Iron, metalloenzymes and cytotoxic reactions.
There is considerable evidence implicating iron and other redox-active transition metals as progenitors of reactive intermediates of oxygen (ROI), molecules which lead to oxidative stress and contribute to various neurodegenerative processes. An important aspect of such metal-mediated damage to biomolecules is the site-specific nature of such pathological activity. Iron sequestering molecules, such as ferritin, transferrin, lactotransferrin, melanotransferrin, hemosiderin and heme can serve as cytoprotectants against metal-mediated oxidant damage. Metalloenzymes also constitute an important group of iron sequestering molecules. Metalloenzyme-catalyzed reactions in which metal ions at the enzyme active site undergo redox-cycling in association with O2 are site-specific in nature, and may represent a potential source of ROI-mediated damage to biomolecules. Dysregulation of brain iron and alterations in the levels of metalloenzymes involved in reactions with O2 derived molecules can contribute to neuronal damage. Iron may increase the cytotoxicity of neuronal dopamine by increasing its rate of oxidation to quinones and semiquinones, thereby reducing the level of this neurotransmitter. Interestingly, dopamine also may play an important role in the maintenance of transition-metal homeostasis as an iron chelator, since it can form both catecholate and hydroxamate groups, molecules employed by many microorganisms to sequester iron.
Nappi
A J
AJ
Department of Biology, Loyola University Chicago, IL 60626, USA. anappi@orion.it.luc.edu
Vass
E
E
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D008670:Metals / Q000378:metabolism
D000975:Antioxidants; D002395:Catecholamines; D003603:Cytotoxins; D007502:Iron Chelating Agents; D008670:Metals; D007501:Iron; D008666:Metalloendopeptidases