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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00467

Dopamine Autoxidation is Controlled by Acidic pH

 Nejc Umek1, Blaz Gersak1, Neli Vintar1, Maja Sostaric1, 2 and  Janez Mavri3*
  • 1Department of Anaesthesiology and Surgical Intensive Therapy, University Medical Centre Ljubljana, Slovenia
  • 2Department of Anesthesiology and Reanimatology, Faculty of Medicine, University of Ljubljana, Slovenia
  • 3National Institute of Chemistry Slovenia, Slovenia

We studied the reaction mechanism of dopamine autoxidation using quantum chemical methods. Unlike other biogenic amines important in the central nervous system, dopamine and noradrenaline are capable of undergoing a non-enzymatic autoxidative reaction giving rise to a superoxide anion that further decomposes to reactive oxygen species. The reaction in question, which takes place in an aqueous solution, is as such not limited to the mitochondrial membrane where scavenging enzymes such as catalase and superoxide dismutase are located. With the experimental rate constant of 0.147 s-1, the dopamine autoxidation reaction is comparably as fast as the monoamine oxidase B catalyzed dopamine decomposition with a rate constant of 1 s-1. By using quantum chemical calculations, we demonstrated that the rate-limiting step is the formation of a hydroxide ion from a water molecule, which attacks the amino group that enters intramolecular Michael addition, giving rise to a pharmacologically inert aminochrome. We have shown that for dopamine stability on a time scale of days, it is essential that the pH value of the synaptic vesicle interior is acidic. The pathophysiologic correlates of the results are discussed in the context of Parkinson’s disease as well as the pathology caused by long-term amphetamine and cocaine administration.

Keywords: Dopamine, aminochrome, neurodegeneration, pH, Parkinson Disease, Reactive Oxygen Species, Oxidative Stress

Received: 27 Aug 2018; Accepted: 03 Dec 2018.

Edited by:

Karsten Hiller, Technische Universitat Braunschweig, Germany

Reviewed by:

Dietmar Fuchs, Innsbruck Medical University, Austria
Stefan Schulz, Technische Universitat Braunschweig, Germany  

Copyright: © 2018 Umek, Gersak, Vintar, Sostaric and Mavri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Janez Mavri, National Institute of Chemistry Slovenia, Ljubljana, Slovenia, janez.mavri@ki.si