Basic Info

Common NameMalondialdehyde(F05266)
2D Structure
Description

Malondialdehyde 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. (A3296).

FRCD IDF05266
CAS Number542-78-9
PubChem CID10964
FormulaC3H4O2
IUPAC Name

propanedial

InChI Key

WSMYVTOQOOLQHP-UHFFFAOYSA-N

InChI

InChI=1S/C3H4O2/c4-2-1-3-5/h2-3H,1H2

Canonical SMILES

C(C=O)C=O

Isomeric SMILES

C(C=O)C=O

WikipediaMalondialdehyde
Synonyms
        
            MALONALDEHYDE
        
            Malondialdehyde
        
            Propanedial
        
            Malonyldialdehyde
        
            Malonodialdehyde
        
            Malonic aldehyde
        
            Malonic dialdehyde
        
            1,3-Propanedial
        
            1,3-Propanedione
        
            1,3-Propanedialdehyde
        
Classifies
                

                  
                    Pollutant
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganic oxygen compounds
ClassOrganooxygen compounds
SubclassCarbonyl compounds
Intermediate Tree NodesNot available
Direct Parent1,3-dicarbonyl compounds
Alternative Parents
Molecular FrameworkAliphatic acyclic compounds
Substituents1,3-dicarbonyl compound - Alpha-hydrogen aldehyde - Organic oxide - Hydrocarbon derivative - Short-chain aldehyde - Aldehyde - Aliphatic acyclic compound
DescriptionThis compound 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.

Properties

Property NameProperty Value
Molecular Weight72.063
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count2
Complexity34.2
Monoisotopic Mass72.021
Exact Mass72.021
XLogP-0.6
Formal Charge0
Heavy Atom Count5
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9901
Human Intestinal AbsorptionHIA+0.9782
Caco-2 PermeabilityCaco2+0.6417
P-glycoprotein SubstrateNon-substrate0.8763
P-glycoprotein InhibitorNon-inhibitor0.9257
Non-inhibitor0.9667
Renal Organic Cation TransporterNon-inhibitor0.9194
Distribution
Subcellular localizationMitochondria0.7033
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8634
CYP450 2D6 SubstrateNon-substrate0.9106
CYP450 3A4 SubstrateNon-substrate0.8195
CYP450 1A2 InhibitorNon-inhibitor0.8284
CYP450 2C9 InhibitorNon-inhibitor0.9214
CYP450 2D6 InhibitorNon-inhibitor0.9408
CYP450 2C19 InhibitorNon-inhibitor0.9036
CYP450 3A4 InhibitorNon-inhibitor0.9459
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9419
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9095
Non-inhibitor0.9859
AMES ToxicityAMES toxic0.8718
CarcinogensCarcinogens 0.6596
Fish ToxicityLow FHMT0.6921
Tetrahymena Pyriformis ToxicityHigh TPT0.9172
Honey Bee ToxicityHigh HBT0.7399
BiodegradationReady biodegradable0.8375
Acute Oral ToxicityIII0.8280
Carcinogenicity (Three-class)Non-required0.6912

Model Value Unit
Absorption
Aqueous solubility0.5002LogS
Caco-2 Permeability1.1959LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.2325LD50, mol/kg
Fish Toxicity0.3121pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.1500pIGC50, ug/L

References

TitleJournalDatePubmed ID
Effects of aged ZnO NPs and soil type on Zn availability, accumulation and toxicity to pea and beet in a greenhouse experiment.Ecotoxicol Environ Saf2018 Sep 3029807295
The protective effects of DL-Selenomethionine against T-2/HT-2 toxins-induced cytotoxicity and oxidative stress in broiler hepatocytes.Toxicol In Vitro2018 Sep 2530261313
Adducts formed during protein digestion decreased the toxicity of five carbonyl compounds against Caco-2 cells.J Hazard Mater2018 Sep 2430300775
Dietary supplementation of Yucca schidigera extract enhances productive and reproductive performances, blood profile, immune function, and antioxidant status in laying Japanese quails exposed to lead in the diet.Poult Sci2018 Sep 129846703
Kolaviron attenuates diclofenac-induced nephrotoxicity in male Wistar rats.Appl Physiol Nutr Metab2018 Sep29847737
Protective effects of compound ammonium glycyrrhizin, L‑arginine, silymarin and glucurolactone against liver damage induced by ochratoxin A in primary chicken hepatocytes.Mol Med Rep2018 Sep30015927
Fumonisin B<sub>1</sub> exposure increases Hsp70 expression in the lung and kidney of rats without inducing significant oxidative stress.Acta Vet Hung2018 Sep30264617
Protective Effect of N-Acetylcysteine against Oxidative Stress Induced by Zearalenone via Mitochondrial Apoptosis Pathway in SIEC02 Cells.Toxins (Basel)2018 Oct 930304829
Dose-related impacts of imidacloprid oral intoxication on brain and liver of rock pigeon (Columba livia domestica), residues analysis in different organs.Ecotoxicol Environ Saf2018 Oct 530296697
l-arginine protects against oxidative damage induced by T-2 toxin in mouse Leydig cells.J Biochem Mol Toxicol2018 Oct30091165
Biochemical and histological alterations in adult zebrafish(Danio rerio)ovary following exposure to the tetronic acid insecticide spirotetramat.Ecotoxicol Environ Saf2018 Nov 3030107324
Influence of sex on biomarkers of oxidative stress in the kidney, lungs, and liver of rabbits after exposure to diazinon.Environ Sci Pollut Res Int2018 Nov30232776
Selective effects of fenitrothion on murine splenic T-lymphocyte populations and cytokine/granzyme production.J Environ Sci Health B2018 May 429431569
Effect of CuSO4 and nano copper on serum antioxidant capacity in Weaned piglets.J Biol Regul Homeost Agents2018 Mar-Apr29684999
SlMYC2 Involved in Methyl Jasmonate-Induced Tomato Fruit Chilling Tolerance.J Agric Food Chem2018 Mar 2829528226
Chronic exposure to high fat diet exacerbates arsenic-induced lung damages inmale mice: Possible role for oxidative stress.Monaldi Arch Chest Dis2018 Mar 2329741077
d-Fagomine Attenuates High Glucose-Induced Endothelial Cell Oxidative Damage byUpregulating the Expression of PGC-1α.J Agric Food Chem2018 Mar 2129489344
Long-Term Excessive Selenium Supplementation Induces Hypertension in Rats.Biol Trace Elem Res2018 Mar28634813
Hepatoprotective and free radical scavenging actions of quercetin nanoparticles on aflatoxin B1-induced liver damage: in vitro/in vivo studies.Artif Cells Nanomed Biotechnol2018 Mar28423950
Methionine hydroxy analogue supplementation modulates gill immunological andbarrier health status of grass carp (Ctenopharyngodon idella).Fish Shellfish Immunol2018 Mar29360541

Targets

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. 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 ]
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 ]
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 ]
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 ]