The trace element is an essential component of numerous oxygen– and electron-transferring active groups. Iron deficiency leads to a decrease in the activity of the iron-dependent enzymes involved, especially oxidoreductases and monooxigenases.
Oxygen transport and storage
As an essential building block of hemoglobin, the main role of iron is to transport oxygen from the lungs to the site of terminal oxidation in tissues. Iron is also involved in the storage of oxygen in the form of myoglobin. As a single-chain heme protein, myoglobin increases the rate of diffusion of oxygen from erythrocytes (red blood cells) into the cytosol and mitochondria of muscle. Hemoglobin as well as myoglobin contain about 75% of the total body oxygen.
Electron transport
Important iron-containing fractions include the cytochromes of the mitochondrial respiratory chain. These are essential for electron transport, transferring electrons to molecular oxygen until water is formed. Iron serves as an electron acceptor in this process. Cytochrome systems, especially cytochrome c, also play a role in cellular energy supply, as they are required for the production of ATP – adenosine triphosphate, energy donor of the organism. Oxidation and reduction
- Ribonucleotide reductases – need iron to catalyze the step in DNA synthesis that determines the rate of the reaction
- Amino acid monooxigenases – the function of these iron-dependent enzymes is to accelerate reactions to form the serotonin precursor 5-hydroxytryptophan and the dopamine precursor L-dopa; serotonin and dopamine are important neurotransmitters in the central nervous system
- Cytochrome P450 family – mediate numerous reactions in the metabolism of xenobiotics (foreign substances) with the help of iron as an activating metal, are involved in the biosynthesis of steroid hormones, such as sex hormones and corticoids, vitamin D3, in the metabolism of drugs, aromatic hydrocarbons and in the synthesis of bile acid, among others
- Fatty acid desaturases – formation of unsaturated fatty acids.
- Lipoxigenases – synthesis of leukotrienes, which belong to the substance class of eicosanoids, are localized in leukocytes (white blood cells) and are associated with allergic or inflammatory reactions of the body.
- Iron-containing metallo-enzyme complexes, such as peroxidases, catalases and oxygenases – transfer hydrogen to hydrogen peroxide, contributing to the disposal of oxygen radicals.
- NO synthases and peroxidases, except glutathione peroxidases – affect vasodilation (dilation of blood vessels by relaxation of vascular smooth muscle), neurotransmission – communication between neurons through synapses – and immune status
- Oxygen transferases – provide for the transfer of oxygen in intermediary metabolism.
- Iron-containing hydroxylases – regulate detoxification processes in the body.
- Succinate dehydrogenase of the citrate cycle – catalyzes the oxidation of succinate to fumarate.
- Akonitases in the citrate cycle of mitochondria – contain iron as a loosely bound cofactor – iron-sulfur center – and play an essential role as a catalyst of the reversible reaction of citrate to isocitrate
Iron-dependent enzymes also include guanylate cyclases – cGMP as a second messenger – and aminophosphoribosyltransferases. The latter are essential for purine synthesis, catalyzing the step that determines the reaction rate.
Prooxidant action
Free iron ions are able to catalyze the Fenton reaction, with superoxide and hydrogen peroxide reacting to form free, reactive radicals that have been associated with increased oxidative stress and premature cellular aging. Only the transport protein transferrin has antioxidant properties. By binding iron, it protects cells and tissues from free iron ions that exhibit aggressive oxidative effects.
Collagen synthesis
Iron is an essential trace element for the hydroxylation of polypeptide chains, making it essential for the proper formation as well as regeneration of bone, cartilage and connective tissue.
High iron stores as a potential risk factor
Free iron ions exhibit toxic effects.As prooxidants, they are associated with the development of cardiovascular diseases – such as coronary heart disease (CHD; disease of the coronary vessels) resulting in myocardial infarction (heart attack) – and neurodegenerative diseases – for example Alzheimer’s disease or Parkinson’s disease. Furthermore, iron probably plays a role as a limiting nutrient for growth and replication of tumor cells. A study from the USA has confirmed that elevated serum iron levels are associated with an increased risk of tumor disease. As an underlying mechanism, it is discussed that iron promotes oxidative stress via its key catalytic function in the formation of cytotoxic oxygen and hydroxy radicals, for example in the course of the Fenton and Haber-Weiss reactions. To prevent such diseases, increased iron intakes as well as increased iron stores should be avoided. Iron overloads occur, for example, as a result of drinking water with a high iron content, iron cookware, frequent blood transfusions, excessive intake of iron supplements, and as a result of chronic alcoholism or increased consumption of readily absorbable sources of iron – for example heme iron – from foods of animal origin. In this regard, studies have found a positive correlation between cardiovascular risk – particularly the risk of myocardial infarction (heart attack) and heme iron intake, but not with non-heme iron or total iron intake. Hereditary hemochromatosis is an “iron storage disease” due to excessive, uncontrolled gastrointestinal absorption. Individuals with this autosomal recessive disease have an increased risk of hepatocellular carcinoma. In addition, affected individuals suffer from weakness, brown-gray skin pigmentation, or arthritis, among other symptoms. In the later stages, myocardial damage (damage to the heart muscles), diabetes mellitus or liver cirrhosis may occur. Liver cirrhosis is the final stage of various chronic liver diseases, characterized by the death of liver cells, resulting in nonfunctional, nodular connective tissue. In addition to liver carcinoma, hemochromatosis patients may also develop other tumors, such as mammary carcinoma (breast cancer) or colorectal carcinoma (colon and rectal carcinoma). Important Notice. Before starting to take an iron supplement, the serum ferritin level should always be determined by the physician to detect an iron deficiency! Persons with elevated ferritin concentrations should not take iron supplements under any circumstances. There is an additional risk if such individuals regularly consume vitamin-containing supplements. Vitamins A, C, and E exhibit prooxidant effects when iron depots are elevated and directly cause reduction to unbound free iron (Fe2+) for the Fenton reaction.
