Mechanism of the Manganese-Catalyzed Autoxidation of Dopamine

Lloyd, Roger V.

doi:10.1021/tx00043a015

Cited by 65 publications

(46 citation statements)

References 26 publications

(37 reference statements)

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“…Again, we observed that MnPO 4 was the most potent Mn compound tested. Consistent with the above mechanism, Lloyd (1995) provided evidence for a redox mechanism in which Mn 2+ forms a complex with DA (and other 3,4-hydroxylated catecholamines) that is oxidized to a DA-Mn complex with a Mn 3+ valence state (see Fig. 9).…”

Section: Discussionsupporting

confidence: 60%

“…Thus, it is possible that MnPO 4 is more efficient at forming the DA-Mn complex, and perhaps, the Dopac-Mn complex, (i.e., has a greater affinity for 3,4-hydroxylated catecholamines) than MnCl 2 or MnSO 4 ; hence, oxidizing catecholamines more effectively. Figure 9, which is modified from Lloyd (1995), highlights the proposed mechanism of DA oxidation catalyzed by Mn and the interaction of different Mn ions with DA.…”

Section: Discussionmentioning

confidence: 99%

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Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Sistrunk

Ross

Filipov

2007

Environmental Toxicology and Pharmacology

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Following combustion of fuel containing the additive methylcyclopentadienyl-manganesetricarbonyl (MMT), manganese phosphate (MnPO 4 ) and manganese sulfate (MnSO 4 ) are emitted in the atmosphere. Manganese chloride (MnCl 2 ), another Mn 2+ species, is widely used experimentally. Using rat striatal slices, we found that MnPO 4 decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl 2 or MnSO 4 ; antioxidants were partially protective. Also, both MnCl 2 and MnPO 4 (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO 4 will be more potent in forming aminochrome than MnCl 2 or MnSO 4 which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO 4 in particular, is the generation of reactive DA intermediates.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Sistrunk

Ross

Filipov

2007

Environmental Toxicology and Pharmacology

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“…Manganese can adopt different valences and is a powerful oxidant as the trivalent species (9). Together with dopamine, manganese can accelerate oxidation-reduction reactions, producing reactive oxidative molecules such as hydrogen peroxide and superoxide free radicals; this potentially explains the dopaminergic neurotoxicity seen in chronic manganese poisoning and the relief of symptoms by the administration of L-dopa in some patients (10)(11)(12)(13)(14). With relevance to the current case, derangements in dopamine metabolism have also been invoked as a mechanism underlying the syndrome of attention deficit hyperactivity disorder in some children (15,16).…”

Section: Discussionmentioning

confidence: 99%

A child with chronic manganese exposure from drinking water.

Woolf

Wright

Amarasiriwardena

et al. 2002

Environ Health Perspect

149

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The patient's family bought a home in a suburb, but the proximity of the house to wetlands and its distance from the town water main prohibited connecting the house to town water. The family had a well drilled and they drank the well water for 5 years, despite the fact that the water was turbid, had a metallic taste, and left an orange-brown residue on clothes, dishes, and appliances. When the water was tested after 5 years of residential use, the manganese concentration was elevated (1.21 ppm; U.S. Environmental Protection Agency reference, < 0.05 ppm). The family's 10-year-old son had elevated manganese concentrations in whole blood, urine, and hair. The blood manganese level of his brother was normal, but his hair manganese level was elevated. The patient, the 10-year-old, was in the fifth grade and had no history of learning problems; however, teachers had noticed his inattentiveness and lack of focus in the classroom. Our results of cognitive testing were normal, but tests of memory revealed a markedly below-average performance: the patient's general memory index was at the 13th percentile, his verbal memory at the 19th percentile, his visual memory at the 14th percentile, and his learning index at the 19th percentile. The patient's free recall and cued recall tests were all 0.5-1.5 standard deviations (1 SD = 16th percentile) below normal. Psychometric testing scores showed normal IQ but unexpectedly poor verbal and visual memory. These findings are consistent with the known toxic effects of manganese, although a causal relationship cannot necessarily be inferred. Key words: ADHD, attention deficit hyperactivity disorder, manganese, manganese exposure, water, water pollution.

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“…Moreover, levodopa is contraindicated in manganism, as Mn catalyzes dopamine autooxidation to toxic quinones and semiquinones (Graham 1984;Lloyd 1995;Parenti et al 1988). According to some studies (Discalzi et al 2000;Herrero Hernández et al 2003;Herrero Hernández et al 2006;Ky et al 1992;Ono et al 2002;Penalver 1957) chelating treatment can reverse manganese poisoning with persistent clinical benefit for many years (Herrero Hernández et al 2003;Herrero Hernández et al 2006;Jiang et al 2006).…”

Section: Treatmentmentioning

confidence: 99%

Manganese and its Role in Parkinson’s Disease: From Transport to Neuropathology

et al. 2009

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Abstract:The purpose of this review is to highlight recent advances in the neuropathology associated with Mn exposures. We commence with a discussion on occupational manganism and clinical aspects of the disorder. This is followed by novel considerations on Mn transport (see also chapter by Yokel, this volume), advancing new hypotheses on the involvement of several transporters in Mn entry into the brain. This is followed by a brief description of the effects of Mn on neurotransmitter systems that are putative modulators of dopamine (DA) biology (the primary target of Mn neurotoxicity), as well as its effects on mitochondrial dysfunction and disruption of cellular energy metabolism. Next, we discuss inflammatory activation of glia in neuronal injury and how disruption of synaptic transmission and glial-neuronal communication may serve as underlying mechanisms of Mn-induced neurodegeneration commensurate with the cross-talk between glia and neurons. We conclude with a discussion on therapeutic aspects of Mn exposure. Emphasis is directed at treatment modalities and the utility of chelators in attenuating the neurodegenerative sequelae of exposure to Mn. For additional reading on several topics inherent to this review as well as others, the reader may wish to consult Aschner and Dorman (Toxicological Review 25:147-154, 2007) and Bowman et al. (Metals and neurodegeneration, 2009).

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Mechanism of the Manganese-Catalyzed Autoxidation of Dopamine

Cited by 65 publications

References 26 publications

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

A child with chronic manganese exposure from drinking water.

Manganese and its Role in Parkinson’s Disease: From Transport to Neuropathology

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