A 30-year-old woman presents with hemochromatosis-like features, low ceruloplasmin, Kayser-Fleischer rings, and liver cirrhosis. Ferrous iron (Fe²⁺) is elevated because ceruloplasmin-mediated ferroxidase activity is impaired. Which copper transport protein is defective in Wilson's disease?
- A Menkes ATPase (ATP7A) — responsible for copper absorption in intestinal enterocytes
- B Copper transporter 1 (CTR1) — responsible for intracellular copper uptake from the portal circulation
- C Wilson's disease ATPase (ATP7B) — responsible for copper incorporation into ceruloplasmin and biliary copper excretion in hepatocytes ✓
- D Hephaestin — a copper-containing ferroxidase that is homologous to ceruloplasmin and expressed in enterocytes
Explanation
Wilson's disease is caused by autosomal recessive loss-of-function mutations in ATP7B, a P-type copper-transporting ATPase expressed primarily in hepatocytes. ATP7B has two functions: incorporation of copper into apoceruloplasmin in the Golgi apparatus (producing active ceruloplasmin with ferroxidase activity) and transport of excess copper into bile for excretion. Its deficiency causes copper accumulation in liver, brain, and cornea (Kayser-Fleischer rings), and low ceruloplasmin (since apoceruloplasmin secreted without copper is rapidly degraded). Menkes disease involves ATP7A (intestinal/general copper export). Hephaestin is a ferroxidase for iron, not the defective protein in Wilson's disease.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.