3,4-Dihydroxyphenylacetaldehyde Explained

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.[1] [2] [3] 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.[4] 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.[5]

Aldehyde dehydrogenase inhibitors (ALDH inhibitors), which prevent the catabolism of DOPAL and thereby increase DOPAL levels, can produce dopaminergic neurotoxicity or augment dopaminergic neurodegeneration.[6] [7] [8] 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 (>5μM).

See also

Notes and References

  1. Goldstein DS . The catecholaldehyde hypothesis: where MAO fits in . J Neural Transm (Vienna) . 127 . 2 . 169–177 . February 2020 . 31807952 . 10680281 . 10.1007/s00702-019-02106-9 .
  2. Goldstein DS . The "Sick-but-not-Dead" Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases . Semin Neurol . 40 . 5 . 502–514 . October 2020 . 32906170 . 10680399 . 10.1055/s-0040-1713874 .
  3. Goldstein DS . The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know . Int J Mol Sci . 22 . 11 . June 2021 . 5999 . 34206133 . 8199574 . 10.3390/ijms22115999 . free .
  4. 10.1111/jnc.12345 . Determinants of buildup of the toxic dopamine metabolite DOPAL in Parkinson's disease . 2013 . Goldstein . David S. . Sullivan . Patti . Holmes . Courtney . Miller . Gary W. . Alter . Shawn . Strong . Randy . Mash . Deborah C. . Kopin . Irwin J. . Sharabi . Yehonatan . Journal of Neurochemistry . 126 . 5 . 591–603 . 23786406 . 4096629 .
  5. 10.1016/s0891-5849(01)00484-1 . Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria . 2001 . Kristal . B. . Conway . A. D. . Brown . A. M. . Jain . J. C. . Ulluci . P. A. . Li . S. W. . Burke . W. J. . Free Radical Biology and Medicine . 30 . 8 . 924–931 . 11295535 .
  6. Masato A, Plotegher N, Boassa D, Bubacco L . Impaired dopamine metabolism in Parkinson's disease pathogenesis . Mol Neurodegener . 14 . 1 . 35 . August 2019 . 31488222 . 6728988 . 10.1186/s13024-019-0332-6 . free .
  7. Doorn JA, Florang VR, Schamp JH, Vanle BC . Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons . Parkinsonism Relat Disord . 20 Suppl 1 . 1 . S73–S75 . January 2014 . 24262193 . 3932615 . 10.1016/S1353-8020(13)70019-1 .
  8. Legros H, Dingeval MG, Janin F, Costentin J, Bonnet JJ . 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 . March 2004 . 15019299 . 10.1016/S0161-813X(03)00148-7 . 2004NeuTx..25..365L .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "3,4-Dihydroxyphenylacetaldehyde".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2025, A B Cryer, All Rights Reserved. Cookie policy.