J Camakaris

Menkes’ and Wilson’s Diseases: Genetic Disorders of Copper Transport

Copper is an essential element required by a number of important enzymes, including lysyl oxidase, cytochrome c oxidase, superoxide dismutase, and dopamine β-hydroxylase. Copper deficiency during development can prove lethal to developing mammals, and the multiple-organ-system effects can be explained by the reduced activity of these important enzymes. The severity of copper deficiency is illustrated by the lethal X-linked genetic disorder of copper transport, Menkes’ disease (MD). The molecular basis of this disease will be discussed in this chapter. The same properties that make copper a useful element for the redox reactions carried out by enzymes, render it dangerous in a free ionic state. Free copper has the potential to catalyze the formation of the highly reactive hydroxyl radicals, which damage many cell components, including membranes, proteins, and nucleic acids (Kumar et al. 1978). All organisms must have developed mechanisms for supplying copper to essential enzymes without damaging cellular constituents. It is most probable that this delivery is achieved by maintaining the copper in a complex at all times. Thus the Cu ion must be transferred from one complex to another as it moves within cells or between one compartment of the body to another. This movement of copper can be likened to a pathway; the various molecules involved in complexing and transferring copper form the steps of this pathway. The challenge for current research in copper transport is to identify these molecules and understand how the regulation of their concentrations and activity maintains copper supplies within acceptable ranges in the face of widely varying dietary intakes.