Molecular genetics of intracellular copper transport

Copper is essential for life processes as cofactor for many vital cuproenzy mes, yet it is extremely toxic in excess. Efficient mechanisms have been de veloped to recruit and deliver copper to enzymes and for excretion of surpl us metal. Imbalance of copper homeostasis is manifested in two human illnes ses, Menkes disease and Wilson disease, which are both caused by defective export mechanisms that involve ATP7A and ATP7B, respectively. Severe defici ency of copper is mimicked by Menkes disease, whereas Wilson disease leads to toxic accumulations of the metal. The copper export pumps are energy req uiring trans porters possessing a number of unique molecular features. Besi des domains typical for P-type ATPases, several heavy metal specific sites have been described in the copper subfamily of the ATPases. Identification of disease-causing mutations will help to define structural determinants of normal copper pump function. In this review we discuss the current knowled ge about the human copper pumps, ATP7A and its homologue ATP7B. J. Trace El em. Exp. Med. 12:297-313 1999. (C) 1999 Wiley-Liss, Inc.