Malondialdehyde (T3D4182)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (5)XML
Targets (5)
Record Information
Version2.0
Creation Date2014-08-29 05:50:41 UTC
Update Date2014-12-24 20:26:41 UTC
Accession NumberT3D4182
Identification
Common NameMalondialdehyde
ClassSmall Molecule
DescriptionMalondialdehyde is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Malondialdehyde (MDA) is the dialdehyde of malonic acid and a biomarker of oxidative damage to lipids caused by smoking. Oxidized lipids are able to produce MDA as a decomposition product. The mechanism is thought to involve formation of prostaglandin-like endoperoxides from polyunsaturated fatty acids with two or more double bonds. An alternative mechanism is based on successive hydroperoxide formation and _-cleavage of polyunsaturated fatty acids. MDA is then directly formed by _-scission of a 3-hydroperoxyaldehyde or by reaction between acrolein and hydroxyl radicals. While oxidation of polyunsaturated fatty acids is the major source of MDA in vivo, other minor sources exists such as byproducts of free radical generation by ionizing radiation and of the biosynthesis of prostaglandins. Aldehydes are generally reactive species capable of forming adducts and complexes in biological systems and MDA is no exception although the main species at physiological pH is the enolate ion which is of relative low reactivity. Consistent evidence is available for the reaction between MDA and cellular macromolecules such as proteins, RNA and DNA. MDA reacts with DNA to form adducts to deoxyguanosine and deoxyadenosine which may be mutagenic and these can be quantified in several human tissues. Oxidative stress is an imbalance between oxidants and antioxidants on a cellular or individual level. Oxidative damage is one result of such an imbalance and includes oxidative modification of cellular macromolecules, induction of cell death by apoptosis or necrosis, as well as structural tissue damage. Chemically speaking, oxidants are compounds capable of oxidizing target molecules. This can take place in three ways: abstraction of hydrogen, abstraction of electrons or addition of oxygen. All cells living under aerobic conditions are continuously exposed to a large numbers of oxidants derived from various endogenous and exogenous sources. The endogenous sources of oxidants are several and include the respiratory chain in the mitochondria, immune reactions, enzymes such as xanthine oxidase and nitric oxide synthase and transition metal mediated oxidation. Various exogenous sources of ROS also contribute directly or indirectly to the total oxidant load. These include effects of ionizing and non-ionizing radiation, air pollution and natural toxic gases such as ozone, and chemicals and toxins including oxidizing disinfectants. A poor diet containing inadequate amounts of nutrients may also indirectly result in oxidative stress by impairing cellular defense mechanisms. The cellular macromolecules, in particular lipids, proteins and DNA, are natural targets of oxidation. Oxidants are capable of initiating lipid oxidation by abstraction of an allylic proton from a polyunsaturated fatty acid. This process, by multiple stages leading to the formation of lipid hydroperoxides, is a known contributor to the development of atherosclerosis. (1).
Compound Type
  • Disinfectant
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Pollutant
  • Uremic Toxin
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1,3-Propanedial
1,3-Propanedialdehyde
1,3-Propanedione
Malonaldehyde
Malonic aldehyde
Malonic dialdehyde
Malonodialdehyde
Malonyldialdehyde
MDD
Propanedial
Chemical FormulaC3H4O2
Average Molecular Mass72.063 g/mol
Monoisotopic Mass72.021 g/mol
CAS Registry Number542-78-9
IUPAC Namepropanedial
Traditional Namemalonaldehyde
SMILESO=CCC=O
InChI IdentifierInChI=1S/C3H4O2/c4-2-1-3-5/h2-3H,1H2
InChI KeyInChIKey=WSMYVTOQOOLQHP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1,3-dicarbonyl compounds. These are carbonyl compounds with the generic formula O=C(R)C(H)C(R')=O, where R and R' can be any group.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct Parent1,3-dicarbonyl compounds
Alternative Parents
Substituents
  • 1,3-dicarbonyl compound
  • Alpha-hydrogen aldehyde
  • Organic oxide
  • Hydrocarbon derivative
  • Short-chain aldehyde
  • Aldehyde
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point72°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility241 g/LALOGPS
logP0.1ALOGPS
logP-0.65ChemAxon
logS0.52ALOGPS
pKa (Strongest Acidic)6.68ChemAxon
pKa (Strongest Basic)-6.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity17.14 m³·mol⁻¹ChemAxon
Polarizability6.42 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006x-9000000000-f27c7e0c26f7fd9a353b2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-9000000000-744a9fd4b0afe1939db82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05fr-9000000000-38c741cd3f463e2fdbb32016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-18018045cdfb4fd65e5b2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-9000000000-bd4fb7676d96faa150282016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-9000000000-45f19081a5a0a9b818522016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ukc-9000000000-01e3136b16e8f53d525c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-9000000000-3d8581e7b0d371dd29232021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052f-9000000000-2a7f481a2402d9628b462021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-5846b4edd05c82b946ec2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-9000000000-85ee1d7f8db31720e3cf2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9000000000-c9a8aeda6f81e0b439e22021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-6269ba171aca8de72e5f2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as malondialdehyde are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (3). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (4).
MetabolismUremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (5)
Uses/SourcesNaturally produced by the body (endogenous).
Minimum Risk LevelNot Available
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
SymptomsAs a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB03057
HMDB IDHMDB06112
PubChem Compound ID10964
ChEMBL IDCHEMBL446036
ChemSpider ID10499
KEGG IDC19440
UniProt IDNot Available
OMIM ID
ChEBI ID566274
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDMDD
ACToR IDNot Available
Wikipedia LinkMalondialdehyde
References
Synthesis Reference

Dietrich Mangold, Josef Wahl, Wolf-Karlo Aders, “Preparation of acetals of malonaldehyde.” U.S. Patent US4410733, issued November, 1976.

MSDST3D4182.pdf
General References
  1. Lykkesfeldt J: Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin Chim Acta. 2007 May 1;380(1-2):50-8. Epub 2007 Feb 7. [17336279 ]
  2. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24. [22626821 ]
  3. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  4. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
  5. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Aldehyde dehydrogenase family 3 member B1
General Function:
Aldehyde dehydrogenase [nad(p)+] activity
Specific Function:
Oxidizes medium and long chain saturated and unsaturated aldehydes. Metabolizes also benzaldehyde. Low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. May not metabolize short chain aldehydes. May use both NADP(+) and NAD(+) as cofactors. May have a protective role against the cytotoxicity induced by lipid peroxidation.
Gene Name:
ALDH3B1
Uniprot ID:
P43353
Molecular Weight:
51839.245 Da
References
  1. Marchitti SA, Brocker C, Orlicky DJ, Vasiliou V: Molecular characterization, expression analysis, and role of ALDH3B1 in the cellular protection against oxidative stress. Free Radic Biol Med. 2010 Nov 15;49(9):1432-43. doi: 10.1016/j.freeradbiomed.2010.08.004. Epub 2010 Aug 10. [20699116 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details
2. Klotho
General Function:
Vitamin d binding
Specific Function:
May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Gene Name:
KL
Uniprot ID:
Q9UEF7
Molecular Weight:
116179.815 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details
3. NADPH oxidase 4
General Function:
Superoxide-generating nadph oxidase activity
Specific Function:
Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
Gene Name:
NOX4
Uniprot ID:
Q9NPH5
Molecular Weight:
66930.995 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details
4. Solute carrier family 22 member 8
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
5. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da