Extracellular Glutathione Peroxidase:A Distinct Selenoprotein

Abstract

Disease states in animals and humans have been attributed to selenium deficiency because they can be prevented or reversed by the addition of selenium to the diet (1 – 7). In patients undergoing chronic parenteral nutrition, selenium deficiency has been associated with heart failure (5–7) muscle pain (8) and muscle weakness (9). A role for selenium in intracellular metabolism of mammals was first realized in 1973 with the discovery that selenium was part of the enzyme glutathione peroxidase (10) and was essential for its activity (11). Selenium in this protein is in the form of selenocysteine (12), which gets specifically incorporated in response to the opal suppressor codon UGA (13,14). Except for the recent description of (type 1) 5’ iodothyronine deiodinase as a selenocysteine-containing enzyme (15), the only other selenoprotein with a known function in mammalian tissue is the selenium-dependent glutathione peroxidase. At least three different glutathione peroxidases have been described:A cytoplasmic cellular form found within all cells tested (16), a membrane form described in porcine heart (17) and rat liver (18), and an extracellular form described by us and others (19 – 21). The enzymes are structurally, functionally, and antigenically distinct from each other. This manuscript will describe the studies that led to the recognition of the extracellular form of glutathione peroxidase as a distinct protein and current information as to its structure, sites of synthesis and secretion, and potential role in extracellular metabolism.