Metabolic Brain Disease

, Volume 7, Issue 3, pp 139–146 | Cite as

Differential effects of metal ions on type a and type B monoamine oxidase activities in rat brain and liver mitochondria

  • Thomas K. C. Leung
  • Louis Lim
  • James C. K. Lai
Original Contributions


To investigate the hypothesis that neurotoxic metals can exert their toxicity through the direct inhibition of monoamine oxidases (MAOs), the effects of several neurotoxic metal ions on type A (MAO-A) and type B (MAO-B) monoamine oxidase activities in rat forebrain nonsynaptic mitochondria and rat liver mitochondria were studied. At pathophysiological levels (10–100 μM), Cu2+ and Cd2+ are good inhibitors of brain mitochondrial MAO-A and, to a lesser extent, liver mitochondrial MAO-A. The inhibition of MAO-B activities in brain and liver mitochondria by Cu2+ and Cd2+ is only detected at the higher end of the concentration range (i.e., 50–100 μM). At the pathophysiological level of 0.5 mM, Al3+ only inhibits brain mitochondrial MAO-A but at the higher level of 2.5 mM, it inhibits both forms of MAO in brain as well as liver mitochondria. Even at toxic levels (e.g., 5 mM), neither Mn2+ nor Li+ inhibits the activities of MAO-A and MAO-B in brain and liver mitochondria. Our results are consistent with the hypothesis that some neurotoxic metals can exert their toxicity through the direct inhibition of the isoforms of MAO. Our data also suggest that the selective inhibition of brain MAO-A by Cu2+ and Cd2+ may assume pathophysiological importance in the neurotoxicity of copper and cadmium.

Key words

metal toxicity monoamine oxidases metal inhibition of monoamine oxidases 


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Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Thomas K. C. Leung
    • 1
  • Louis Lim
    • 1
  • James C. K. Lai
    • 2
  1. 1.Department of Neurochemistry, Institute of NeurologyUniversity of London, Queen SquareLondon WC1N 3BGUK
  2. 2.Department of Pharmaceutical Sciences and Center for Toxicology ResearchCollege of Pharmacy, Idaho State UniversityPocatelloUSA

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