Malondialdehyde Explained

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.

Structure and synthesis

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).

Biosynthesis and reactivity

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.

Analysis

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]

Hazards and pathology

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]

See also

Notes and References

  1. 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
  2. Davey MW1, Stals E, Panis B, Keulemans J, Swennen RL . High-Throughput Determination of Malondialdehyde in Plant Tissues . . 347 . 2 . 2005 . 201–207 . 10.1016/j.ab.2005.09.041 . 16289006.
  3. 10.1021/cr000068x . Mechanism of Free Radical Oxygenation of Polyunsaturated Fatty Acids by Cyclooxygenases . 2003 . Rouzer . Carol A. . Marnett . Lawrence J. . Chemical Reviews . 103 . 6 . 2239–2304 . 12797830 .
  4. Pryor WA, Stanley JP . Letter: A suggested mechanism for the production of malondialdehyde during the autoxidation of polyunsaturated fatty acids. Nonenzymatic production of prostaglandin endoperoxides during autoxidation . J. Org. Chem. . 40 . 24 . 3615–7 . 1975 . 1185332 . 10.1021/jo00912a038.
  5. Farmer EE, Davoine C . Reactive electrophile species . Curr. Opin. Plant Biol. . 10 . 4 . 380–6 . 2007 . 17646124 . 10.1016/j.pbi.2007.04.019. 2007COPB...10..380F .
  6. Moore K, Roberts LJ . Measurement of lipid peroxidation . Free Radic. Res. . 28 . 6 . 659–71 . 1998 . 9736317 . 10.3109/10715769809065821.
  7. Del Rio D, Stewart AJ, Pellegrini N . A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress . Nutr Metab Cardiovasc Dis . 15 . 4 . 316–28 . 2005 . 16054557 . 10.1016/j.numecd.2005.05.003.
  8. Marnett LJ . Lipid peroxidation-DNA damage by malondialdehyde . Mutat. Res. . 424 . 1–2 . 83–95 . 1999 . 10064852 . 10.1016/S0027-5107(99)00010-X. 1999MRFMM.424...83M .
  9. Web site: Thiobarbituric acid reactive substances (TBARS) Assay . www.amdcc.org . https://web.archive.org/web/20060914082200/http://www.amdcc.org/shared/showFile.aspx?doctypeid=3&docid=33 . September 14, 2006.
  10. Hartman PE, Putative mutagens and carcinogens in foods. IV. Malonaldehyde (malondialdehyde) Environ Mutagen. 1983;5(4):603-7
  11. Dourerdjou, P.; Koner, B. C. (2008), Effect of Different Cooking Vessels on Heat-Induced Lipid Peroxidation of Different Edible Oils" Journal of Food Biochemistry, 32: 740–751.
  12. Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ . Evidence of oxidative stress in human corneal diseases . . 50 . 3 . 341–51 . March 2002 . 11850437 . 10.1177/002215540205000306 . free .
  13. Tiku ML, Narla H, Jain M, Yalamanchili P . Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation . . 9 . 4 . R76 . 2007 . 17686167 . 2206377 . 10.1186/ar2274 . free .
  14. Collodel. G.. Moretti. E.. Micheli. L.. Menchiari. A.. Moltoni. L.. Cerretani. D.. March 2015. Semen characteristics and malondialdehyde levels in men with different reproductive problems. Andrology. en. 3. 2. 280–286. 10.1111/andr.297. 25331426. 28027300. free.