Malondialdehyde (MDA) is the

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the nominal

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...

CH₂(CHO)₂. A colorless liquid, malondialdehyde is a highly reactive compound that occurs as the

enol In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The te ...

. It occurs naturally and is a marker for

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

Structure and synthesis

Malondialdehyde mainly exists as the

:V. Nair, C. L. O'Neil, P. G. Wang "Malondialdehyde", ''Encyclopedia of Reagents for Organic Synthesis'', 2008, John Wiley & Sons, New York. Article Online Posting Date: March 14, 2008 :CH₂(CHO)₂ → HOC(H)=CH-CHO In organic solvents, the ''cis''-isomer is favored, whereas in water the ''trans''-isomer predominates. The equilibrium is rapid and is inconsequential for many purposes. In the laboratory it can be generated in situ by hydrolysis of its acetal

1,1,3,3-tetramethoxypropane 1,1,3,3-Tetramethoxypropane is an organic compound with the formula CH(CH(OCH)). A colorless liquid, it is a protected form of malondialdehyde Malondialdehyde (MDA) is the organic compound with the nominal formula CH2(CHO)2. A colorless liquid, ...

, which is commercially available and shelf-stable, unlike malondialdehyde. Malondialdehyde is easily deprotonated to give the sodium salt of the enolate (m.p. 245 °C).

Biosynthesis and reactivity

Malondialdehyde results from lipid peroxidation of

polyunsaturated fatty acids 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 ...

. It is a prominent product in

thromboxane A2 Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets during hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by act ...

synthesis wherein

cyclooxygenase 1 Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prosta ...

or cycloxygenase 2 metabolizes

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 structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...

prostaglandin H2 Prostaglandin H2 is a type of prostaglandin and a precursor for many other biologically significant molecules. It is synthesized from arachidonic acid in a reaction catalyzed by a cyclooxygenase enzyme. The conversion from Arachidonic acid to P ...

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

and a wide array of other cell types and tissues. This product is further metabolized by

thromboxane synthase Thromboxane A synthase 1 (, platelet, cytochrome P450, family 5, subfamily A), also known as TBXAS1, is a cytochrome P450 enzyme that, in humans, is encoded by the ''TBXAS1'' gene. Function This gene encodes a member of the cytochrome P450 supe ...

, 12-hydroxyheptadecatrienoic acid, and malonyldialdehyde. Alternatively, it may rearrange non-enzymatically to a mixture of 8-cis and 8-trans isomers of 12-hydroxyeicosaheptaenoic acid plus malonyldialdehyde (see 12-Hydroxyheptadecatrienoic acid). The degree of lipid peroxidation can be estimated by the amount of malondialdehyde in tissues.

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 ...

degrade polyunsaturated lipids, forming malondialdehyde. This compound is a reactive

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

and is one of the many reactive electrophile species that cause toxic stress in cells and form covalent protein adducts referred to as advanced lipoxidation end-products (ALE), in analogy to

advanced glycation end-products Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, ath ...

(AGE). The production of this aldehyde is used as a biomarker to measure the level of

in an organism. Malondialdehyde 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, the primary one being M₁G, which is

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 i ...

. The guanidine group of arginine residues condense with malondialdehyde to give 2-aminopyrimidines. Human ALDH1A1 aldehyde dehydrogenase is capable of oxidizing malondialdehyde.

Analysis

Malondialdehyde and other thiobarbituric reactive substances (TBARS) condense with two equivalents of

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 ...

to give a fluorescent red derivative that can be assayed spectrophotometrically. 1-Methyl-2-phenylindole is an alternative more selective reagent.

Hazards and pathology

Malondialdehyde is reactive and potentially mutagenic. It has been found in heated edible oils such as sunflower and palm oils.

Cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

s of patients with

keratoconus Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usu ...

and bullous keratopathy have increased levels of malondialdehyde, according to one study. MDA also can be found in tissue sections of joints from patients with

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

. Levels of malondialdehyde can be also considered (as a marker of lipid peroxidation) to assess the membrane damage in spermatozoa; this is crucial because

affects sperm function by altering membrane fluidity, permeability and impairing sperm functional competence.

References

{{reflist Aldehydes 3-Hydroxypropenals

Structure and synthesis

Biosynthesis and reactivity

Analysis

Hazards and pathology

See also

References