title: The possible crucial role of iron accumulation combined with low tryptophan, zinc and manganese in carcinogenesis.
abstract: Iron can react with citric acid, interfering with the Krebs cycle, hence with oxidative phosphorylation. Free iron (Fe) can cause considerable oxidative damage both through Fenton reactions and by activating xanthine oxidase, which produces both superoxide (O(2-)) and uric acid (abundant in many cancers). It can also react with lactic acid, reducing its elimination and increasing the acidity of the cytoplasm. Fe can also wreak havoc by reacting with tryptophan, the least abundant and most delicate essential amino acid, which is necessary for the production of serotonin and other substances required by the immune system to fight cancer. On the other hand, in the presence of iron, the tryptophan metabolite quinolinate causes intense lipid peroxidation. Similarly, several other carcinogenic metabolites of tryptophan are particularly dangerous in the presence of Fe. Excess Fe may also interfere with manganese superoxide dismutase and impair the initiation of apoptosis by the mitochondrion, rendering the cells impervious to all the signals to undergo apoptosis from without and from within the cell. Moreover, Fe may also play a crucial role on telomere repair, by activating telomerase. Therefore, by inhibiting apoptosis and enhancing chromosome repair, Fe may bestow immortality upon the cancer cell. Furthermore, Fe is one of the triggers for mitosis. Therefore, increased Fe levels may be essential for the rapid growth characteristic of many malignancies. In turn, the rapid growth further depletes resources from the healthy tissues, exacerbating the deficiencies of the other elements and reducing the ability to fight the malignancy.
authors.forename: S
authors.initials: S
authors.lastname: Johnson
mesh_terms: D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008345:Manganese / Q000172:deficiency*; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D014364:Tryptophan / Q000172:deficiency*; D015032:Zinc / Q000172:deficiency*
chemical_list: D008345:Manganese; D014364:Tryptophan; D007501:Iron; D013482:Superoxide Dismutase; D019098:Telomerase; D015032:Zinc