Iron

• Iron plays a central role in the metabolism of all cells, i.e. prokaryotes and eukaryotes. It has a major contribution to such diverse processes as photosynthesis, free radical generation, DNA replication, protein synthesis and cell proliferation (1-3).
• Essential for synthesis of heme proteins such as hemoglobin, myoglobin, the cytochrome and several enzymes (peroxidase, catalase). Hemoglobin is the oxygen carrier protein of red blood cells. It also carries carbon dioxide from tissues to the lungs where it exchanges for oxygen.
• Involved in energy production (in the cytochromes and as iron-sulfur clusters bound to some proteins of the electron transport chain) and DNA synthesis. In the latter Fe²⁺ is involved as metal cofactor in a newly identified nuclear protein called pirin (a nonheme protein), a novel highly conserved 32-kDa protein with 290 amino acids (4). Although the exact function of pirin has not been established yet it appears that it has no enzymatic activity but it can bind to a nuclear transcription factor (NFI). This suggests pirin may act as a transcription cofactor. NFI has been shown to stimulate DNA replication and RNA polymerase II-driven transcription (3).
• Involved in enzymatic and nonenzymatic activity of iron-binding nonheme proteins. For instance, transferrin, ferritin and lactoferrin are examples of nonenzymatic nonheme iron-binding proteins. The former two are involved in the transport and storage of iron, respectively while the third exhibits a wide spectrum of antimicrobial and immunotropic properties. Lactoferrin also plays a role in the absorption of nutrients such as the metal ions iron, manganese and zinc as well as sugars (5,6). The nonheme proteins with enzymatic activity such as diiron hydroxylases (AlkB - an omega hydroxylase, soluble methane monooxygenase and toluene monooxygenase) appear to have a ferryl species i.e. [Fe(IV)O]²⁺ involved in the catalytic process. Such a molecular species can be formed under a variety of conditions including those that are characteristic of the Fenton reaction (7). Highly reactive intermediates are likely to be formed during the hydroxylation of an unfunctionalized alkyl group for this kind of substrate is very hard to attack unless it is "softened" by a highly reactive species like the ferryl ion. A typical example of such an oxidation is the hydroxylation of fatty acids in the omega position (8).
• Interactions: Copper, cobalt (as vitamin B12), manganese and vitamin C are necessary for iron absorption. High intake of calcium, magnesium and zinc can interfere with iron absorption. Animal studies showed that iron deficiency can cause altered folate utilization. This relationship is best seen during the reproductive and neonatal life cycle (9). Some antiinflammatory drugs, such as aspirin and ibuprofen may contribute to iron loss through discreet gastrointestinal bleeding. Given the central role played by iron in the cellular metabolism a recent medical hypothesis put forward the idea that excess cellular iron together with low tryptophan, zinc and manganese may have a role in carcinogenesis (10). Thus, besides its ability to catalyze Fenton-type reactions that generate oxygen reactive species excess iron may also interfere with energy production in mitochondria by complexing to citric acid and other Krebs cycle compounds and thus slowing down the reactions in the cycle. In the presence of iron, quinolinate an intermediate in the tryptophan degradation pathway was shown to cause an increase in lipid peroxidation. Excess iron may also interfere with MnSOD activity and the ability of cells to undergo apoptosis.
• Best food sources: Beef and pork liver, heart and kidney, raw clams, red meat, eggs, nuts, beans, molasses, oatmeal.