GENES REGULATING COPPER-METABOLISM

The metabolism of Cu is intimately linked with its nutrition. From gut to enzymes, Cu bioavailability to key enzymes and other components op erates through a complex mechanism that uses transport proteins as wel l as small molecular weight ligands. Steps in Cu transport through the blood, absorption by cells, and incorporation into enzymes are slowly being understood. Cloning and sequencing of the genes for Menkes dise ase and Wilson disease has shown that membrane-bound enzymes analogous to Cu-ATPases in prokaryotes are equally important to Cu transport an d homeostasis in mammalian cells. The primary structure of the mammali an Cu-ATPases has been deduced from cDNAs from tissues and organs. It now appears that mammalian Cu-ATPase have tissue and developmental spe cificity. In this review, we will focus on the Cu-ATPase that has been identified with Menkes disease. An emphasis will be placed on the exi stence of multiple forms of the ATPase and some indication as to how t he different isoforms befit their role in the normal physiology of cop per, specifically transmembrane transport and maintenance of a favorab le internal cellular environment.