Physiologic function of the Wilson disease gene product, ATP7B

Am J Clin Nutr. 1998 May;67(5 Suppl):982S-987S. doi: 10.1093/ajcn/67.5.982S.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / physiology*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Biological Transport
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cation Transport Proteins*
  • Copper / metabolism*
  • Copper / physiology
  • Copper-Transporting ATPases
  • Hepatolenticular Degeneration / genetics*
  • Hepatolenticular Degeneration / metabolism
  • Humans
  • Liver / metabolism*
  • Liver / physiology
  • Menkes Kinky Hair Syndrome / genetics
  • Menkes Kinky Hair Syndrome / metabolism
  • Rats

Substances

  • Carrier Proteins
  • Cation Transport Proteins
  • Copper
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • ATP7B protein, human
  • Copper-Transporting ATPases