Abstract
All living organisms require dietary copper for continued growth and development. This nutritional requirement arises from the essential role of the metal in the function of cuproenzymes, which play a critical role in the biochemistry of oxygen activation, not only for energy transduction (e.g. ATP synthesis by cytochrome oxidase or dopamine α-hydroxilation), but also in futile oxygen activation for chemical transformation of metabolic intermediates (e.g. H2O2-producing amine oxidase) (Linder and Hazegh-Azam, 1996). However, excess copper — as exemplified by non-physiological conditions such as experimental copper overload or by clinical conditions related to impaired metal transport as Wilson disease — mediates free radical production and direct oxidation of cellular components. Reduction of copper by physiological reductants triggers a series of radical reactions. Autoxidation of Cu+ yields, which dismutes to H2O2, reacting in turn with Cu+ with the ultimate production of OH, the actual agent of oxidative damage (Fridovich, 1995). In order to prevent and counterbalance such reactions, living organisms have evolved various mechanisms of defense. These involve, besides the direct sequestering of copper and other metal ions by metallothioneins, so that they never exist in the free form, a complex system of oxyradicals interception including several enzymatic and non-enzymatic scavengers. Among the species involved in oxyradicals interception, a key role is played by Cu,Zn Superoxide dismutase (SOD) where copper scavenges the primary source of damage (see above) at diffusion-limited rate.
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Carrì, M.T., Battistoni, A., Ferri, A., Gabbianelli, R., Rotilio, G. (1999). A Study of the Dual Role of Copper in Superoxide Dismutase as Antioxidant and Pro-Oxidant in Cellular Models of Amyotrophic Lateral Sclerosis. In: Leone, A., Mercer, J.F.B. (eds) Copper Transport and Its Disorders. Advances in Experimental Medicine and Biology, vol 448. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4859-1_18
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DOI: https://doi.org/10.1007/978-1-4615-4859-1_18
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