role of antioxidants

{{Main, Antioxidants Free Radical Toxicity

Antioxidants play a crucial role in mitigating lipid peroxidation by neutralizing free radicals, thereby halting radical chain reactions. Key antioxidants include

vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription di ...

and

vitamin E Vitamin E is a group of eight compounds related in molecular structure that includes four tocopherols and four tocotrienols. The tocopherols function as fat-soluble antioxidants which may help protect cell membranes from reactive oxygen speci ...

. Additionally,

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

including

superoxide dismutase Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () anion radical into normal molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxy ...

catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting ...

, and

peroxidase Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides, and should not be confused with other ...

contribute to the

oxidation response Oxidation response is stimulated by a disturbance in the balance between the production of reactive oxygen species and antioxidant responses, known as oxidative stress. Active species of oxygen naturally occur in aerobic cells and have both intracel ...

by reducing the presence of

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...

, which is a prevalent precursor of the hydroxyl radical ({{chem2, OH•). As an example, vitamin E can donate a hydrogen atom to the lipid hydroperoxyl radical ({{Chem2, LOO•) to form a vitamin E radical, which further reacts with another lipid hydroperoxyl radical ({{Chem2, LOO•) forming non-radical products.

Medical implications

Phototherapy Light therapy, also called phototherapy or bright light therapy is the exposure to direct sunlight or artificial light at controlled wavelengths in order to treat a variety of medical disorders, including seasonal affective disorder (SAD), circ ...

may cause lipid peroxidation, leading to the rupture of

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

cell membranes. End-products of lipid peroxidation may be

mutagenic In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...

and

carcinogenic A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and Biological agent, biologic agent ...

. For instance, the end-product MDA reacts with

deoxyadenosine Deoxyadenosine (symbol dA or dAdo) is a deoxyribonucleoside. It is a derivative of the nucleoside adenosine, differing from the latter by the replacement of a hydroxyl group (-OH) by hydrogen (-H) at the 2′ position of its ribose sugar moiety ...

and

deoxyguanosine Deoxyguanosine is composed of the purine nucleobase guanine linked by its N9 nitrogen to the C1 carbon of deoxyribose. It is similar to guanosine, but with one hydroxyl group removed from the 2' position of the ribose sugar (making it deoxyribose ...

in DNA, forming

DNA adducts In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could lead to the development of cancerous cells, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers of exposure ...

to them, primarily M₁G. Reactive aldehydes can also form Michael adducts or

Schiff base In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldim ...

s with

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

groups in amino acid side chains. Thus, they are able to inactivate sensitive proteins through electrophilic stress. The toxicity of lipid hydroperoxides to animals is best illustrated by the lethal phenotype of glutathione peroxidase 4 (

GPX4 Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the ''GPX4'' gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation. Discovery GPX4 was first discovered in ...

) knockout mice. These animals do not survive past embryonic day 8, indicating that the removal of lipid hydroperoxides is essential for mammalian life.{{cite journal , author = Muller, F. L., Lustgarten, M. S., Jang, Y., Richardson, A. and Van Remmen, H. , date = 2007 , title = Trends in oxidative aging theories , journal = Free Radical Biology and Medicine, volume = 43 , issue = 4 , pages = 477–503, pmid = 17640558 , doi = 10.1016/j.freeradbiomed.2007.03.034 It is unclear whether dietary lipid peroxides are bioavailable and play a role in disease, as a healthy human body has protective mechanisms in place against such hazards.{{Cite journal, url = https://link.springer.com/article/10.1007/s11746-017-2958-2, doi = 10.1007/s11746-017-2958-2, title = Biological Implications of Lipid Oxidation Products, year = 2017, last1 = Vieira, first1 = Samantha A., last2 = Zhang, first2 = Guodong, last3 = Decker, first3 = Eric A., journal = Journal of the American Oil Chemists' Society, volume = 94, issue = 3, pages = 339–351, s2cid = 90319530, access-date = 2021-04-13, archive-date = 2021-04-13, archive-url = https://web.archive.org/web/20210413013733/https://link.springer.com/article/10.1007/s11746-017-2958-2, url-status = live, url-access = subscription

Tests

Certain diagnostic tests are available for the quantification of the end-products of lipid peroxidation, to be specific,

malondialdehyde Malondialdehyde belong to the class of β-dicarbonyls. A colorless solid, malondialdehyde is a highly reactive compound that occurs as the enol. It is a physiological metabolite, and a marker for oxidative stress. Structure and synthesis Malon ...

(MDA).{{cite journal , pmid = 10064852 , journal = Mutation Research , volume = 424 , issue = 1–2, pages = 83–95 , title = Lipid peroxidation-DNA damage by malondialdehyde , date = March 1999 , last1 = Marnett , first1 = LJ , doi = 10.1016/s0027-5107(99)00010-x The most commonly used test is called a

TBARS Thiobarbituric acid reactive substances (TBARS) are formed as a byproduct of lipid peroxidation (i.e. as degradation products of fats) which can be detected by the TBARS assay using thiobarbituric acid as a reagent. TBARS can be upregulated, for ...

Assay (

thiobarbituric acid Thiobarbituric acid is an organic compound and a heterocycle. It is used as a reagent in assaying malondialdehyde (the TBARS assay of lipid peroxidation Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidat ...

reactive substances assay). Thiobarbituric acid reacts with malondialdehyde to yield a fluorescent product. However, there are other sources of malondialdehyde, so this test is not completely specific for lipid peroxidation.{{cite journal , doi = 10.1093/aje/154.4.348, pmid = 11495858, title = Correlates of Markers of Oxidative Status in the General Population, journal = American Journal of Epidemiology, volume = 154, issue = 4, pages = 348–56, year = 2001, last1 = Trevisan, first1 = M., last2 = Browne, first2 = R, last3 = Ram, first3 = M, last4 = Muti, first4 = P, last5 = Freudenheim, first5 = J, last6 = Carosella, first6 = A. M., last7 = Armstrong, first7 = D, doi-access = free

References

{{reflist

External links

* {{MeshName, Lipid+peroxidation {{DEFAULTSORT:Lipid Peroxidation Biochemical reactions Lipid metabolism Organic oxidation reactions Organic redox reactions