It is estimated that over a third of human proteins are bound to a metal (i.e., metalloproteins). Certain metals act as cofactors, while others are integral components of the cofactors (e.g., cobalt in cobalamin). The deficiency of a metal can then lead to decreased enzymatic activities of the respective metalloenzymes, as happens in copper deficiency due to Menkes disease, or zinc deficiency in acrodermatitis enteropathica. On the other hand, metal accumulation can result in other disorders. Metal toxicity is believed to occur through the formation of excess radical oxygen species via the Fenton reaction; examples include iron accumulation in hemochromatosis and copper accumulation in Wilson disease. The metal overload in this group of disorders can occur via either deficiency of a metal transporter-as in hypermanganesemia with dystonia, polycythemia and cirrhosis due to SLC30A10 mutations- or impaired enzyme activity because the metal fails to be incorporated into the apoenzyme. For example, in aceruloplasminemia, mutations in apo-cerulosplasmin impair the ferroxidase activity of ceruloplasmin and, as a consequence, lead to accumulation of ferrous iron. In this chapter, we review the different genetic conditions associated with altered metal metabolism.
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
Tel.: +1 703 830 6300
Fax: +1 703 830 2300 firstname.lastname@example.org
(Corporate matters and books only) IOS Press c/o Accucoms US, Inc.
For North America Sales and Customer Service
West Point Commons
Lansdale PA 19446
Tel.: +1 866 855 8967
Fax: +1 215 660 5042 email@example.com