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Mechanism of the manganese-catalyzed autoxidation of dopamine
1Department of Chemistry, University of Memphis, Tennessee 38152, USA.
Abstract:
Manganese is an essential trace element for human metabolism, but at higher concentrations it is a potent neurotoxin that presents clinical symptoms similar to those of Parkinson's disease. Since the toxicity of manganese may be related to its ability to accelerate the oxidation of catecholamines, we have examined the effect of aqueous Mn2+ on the formation and decay of the dopamine semiquinone radical ion. ESR spectroscopy was used to measure the kinetics of the disappearance of the semiquinone radical spectrum and the simultaneous appearance of the six-line spectrum of aqueous Mn2+ in Tris buffer. From the proposed mechanism for the autoxidation of dopamine to the quinone, the rate expression for semiquinone radical disappearance has the functional form -rate = k'[D(OH)2][Mn2+] at constant pH and molecular oxygen concentration, while the pH dependence is given by -log(rate) = log(constant) + (2 x pH), in agreement with the experimental results. The autoxidation of dopamine is catalyzed by manganese through the formation of a highly reactive complex. The effect of manganese is due to the fact that it can participate in a redox cycle which involves intramolecular electron transfer between manganese and the dopamine ligand.
Insights
Manganese (Mn2+) accelerates the oxidation of dopamine, a key neurotransmitter, potentially explaining its neurotoxicity. This study reveals manganese catalyzes dopamine oxidation via a reactive complex and redox cycling.
Area of Science:
- Biochemistry
- Neuroscience
- Environmental Health
Background:
- Manganese is essential for metabolism but toxic at high levels, mimicking Parkinson's disease symptoms.
- Manganese neurotoxicity is linked to accelerated oxidation of catecholamines like dopamine.
Purpose of the Study:
- To investigate the effect of aqueous Mn2+ on dopamine semiquinone radical ion formation and decay.
- To elucidate the mechanism by which manganese influences dopamine oxidation.
Main Methods:
- Electron Spin Resonance (ESR) spectroscopy was employed.
- Kinetics of semiquinone radical disappearance and Mn2+ spectrum appearance were measured in Tris buffer.
Main Results:
- Manganese (Mn2+) significantly catalyzes dopamine autoxidation.
- The rate of semiquinone radical disappearance follows a specific rate expression dependent on Mn2+ concentration and pH.
- A reactive complex formation and redox cycling involving intramolecular electron transfer between manganese and dopamine were identified.
Conclusions:
- Manganese accelerates dopamine oxidation by forming a reactive complex and participating in a redox cycle.
- This catalytic effect of manganese on dopamine oxidation provides a biochemical basis for its neurotoxic effects.
- Understanding this mechanism is crucial for addressing manganese-induced neurotoxicity.