malondialdehyde
{{Use dmy dates|date=September 2023}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 435630162
| Name = Malondialdehyde
| ImageFile = Malondialdehyd.svg
| ImageFileL1 = Malondialdehyde Enol-Form.png
| ImageSizeL1 = 150
| ImageFileR1 = Malondialdehyde Keto-Form.png
| ImageSizeR1 = 150
| IUPACName = propanedial
| OtherNames = Malonic aldehyde; Malonodialdehyde; Propanedial; 1,3-Propanedial ; Malonaldehyde ; Malonyldialdehyde
|Section1={{Chembox Identifiers
| Abbreviations = MDA
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 542-78-9
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4Y8F71G49Q
| PubChem = 10964
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C19440
| SMILES = O=CCC=O
| SMILES_Comment = dialdehyde
| SMILES1 = OC=CC=O
| SMILES1_Comment = enol
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 10499
| InChI = 1/C3H4O2/c4-2-1-3-5/h2-3H,1H2
| InChIKey = WSMYVTOQOOLQHP-UHFFFAOYAU
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C3H4O2/c4-2-1-3-5/h2-3H,1H2
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = WSMYVTOQOOLQHP-UHFFFAOYSA-N
}}
|Section2={{Chembox Properties
| C=3 | H=4 | O=2
| MeltingPtC = 72
| Density = 0.991 g/mL
| BoilingPtC = 108
| Appearance = Needle-like solid{{PGCH|0377}}
}}
|Section3={{Chembox Hazards
}}
|Section4={{Chembox Related
| OtherFunction_label = alkenals
| OtherFunction = Glucic acid
}}
}}
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:V. Nair, C. L. O'Neil, P. G. Wang "Malondialdehyde", Encyclopedia of Reagents for Organic Synthesis, 2008, John Wiley & Sons, New York. {{doi|10.1002/047084289X.rm013.pub2}} 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, 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.{{cite journal | author=Davey MW1, Stals E, Panis B, Keulemans J, Swennen RL | title=High-Throughput Determination of Malondialdehyde in Plant Tissues | journal=Analytical Biochemistry | volume=347 | issue=2 | year=2005 | pages=201–207 | doi=10.1016/j.ab.2005.09.041 | pmid=16289006}} 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).{{cite journal |doi=10.1021/cr000068x |title=Mechanism of Free Radical Oxygenation of Polyunsaturated Fatty Acids by Cyclooxygenases |date=2003 |last1=Rouzer |first1=Carol A. |last2=Marnett |first2=Lawrence J. |journal=Chemical Reviews |volume=103 |issue=6 |pages=2239–2304 |pmid=12797830 }} The degree of lipid peroxidation can be estimated by the amount of malondialdehyde in tissues.
Reactive oxygen species degrade polyunsaturated lipids, forming malondialdehyde.{{cite journal |vauthors=Pryor WA, Stanley JP |title=Letter: A suggested mechanism for the production of malondialdehyde during the autoxidation of polyunsaturated fatty acids. Nonenzymatic production of prostaglandin endoperoxides during autoxidation |journal=J. Org. Chem. |volume=40 |issue=24 |pages=3615–7 |year=1975 |pmid=1185332 |doi=10.1021/jo00912a038}} 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).{{cite journal |vauthors=Farmer EE, Davoine C |title=Reactive electrophile species |journal=Curr. Opin. Plant Biol. |volume=10 |issue=4 |pages=380–6 |year=2007 |pmid=17646124 |doi=10.1016/j.pbi.2007.04.019|bibcode=2007COPB...10..380F }} The production of this aldehyde is used as a biomarker to measure the level of oxidative stress in an organism.{{cite journal |vauthors=Moore K, Roberts LJ |title=Measurement of lipid peroxidation |journal=Free Radic. Res. |volume=28 |issue=6 |pages=659–71 |year=1998 |pmid=9736317 |doi=10.3109/10715769809065821}}{{cite journal |vauthors=Del Rio D, Stewart AJ, Pellegrini N |title=A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress |journal=Nutr Metab Cardiovasc Dis |volume=15 |issue=4 |pages=316–28 |year=2005 |pmid=16054557 |doi=10.1016/j.numecd.2005.05.003}}
Malondialdehyde reacts with deoxyadenosine and deoxyguanosine in DNA, forming DNA adducts, the primary one being M1G, which is mutagenic.{{cite journal |author=Marnett LJ |title=Lipid peroxidation-DNA damage by malondialdehyde |journal=Mutat. Res. |volume=424 |issue=1–2 |pages=83–95 |year=1999 |pmid=10064852 |doi=10.1016/S0027-5107(99)00010-X|bibcode=1999MRFMM.424...83M }} 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.{{cite web |url=http://www.amdcc.org/shared/showFile.aspx?doctypeid=3&docid=33 |title=Thiobarbituric acid reactive substances (TBARS) Assay |website=www.amdcc.org |archive-url=https://web.archive.org/web/20060914082200/http://www.amdcc.org/shared/showFile.aspx?doctypeid=3&docid=33 |archive-date=September 14, 2006}} 1-Methyl-2-phenylindole is an alternative more selective reagent.
Hazards and pathology
Malondialdehyde is reactive and potentially mutagenic.Hartman PE, Putative mutagens and carcinogens in foods. IV. Malonaldehyde (malondialdehyde) Environ Mutagen. 1983;5(4):603-7 It has been found in heated edible oils such as sunflower and palm oils.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. {{doi|10.1111/j.1745-4514.2008.00195.x}}
Corneas of patients with keratoconus and bullous keratopathy have increased levels of malondialdehyde, according to one study.{{cite journal |vauthors=Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ |title=Evidence of oxidative stress in human corneal diseases |journal=J. Histochem. Cytochem. |volume=50 |issue=3 |pages=341–51 |date=March 2002 |pmid=11850437 |doi=10.1177/002215540205000306 |doi-access=free }} MDA also can be found in tissue sections of joints from patients with osteoarthritis.{{cite journal |vauthors=Tiku ML, Narla H, Jain M, Yalamanchili P |title=Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation |journal=Arthritis Research & Therapy |volume=9 |issue=4 |pages=R76 |year=2007 |pmid=17686167 |pmc=2206377 |doi=10.1186/ar2274 |doi-access=free }}
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.{{Cite journal|last1=Collodel|first1=G.|last2=Moretti|first2=E.|last3=Micheli|first3=L.|last4=Menchiari|first4=A.|last5=Moltoni|first5=L.|last6=Cerretani|first6=D.|date=March 2015|title=Semen characteristics and malondialdehyde levels in men with different reproductive problems|journal=Andrology|language=en|volume=3|issue=2|pages=280–286|doi=10.1111/andr.297|pmid=25331426|s2cid=28027300|doi-access=free}}