Lipid peroxidation is the chain of reactions of

oxidative Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

degradation of

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

s. It is the process in which

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

"steal" electrons from the lipids in

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

, resulting in cell damage. This process proceeds by a free radical

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 syst ...

mechanism. It most often affects

polyunsaturated In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food. The term often refers specifically to triglycerides (triple es ...

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

, because they contain multiple double bonds in between which lie

methylene bridge In organic chemistry, a methylene bridge, methylene spacer, or methanediyl group is any part of a molecule with formula ; namely, a carbon atom bound to two hydrogen atoms and connected by single bonds to two other distinct atoms in the rest of ...

s (-CH₂-) that possess especially reactive

hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...

atoms. As with any radical reaction, the reaction consists of three major steps: initiation, propagation, and termination. The chemical products of this oxidation are known as lipid peroxides or lipid oxidation products (LOPs).

Initiation

Initiation is the step in which a fatty acid

radical Radical may refer to: Politics and ideology Politics *Radical politics, the political intent of fundamental societal change *Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...

is produced. The most notable initiators in living cells are

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(ROS), such as OH· and HOO·, which combines with a hydrogen atom to make water and a fatty acid radical.

Propagation

The fatty acid radical is not a very stable

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

, so it reacts readily with molecular oxygen, thereby creating a peroxyl-fatty acid radical. This radical is also an unstable species that reacts with another free fatty acid, producing a different fatty acid radical and a lipid peroxide, or a cyclic peroxide if it had reacted with itself. This cycle continues, as the new fatty acid radical reacts in the same way.

Termination

When a radical reacts with a non-radical, it can produce another radical, which is why the process is called a "chain reaction mechanism". The radical reaction stops when two radicals react and produce a non-radical species. This happens only when the concentration of radical species is high enough for there to be a high probability of collision of two radicals. Living organisms have different molecules that speed up termination by neutralizing free radicals and, therefore, protecting the cell membrane. Antioxidants such as vitamin C and vitamin E may inhibit lipid peroxidation. Other anti-oxidants made within the body include the enzymes

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

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 t ...

, 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. Functionality Peroxidases typically ca ...

. An alternative, pharmaceutical method employs the

isotope effect on lipid peroxidation Kinetic isotope effect, Isotope effect is observed when molecules containing heavier isotopes of the same atoms (for example, deuterium instead of hydrogen) are engaged in a chemical reaction at a slower rate. Reinforced lipids, Deuterium-reinforce ...

deuterated Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...

polyunsaturated fatty acid Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic proper ...

s (PUFAs) at the methylene bridges (bis-allylic sites) between double bonds, which leads to the inhibition of the chain reaction. Such D-PUFAs, for example, 11,11-D2-ethyl linoleate, suppress lipid peroxidation even at relatively low levels of incorporation into membranes.

Final products of lipid peroxidation

The end products of lipid peroxidation are reactive aldehydes, such as

malondialdehyde Malondialdehyde (MDA) is the organic compound with the nominal formula CH2(CHO)2. A colorless liquid, malondialdehyde is a highly reactive compound that occurs as the enol. It occurs naturally and is a marker for oxidative stress. Structure and ...

(MDA) and

4-hydroxynonenal 4-Hydroxynonenal, or 4-hydroxy-2-nonenal or 4-HNE or HNE, (), 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 ...

(HNE), the second one being known also as "second messenger of free radicals" and major bioactive marker of lipid peroxidation, due to its numerous biological activities resembling activities of reactive oxygen h species.http://informahealthcare.com/toc/fra/44/10

Hazards

If not terminated fast enough, there will be damage to the

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

, which consists mainly of lipids.

Phototherapy Light therapy, also called phototherapy or bright light therapy is intentional daily exposure to direct sunlight or similar-intensity artificial light in order to treat medical disorders, especially seasonal affective disorder (SAD) and circadi ...

may cause

hemolysis Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...

by rupturing

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

cell membranes in this way. In addition, 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 substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...

. For instance, the end-product

MDA MDA, mda, or ''variation'', may refer to: Places * Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics * Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...

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. D ...

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 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 aldimine ...

s with thiol or amine 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. Function The antioxidant enzyme glutat ...

) knockout mice. These animals do not survive past embryonic day 8, indicating that the removal of lipid hydroperoxides is essential for mammalian life. On the other hand, it's 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.

Tests

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

(MDA). 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, fo ...

Assay (

thiobarbituric acid Thiobarbituric acid is an organic compound and a heterocycle. It is used as a reagent in assaying malondialdehyde Malondialdehyde (MDA) is the organic compound with the nominal formula CH2(CHO)2. A colorless liquid, malondialdehyde is a highly r ...

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. In recent years, development of immunochemical detection of HNE-histidine adducts opened more advanced methodological possibilities for qualitative and quantitative detection of lipid peroxidation in various human and animal tissues as well as in body fluids, including human serum and plasma samples.

References

External links

* {{DEFAULTSORT:Lipid Peroxidation Lipids Organic redox reactions