Disorders of Copper, Zinc and Iron Metabolism

Copper, zinc and iron are essential cationic trace elements. They are transferred and utilized as inorganic ions and transported by specific carriers across membranes. They also require carriers to maintain their solubility within the intra- and extracellular compartments. Their homeostasis is controlled primarily by the gastrointestinal tract and the liver. Each of these elements has its own specific function and metabolic control [1]. The diagnosis of deficiencies or excesses of copper and zinc can be difficult, since no single test reliably indicates whether an individual is at risk. The clinical state, homeostatic mechanisms, metabolism and tissue distribution all have to be considered for the interpretation of data [1]. 

Copper is a component of many biologically important enzymes, such as cytochrome oxidase, superoxide dismutase, tyrosinase, dopamine-beta-hydroxylase, lysyl oxidase and ceruloplasmin. 

The inborn errors of copper, zinc and iron metabolism are related to their transport across membranes and within the cells. 

Treatment is directed towards reducing the amount of copper in the body [4, 5]. Measuring urinary copper and zinc can monitor the efficacy of chelation and/or zinc therapy. With adequate treatment the prognosis is good. In severe liver damage, liver transplantation might be necessary [5]. 

However, in fibroblasts there were no biochemical differences between MD and OHS [8]. Clinically, OHS must be differentiated from X-linked recessive Ehlers/Danlos syndrome type V. The latter is a milder disease with mild laxity of the skin and joints [12, 15]. 

---

In many crucial biological processes, such as oxygen transport, electron transport, intermediary metabolism, metals play an important part. Therefore, disorders of metal homeostasis, metal bioavailability or toxicity caused by metal excess, are responsible for a large number of human diseases. We have already mentioned disorders of iron metabolism (see Chapter 7) and of copper metabolism (see Chapter 14). The important role, particularly of redox metals such as copper and iron, and also of zinc, in neurodegenerative diseases, such as Parkinson s disease, Alzheimer s disease, etc. has also been discussed (see Chapter 18). We will not further discuss them here. 

An excess of zinc will cause problems in humans. Excessive doses can lead to biochemical control system damage, while doses slightly higher than optimal can cause disorders in iron and copper metabolism, resulting in incurable anemia, decrease in activity of zinc protein enzymes, and pancreas and kidney damage (Boularbah et ah, 1999 Seiler et ah, 1994). Increased levels of zinc have been observed in nuclei of neoplastic cells and in cases of acute dental caries, however its role in these diseases has not been explained. 

Certain inherited diseases are associated with abnormal trace metal metabolism, and this may be linked to MT synthesis, either directly or indirectly. Zinc, copper, and iron are the target elements in several diseases, and their concentrations may be altered in disorders of the central nervous system or other physiological systems, including Alzheimer-type dementia, amyotrophic lateral sclerosis, acrodermatitis enteropathica, biliary cirrhosis, Wilson s and Menke s diseases (Bremner 1987), epi-... 

Some reports found an increase in liver zinc concentrations in chronic liver disease. An increase in copper and zinc liver concentrations was found in Canadian children with chronic cholestasis (Phillips et al., 1996). Another case report described the increase in zinc concentration in hepatic tissue of a child with hepatosplenomegaly and symptoms of zinc deficiency, and the authors speculated about the existence of a zinc metabolism disorder (Sampson et al, 1997). A study that investigated the concentration of metals in liver tissue of adults with hereditary hemochromatosis found an increase in zinc in the liver parenchyma. The authors suggested that the concurrent increase in iron and zinc might be explained by the greater intestinal absorption of these metals (Adams et al., 1991). 

---