Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

David G Anderson; S. V. Santhana Mariappan; Garry R Buettner; Jonathan A Doorn

doi:10.1074/jbc.M111.249532

Back

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Journal article

Open access

Peer reviewed

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

David G Anderson, S. V. Santhana Mariappan, Garry R Buettner and Jonathan A Doorn

The Journal of biological chemistry, Vol.286(30), pp.26978-26986

07/29/2011

DOI: 10.1074/jbc.M111.249532

PMCID: PMC3143656

PMID: 21642436

Files and links (1)

url

https://doi.org/10.1074/jbc.M111.249532View

Published (Version of record) Open Access

Abstract

The oxidation and toxicity of dopamine is believed to contribute to the selective neurodegeneration associated with Parkinson disease. The formation of reactive radicals and quinones greatly contributes to dopaminergic toxicity through a variety of mechanisms. The physiological metabolism of dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL) via monoamine oxidase significantly increases its toxicity. To more adequately explain this enhanced toxicity, we hypothesized that DOPAL is capable of forming radical and quinone species upon oxidation. Here, two unique oxidation products of DOPAL are identified. Several different oxidation methods gave rise to a transient DOPAL semiquinone radical, which was characterized by electron paramagnetic resonance spectroscopy. NMR identified the second oxidation product of DOPAL as the ortho -quinone. Also, carbonyl hydration of DOPAL in aqueous media was evident via NMR. Interestingly, the DOPAL quinone exists exclusively in the hydrated form. Furthermore, the enzymatic and chemical oxidation of DOPAL greatly enhance protein cross-linking, whereas auto-oxidation results in the production of superoxide. Also, DOPAL was shown to be susceptible to oxidation by cyclooxygenase-2 (COX-2). The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition.

Molecular Bases of Disease

Quinones

Neurotransmitters

Dopamine

Electron Paramagnetic Resonance (EPR)

3,4-Dihydroxyphenylacetaldehyde

Free Radical

Metabolism

Neurological Diseases

Details

Title: Subtitle: Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone
Creators: David G Anderson - From the
S. V. Santhana Mariappan - Central High Field NMR Research Facility, Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, and
Garry R Buettner - Free Radical and Radiation Biology Program, ESR Facility, Department of Radiation Oncology, College of Medicine, University of Iowa, Iowa City, Iowa 52242-1101
Jonathan A Doorn - From the
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.286(30), pp.26978-26986
DOI: 10.1074/jbc.M111.249532
PMID: 21642436
PMCID: PMC3143656
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: R01ES15507; R01GM073929; P42ES013661; T32GM 008365 / National Institutes of Health
Alternative title: Oxidation of DOPAL
Language: English
Date published: 07/29/2011
Academic Unit: Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Medicinal and Natural Products Chemistry
Record Identifier: 9984046926502771

Metrics

10 Record Views

90 Times Cited - Web of Science