Copper and neurological function.
The role of copper in maintaining normal neurological function has been examined in animals copper-deficient by dietary means, and in the genetic disorders of copper homeostasis -- Menkes' kinky-hair disease in humans and the mottled (Mo) mutants in the mouse. With the exception of the disorder in Mo mice, reduced myelination is a constant feature of these copper diseases but there is otherwise a lack of conformity in the structural defects produced in different species. Dietary copper-deficient animals show a reduction in noradrenaline and dopamine concentrations, together with a depressed tyrosine 3-monooxygenase activity (EC 1.14.16.2). Noradrenaline concentrations are also reduced in brain tissue of Mo mice and this reduction is associated with a decrease in the vivo activity of the copper metalloenzyme, dopamine beta-monooxygenase (EC 1.14.17.1). Many tissues contain potent inhibitors of dopamine beta-monooxygenase activity, and assays of this enzyme have utilized cupric ions to inactivate these inhibitors. The elevated in vitro activities of dopamine beta-monooxygenase obtained for both Mo brain and adrenal tissue may therefore reflect either a reduced inactivation of these endogenous inhibitors in the intact animal or the activation in vitro of apoenzyme. Concentrations of dopamine and tyrosine 3-monooxygenase are unchanged in Mo mice. The reduction in dopamine and tyrosine 3-monooxygenase activity in dietary copper-deficient animals may therefore reflect neuronal loss rather than reduced catalytic activity of the catecholamine biosynthetic pathway. The possible effects of depressed activities of cytochrome c oxidase (EC 1.9.3.1) and superoxide dismutase (EC 1.15.1.1) in the development of neurological dysfunction are also discussed, and attention is drawn to the possible significance of the elevated uptake of neutral amino acids, especially tyrosine and tryptophan, by Mo brain tissue.
D000375:Aging; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002395:Catecholamines / Q000096:biosynthesis; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism
D000596:Amino Acids; D002352:Carrier Proteins; D002395:Catecholamines; D003300:Copper