Essential metals in health and disease.

In total, twenty elements appear to be essential for the correct functioning of the human body, half of which are metals and half are non-metals. Among those metals that are currently considered to be essential for normal biological functioning are four main group elements, sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca), and six d-block transition metal elements, manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn) and molybdenum (Mo). Cells have developed various metallo-regulatory mechanisms for maintaining a necessary homeostasis of metal-ions for diverse cellular processes, most importantly in the central nervous system. Since redox active transition metals (for example Fe and Cu) may participate in electron transfer reactions, their homeostasis must be carefully controlled. The catalytic behaviour of redox metals which have escaped control, e.g. via the Fenton reaction, results in the formation of reactive hydroxyl radicals, which may cause damage to DNA, proteins and membranes. Transition metals are integral parts of the active centers of numerous enzymes (e.g. Cu,Zn-SOD, Mn-SOD, Catalase) which catalyze chemical reactions at physiologically compatible rates. Either a deficiency, or an excess of essential metals may result in various disease states arising in an organism. Some typical ailments that are characterized by a disturbed homeostasis of redox active metals include neurological disorders (Alzheimer's, Parkinson's and Huntington's disorders), mental health problems, cardiovascular diseases, cancer, and diabetes. To comprehend more deeply the mechanisms by which essential metals, acting either alone or in combination, and/or through their interaction with non-essential metals (e.g. chromium) function in biological systems will require the application of a broader, more interdisciplinary approach than has mainly been used so far. It is clear that a stronger cooperation between bioinorganic chemists and biophysicists - who have already achieved great success in understanding the structure and role of metalloenzymes in living systems - with biologists, will access new avenues of research in the systems biology of metal ions. With this in mind, the present paper reviews selected chemical and biological aspects of metal ions and their possible interactions in living systems under normal and pathological conditions.