3,4-Dihydroxyphenylacetaldehyde Kekulé, skeletal formula of 3,4-dihydroxyphenylacetaldehyde Names Preferred IUPAC name (3,4-Dihydroxyphenyl)acetaldehyde
Other namesDOPAL; 2-(3,4-Dihydroxyphenyl)acetaldehyde;
[ 1] Dopaldehyde; Dopamine aldehyde
Identifiers Abbreviations DOPAL ChEBI ChemSpider ECHA InfoCard 100.237.172 KEGG MeSH 3,4-dihydroxyphenylacetaldehyde UNII InChI=1S/C8H8O3/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,4-5,10-11H,3H2
Y Key: IADQVXRMSNIUEL-UHFFFAOYSA-N
Y InChI=1/C8H8O3/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,4-5,10-11H,3H2
Key: IADQVXRMSNIUEL-UHFFFAOYAV
Oc1ccc(CC=O)cc1O
OC1=CC=C(CC=O)C=C1O
Properties C 8 H 8 O 3 Molar mass −1 Density 1.306 g/mL Boiling point 351 °C (664 °F; 624 K) Related compounds Related 2-phenyl aldehydes
Phenylacetaldehyde Phenylglyoxal
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
3,4-Dihydroxyphenylacetaldehyde (DOPAL ), also known asdopamine aldehyde , is ametabolite of themonoamine neurotransmitter dopamine formed bymonoamine oxidase (MAO).[ 2] [ 3]
Othermetabolic pathways of dopaminemetabolism includemethylation bycatecholO -methyltransferase (COMT) into3-methoxytyramine andβ-hydroxylation bydopamine β-hydroxylase (DBH) intonorepinephrine . There is also spontaneousoxidation of dopamine intodopamine quinones andreactive oxygen species .[ 3]
Dopaminergic neurotoxicity [ edit ] DOPAL is known to be adopaminergic neurotoxin .[ 2] [ 4] [ 3] potent in this regard than dopamine itself and other metabolites of dopamine.[ 2] [ 4] [ 3] catecholaldehyde hypothesis , DOPAL plays a role inaging -related dopaminergicneurodegeneration and in thepathogenesis ofParkinson's disease .[ 2] [ 4] [ 3] [ 5] aldehyde dehydrogenase (ALDH).[ 2] [ 4] [ 3] monoamine oxidase (MAO).[ 2] PC12 line , physiological concentrations of DOPAL in isolated mitochondria were highly potent in inducing a pathway associated with programmed cell death (or apoptosis), permeability transition. This suggests the cytotoxity of DOPAL and its role in the progression of Parkinson's disease, which has long been associated with mitochondrial abnormalities and neurotoxicity by way of dopaminergic compounds, while reducing the emphasis on other dopamine derivatives and metabolites.[ 6]
Aldehyde dehydrogenase inhibitors (ALDH inhibitors), which prevent thecatabolism of DOPAL and thereby increase DOPAL levels, can produce dopaminergic neurotoxicity or augment dopaminergic neurodegeneration.[ 7] [ 8] [ 9] disulfiram and other knowndopaminergic neurotoxins includingbenomyl ,daidzin ,dieldrin ,methylmercury ,rotenone , andziram .[ 7] μM).[ 7]
^ "3,4-dihydroxyphenylacetaldehyde - Compound Summary" .PubChem Compound . USA: National Center for Biotechnology Information. 24 June 2005. Identification and Related Records. Retrieved13 October 2011 .^a b c d e f Goldstein DS (February 2020)."The catecholaldehyde hypothesis: where MAO fits in" .J Neural Transm (Vienna) .127 (2):169– 177.doi :10.1007/s00702-019-02106-9 .PMC 10680281 PMID 31807952 . ^a b c d e f Goldstein DS (June 2021)."The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know" .Int J Mol Sci .22 (11): 5999.doi :10.3390/ijms22115999 PMC 8199574 PMID 34206133 . ^a b c d Goldstein DS (October 2020)."The "Sick-but-not-Dead" Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases" .Semin Neurol .40 (5):502– 514.doi :10.1055/s-0040-1713874 .PMC 10680399 PMID 32906170 . ^ Goldstein, David S.; Sullivan, Patti; Holmes, Courtney; Miller, Gary W.; Alter, Shawn; Strong, Randy; Mash, Deborah C.; Kopin, Irwin J.; Sharabi, Yehonatan (2013)."Determinants of buildup of the toxic dopamine metabolite <SCP>DOPAL</SCP> in Parkinson's disease" .Journal of Neurochemistry .126 (5):591– 603.doi :10.1111/jnc.12345 .PMC 4096629 PMID 23786406 . ^ Kristal, B.; Conway, A. D.; Brown, A. M.; Jain, J. C.; Ulluci, P. A.; Li, S. W.; Burke, W. J. (2001). "Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria".Free Radical Biology and Medicine .30 (8):924– 931.doi :10.1016/s0891-5849(01)00484-1 .PMID 11295535 . ^a b c Masato A, Plotegher N, Boassa D, Bubacco L (August 2019)."Impaired dopamine metabolism in Parkinson's disease pathogenesis" .Mol Neurodegener .14 (1) 35.doi :10.1186/s13024-019-0332-6 PMC 6728988 PMID 31488222 . ^ Doorn JA, Florang VR, Schamp JH, Vanle BC (January 2014)."Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons" .Parkinsonism Relat Disord . 20 Suppl 1 (1):S73 – S75 .doi :10.1016/S1353-8020(13)70019-1 .PMC 3932615 PMID 24262193 . ^ Legros H, Dingeval MG, Janin F, Costentin J, Bonnet JJ (March 2004). "Toxicity of a treatment associating dopamine and disulfiram for catecholaminergic neuroblastoma SH-SY5Y cells: relationships with 3,4-dihydroxyphenylacetaldehyde formation".Neurotoxicology .25 (3):365– 375.Bibcode :2004NeuTx..25..365L .doi :10.1016/S0161-813X(03)00148-7 .PMID 15019299 .
Dopaminergic Noradrenergic Serotonergic 2′-NH2 -MPTP (2′-amino-MPTP) 2,4-DCA 2,4,5-THA 2,4,5-THMA 3-CA 3,4-DCA 4-CAB (α-ethyl-PCA) 4-CMA 4-HO-5-MeO-T 4,5-DHT 5-IAI 5-MAPB 5-MeO-DiPT 5,6-DHT 5,7-DHT 6,7-DHT αET ETAI Fenfluramine Haloperidol HHA (α-methyldopamine) HHMA (α-methylepinine, α,N -dimethyldopamine) HPP+ HPTP MBDB MDA (tenamfetamine) MDMA (midomafetamine) Mephedrone Methamphetamine Methylone Norfenfluramine PBA PBMA PCA PCMA PIA TAI Unsorted
