This Article Full Text Full Text (PDF) All Versions of this Article: 52/5/811    most recent HYPERTENSIONAHA.108.117770v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rudolph, V. Articles by Freeman, B. A. Search for Related Content PubMed PubMed Citation Articles by Rudolph, V. Articles by Freeman, B. A. Related Collections Animal models of human disease Related Article

(Hypertension. 2008;52:811.)
© 2008 American Heart Association, Inc.

Editorial Commentaries

Copper Trafficking and Extracellular Superoxide Dismutase Activity

Kinky Hair, Kinky Vessels

Volker Rudolph; Tanja K. Rudolph; Bruce A. Freeman

From the Department of Pharmacology & Chemical Biology (V.R., T.K.R., B.A.F.), University of Pittsburgh, Pa; and the Department of Cardiology (V.R., T.K.R.), University Heart Center Hamburg, Germany.

Correspondence to Bruce A. Freeman, PhD, Department of Pharmacology & Chemical Biology, E1340 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop St, Pittsburgh, PA 15261. E-mail freerad@pitt.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In 1962, Menkes et al¹ 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.² 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 tyrosinase of patients with Menkes disease.³ 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 . . . [Full Text of this Article]

Related Article:

Role of Menkes ATPase in Angiotensin II-Induced Hypertension: A Key Modulator for Extracellular Superoxide Dismutase Function

Zhenyu Qin, Maria Carolina Gongora, Kiyoshi Ozumi, Shinichi Itoh, Kamran Akram, Masuko Ushio-Fukai, David G. Harrison, and Tohru Fukai
Hypertension 2008 52: 945-951. [Abstract] [Full Text] [PDF]