Abstract
Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost all cellular and physiological functions. The diversity of the activity and function of iron and its associated pathologies is based on bond formation with adjacent ligands and the overall structure of the iron complex in proteins or with other biomolecules. The control of the metabolic pathways of iron absorption, utilization, recycling and excretion by iron-containing proteins ensures normal biologic and physiological activity. Abnormalities in iron-containing proteins, iron metabolic pathways and also other associated processes can lead to an array of diseases. These include iron deficiency, which affects more than a quarter of the world’s population; hemoglobinopathies, which are the most common of the genetic disorders and idiopathic hemochromatosis. Iron is the most common catalyst of free radical production and oxidative stress which are implicated in tissue damage in most pathologic conditions, cancer initiation and progression, neurodegeneration and many other diseases. The interaction of iron and iron-containing proteins with dietary and xenobiotic molecules, including drugs, may affect iron metabolic and disease processes. Deferiprone, deferoxamine, deferasirox and other chelating drugs can offer therapeutic solutions for most diseases associated with iron metabolism including iron overload and deficiency, neurodegeneration and cancer, the detoxification of xenobiotic metals and most diseases associated with free radical pathology.
Highlights
Iron, copper, zinc, cobalt, chromium, manganese, molybdenum and selenium are essential metal ions and nutrients, which play an important role in maintaining normal healthy living in humans.Deficiencies or excesses of these metal ions, as well as abnormalities in their metabolism may cause serious diseases and mortality.The important role of these essential metal ions is an integral part of enzymes and proteins, as well as that of transcription factors and other co-factors which secure the normal growth and development of the body
Appropriate therapeutic interventions could decrease the extent of unwanted negative health implications and may treat diseases associated with abnormalities related to iron, iron-containing proteins and associated metabolic pathways
The complete removal of excess iron from transfused iron loaded thalassemia patients can be achieved using selective combinations of L1 and DFO [107,108,109,110,111]. This combination appears to be effective in the removal of excess iron in other categories of iron loaded patients and is recommended as the safest and most effective combination protocol of intensive chelation for iron removal in heavily iron loaded patients [110,111]
Summary
Copper, zinc, cobalt, chromium, manganese, molybdenum and selenium are essential metal ions and nutrients, which play an important role in maintaining normal healthy living in humans. Abnormalities in iron homeostasis, iron-containing proteins and iron metabolic pathways can lead to diseases such as iron deficiency, which affects more than a quarter of the world’s population and idiopathic hemochromatosis, which is a genetic disease affecting one in ten people of the Caucasian population [5,6,7] Another major category of related diseases are the hemoglobinopathies, which are the most common group of genetic disorders in humans [8]. Many factors can influence the structure and biochemical functions of protein or non-protein iron complexes in vivo, leading to changes in biologic activity Some of these interactions may include other ligands, metal ions, anions, free radicals and other reactive oxygen or nitrogen species, chelators, etc. The molecular characteristics and properties of iron, chelators, chelating drugs, chelator metal complexes, as well as factors involved in modifying their activity, is discussed in the biochemical and clinical context with major emphasis on the prospects of understanding and treating relevant clinical conditions
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