Physiologic function of the Wilson disease gene product, ATP7B

• Published in: The American journal of clinical nutrition Vol. 67; no. 5; pp. 982S - 987S
• Main Authors: Bingham, MJ, Ong, TJ, Summer, KH, Middleton, RB, McArdle, HJ
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.05.1998; American Society for Clinical Nutrition
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - physiology; Adenosine Triphosphate - metabolism; Animals; Biological and medical sciences; Biological Transport; Carrier Proteins - genetics; Carrier Proteins - physiology; Cation Transport Proteins; Copper - metabolism; Copper - physiology; Copper-transporting ATPases; Errors of metabolism; Hepatolenticular Degeneration - genetics; Hepatolenticular Degeneration - metabolism; Humans; Liver - metabolism; Liver - physiology; Medical sciences; Menkes Kinky Hair Syndrome - genetics; Menkes Kinky Hair Syndrome - metabolism; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Rats; Intracellular transport; Nervous system diseases; Membrane protein; Wilson disease; Digestive system; Enzyme; Liver; Adenosinetriphosphatase; Metabolic diseases; Review; Inorganic element; Enzymopathy; Biological activity; Genetic disease; Digestive diseases; Hydrolases; Copper; Carrier protein
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/67.5.982S

The genes responsible for Wilson disease and Menkes syndrome have been cloned and identified as copper ATPases. These enzymes form part of a large family of transporters, the P-type ATPases. Although copper ATPases share strong structural similarities with these other pumps, comparatively little is known about their physiologic function. In this review, we examine data relating to the Wilson disease protein, ATP7B, in the liver. We present evidence suggesting that ATP7B is located intracellularly, together with data suggesting that, at least in part, ATP7B may also be found on the canalicular membrane. We also examine the form of copper that the transporter recognizes. We then review data on the Long-Evans Cinnamon rat, a model for Wilson disease, and discuss what effect the Wilson disease mutation has on copper transport. Finally, we conclude that, although we have made major advances in our understanding of copper metabolism in the liver, there are still many questions awaiting answers.