Malondialdehyde belong to the class of β-dicarbonyls. A colorless liquid, malondialdehyde is a highly reactive compound that occurs as the enol. It is a physiological metabolite, and a marker for oxidative stress.
Malondialdehyde mainly exists as its enol, hydroxyacrolein:[1]
CH2(CHO)2 → HOC(H)=CH-CHOIn 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, which is commercially available and shelf-stable, unlike malondialdehyde.[1] Malondialdehyde is easily deprotonated to give the sodium salt of the enolate (m.p. 245 °C).
Malondialdehyde results from lipid peroxidation of polyunsaturated fatty acids.[2] It is a prominent product in thromboxane A2 synthesis wherein cyclooxygenase 1 or cycloxygenase 2 metabolizes arachidonic acid to prostaglandin H2 by platelets and a wide array of other cell types and tissues. This product is further metabolized by thromboxane synthase to thromboxane A2, 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).[3] The degree of lipid peroxidation can be estimated by the amount of malondialdehyde in tissues.
Reactive oxygen species degrade polyunsaturated lipids, forming malondialdehyde.[4] This compound is a reactive aldehyde 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 (AGE).[5] The production of this aldehyde is used as a biomarker to measure the level of oxidative stress in an organism.[6] [7]
Malondialdehyde reacts with deoxyadenosine and deoxyguanosine in DNA, forming DNA adducts, the primary one being M1G, which is mutagenic.[8] The guanidine group of arginine residues condense with malondialdehyde to give 2-aminopyrimidines.
Human ALDH1A1 aldehyde dehydrogenase is capable of oxidizing malondialdehyde.
Malondialdehyde and other thiobarbituric reactive substances (TBARS) condense with two equivalents of thiobarbituric acid to give a fluorescent red derivative that can be assayed spectrophotometrically.[1] [9] 1-Methyl-2-phenylindole is an alternative more selective reagent.[1]
Malondialdehyde is reactive and potentially mutagenic.[10] It has been found in heated edible oils such as sunflower and palm oils.[11]
Corneas of patients with keratoconus and bullous keratopathy have increased levels of malondialdehyde, according to one study.[12] MDA also can be found in tissue sections of joints from patients with osteoarthritis.[13]
Levels of malondialdehyde can be also considered (as a marker of lipid peroxidation) to assess the membrane damage in spermatozoa; this is crucial because oxidative stress affects sperm function by altering membrane fluidity, permeability and impairing sperm functional competence.[14]