3,4-Dihydroxyphenylacetaldehyde

3,4-Dihydroxyphenylacetaldehyde
Names

Preferred IUPAC name (3,4-Dihydroxyphenyl)acetaldehyde
Other names DOPAL; 2-(3,4-Dihydroxyphenyl)acetaldehyde; Dopaldehyde; Dopamine aldehyde
Identifiers
CAS Number	5707-55-1
3D model (JSmol)	Interactive image Interactive image
3DMet	B00668
Abbreviations	DOPAL
ChEBI	CHEBI:27978
ChemSpider	106504
ECHA InfoCard	100.237.172
IUPHAR/BPS	6632
KEGG	C04043
MeSH	3,4-dihydroxyphenylacetaldehyde
PubChem CID	119219
UNII	F2E9Q24TSL
CompTox Dashboard (EPA)	DTXSID10205680
InChI InChI=1S/C8H8O3/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,4-5,10-11H,3H2Key: IADQVXRMSNIUEL-UHFFFAOYSA-N InChI=1/C8H8O3/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,4-5,10-11H,3H2Key: IADQVXRMSNIUEL-UHFFFAOYAV
SMILES Oc1ccc(CC=O)cc1O OC1=CC=C(CC=O)C=C1O
Properties
Chemical formula	C₈H₈O₃
Molar mass	152.149 g·mol
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 , 100 kPa). N verify (what is ?) Infobox references

Chemical compound

3,4-Dihydroxyphenylacetaldehyde (DOPAL), also known as dopamine aldehyde, is a metabolite of the monoamine neurotransmitter dopamine formed by monoamine oxidase (MAO).

Other metabolic pathways of dopamine metabolism include methylation by catechol O-methyltransferase (COMT) into 3-methoxytyramine and β-hydroxylation by dopamine β-hydroxylase (DBH) into norepinephrine. There is also spontaneous oxidation of dopamine into dopamine quinones and reactive oxygen species.

Dopaminergic neurotoxicity

DOPAL is known to be a dopaminergic neurotoxin. It is much more potent in this regard than dopamine itself and other metabolites of dopamine. According to the catecholaldehyde hypothesis, DOPAL plays a role in aging-related dopaminergic neurodegeneration and in the pathogenesis of Parkinson's disease. DOPAL is detoxified mainly by aldehyde dehydrogenase (ALDH). DOPAL is a metabolite of dopamine formed by monoamine oxidase (MAO). In differentiated neuronal cells of the 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.

Aldehyde dehydrogenase inhibitors (ALDH inhibitors), which prevent the catabolism of DOPAL and thereby increase DOPAL levels, can produce dopaminergic neurotoxicity or augment dopaminergic neurodegeneration. Examples of ALDH inhibitors include disulfiram and other known dopaminergic neurotoxins including benomyl, daidzin, dieldrin, methylmercury, rotenone, and ziram. DOPAL itself is also known to inhibit ALDH at high concentrations (>5 μM).

References

"3,4-dihydroxyphenylacetaldehyde - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 24 June 2005. Identification and Related Records. Retrieved 13 October 2011.
^ 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.
^ 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.
^ 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.
^ 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.

Neurotransmitter metabolic intermediates

Catecholamines

Anabolism

Phenylalanine → Tyrosine → DOPA (levodopa) → Dopamine → Norepinephrine → Epinephrine

Catabolism

Dopamine	3,4-Dihydroxyphenylacetaldehyde (DOPAL) 3,4-Dihydroxyphenylacetic acid (DOPAC) Homovanillyl alcohol Hydroxytyrosol (3,4-dihydroxyphenylethanol; DOPET) 3-Methoxytyramine (3-MT) Homovanillic acid (HVA)
Norepinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) 3,4-Dihydroxymandelic acid (DHMA) Normetanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL) Vanillylmandelic acid (VMA) 3,4-Dihydroxyphenylethylene glycol (DOPEG, DHPG) 3-Methoxy-4-hydroxyphenylglycol (MHPG, MOPEG)
Epinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) Metanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL)

Tryptophan→Serotonin

Anabolism	Tryptophan 5-Hydroxytryptophan (5-HTP)
Catabolism	5-Hydroxyindoleacetaldehyde (5-HIAL) 5-Hydroxyindoleacetic acid (5-HIAA) 5-Hydroxytryptophol (5-HTOL)

Serotonin→Melatonin

Trace amines

GABA

v t e Monoaminergic neurotoxins
Dopaminergic	2′-CH₃-MPTP (2′-methyl-MPTP) 2,4,5-THA 2,4,5-THMA 5-S-Cysteinyldopamine 5,6-DHT 6-Hydroxydopa 6-OHDA quinone 6,7-DHT ALDH inhibitors (e.g., disulfiram, methylmercury) Amphetamine Benomyl Daidzin Dieldrin DOPA quinone DOPAL DOPAL quinone Dopamine Dopamine quinone Fenpropathrin Haloperidol HPP HPTP Mancozeb Maneb Mephedrone Methamphetamine Methylone MPP (cyperquat) MPTP N-Methylnorsalsolinol Norsalsolinol Oxidopamine (6-OHDA) Paraquat Rotenone Salsolinol Ziram
Noradrenergic	2′-NH₂-MPTP (2′-amino-MPTP) 2,4,5-THA 4,5-DHT 5,6-DHT 5,7-DHT 6-Hydroxydopa DOPEGAL DSP-4 MDA (tenamfetamine) Oxidopamine (6-OHDA) Xylamine
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 4,5-DHT 5-IAI 5-MAPB 5,6-DHT 5,7-DHT 6,7-DHT αET Fenfluramine Haloperidol HHA (α-methyldopamine) HHMA (α-methylepinine, α,N-dimethyldopamine) HPP HPTP MBDB MDA (tenamfetamine) MDMA (midomafetamine) Mephedrone Methamphetamine Methylone Norfenfluramine PBA PCA PIA
Unsorted	5-HIAL RHPP RHPTP
See also: Receptor/signaling modulators • Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake inhibitors • Monoamine releasing agents • Monoamine metabolism modulators

Categories:

Dopaminergic neurotoxicity

See also

References