Copper Trafficking and Extracellular Superoxide Dismutase Activity Kinky Hair, Kinky Vessels

摘要

In 1962, Menkes et al first described a pediatric disorder characterized by hypopigmented brittle hair, doughy skin, connective tissue fragility, failure to thrive, progressive neurological damage, and various defects of the arterial wall. This was termed "kinky hair syndrome" and later was found to be associated with a disturbance in copper metabolism due to mutations in the ATP7A gene.The ATP7A (or Menkes ATPase) is 1 of 2 membrane-bound copper-transporting ATPases (ATP7A and ATP7B) essential for controlling intracellular copper homeostasis. ATP7A is of particular importance for the transfer of copper through the membrane of the trans-Golgi network and hence is important for the so-called secretory pathway of copper. In Menkes syndrome, in which the function of the ATP7A transporter is disturbed, systemic copper levels are low because copper export from enterocytes is greatly impaired and copper thus accumulates in the intestine. A critical manifestation of impaired ATP7A function is the limited incorporation of copper, an essential catalytic residue in a variety of enzymes. An early example of this defect was highlighted by insufficient insertion of copper into the tyrosi-nase of patients with Menkes disease. Tyrosinase is the rate-limiting enzyme of melanin formation with defects in its activity leading to low melanin levels in skin, albinism, and the hypopigmentation that is a clinical hallmark of Menkes syndrome. The study by Qin et al,4 published in the current issue of Hypertension, is of interest and significance because a critical linkage has been made between cardiovascular function and the biochemical defects in copper trafficking that are a hallmark of altered ATP7A function.