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Got Iron? The Silent Battle What about iron? O2 O2 O2 O2 Too little and too much! • Deficiency – cellular = cell death – systemic = anemia • Excess – generation of free radicals (damage to nucleic acids, proteins, lipid membranes) Hemochromatosis Acute Iron Poisoning • Iron overdose is one of the leading causes of fatality from toxicological agents in children less than 6 years of age. Looks like candy, but can be harmful • Clinical manifestations: – Local toxicity= abdominal pain, vomiting, diarrhea, GI bleeding – Systemic toxicity= injury to the cardiovascular system and liver • Metabolic acidosis Death results usually from shock or liver failure Are we the only ones that need iron? Why do microorganisms need iron? • Cellular Respiration • Electron transport – These processes result in the formation of ATP for energy Friends or Foes? • 99.9% of all bacteria do not cause disease • Less than 1% are pathogenic and have mechanisms to overcome the host • Most of these systems involve iron acquisition Pathogens that readily acquire iron multiply rapidly • Pathogen = a microorganism that causes disease – Bacteria – Parasite – Viruses (hijack cell machinery) • Mycobacteria • Salmonella • Neisseria – (gonorrheoa) – (meningitidis) • Staphylococcus • E. coli • Yersinia Our innate immune system response to pathogens Skin and mucosa • 1st line of defense: – Protective barrier • Mucous membrane produces substances that fight microbes Immune cells • Eat up the invader – Macrophages – Neutrophils – Dendritic cells • Produce proteins for defense “The Iron Tug of War” Fe Host vs. Invader (additional strategies ) YOU: made by your liver • Transferrin • Ferritin • Lipocalin – siderocalin Bacteria and parasites • Siderophores: • Proteins that bind iron very tightly – – – – Enterobactin Salmochelin Mycobactin yersinabactin The fight goes on! The host steals iron back from the invader Host Invader Chelator Greek word = “claw” •Biochemical engineers have used bacterial siderophores to help design treatments for patients with iron loading. What about other metals? Name Function copper role in making neurotransmitters, elasticity of blood vessels, important role in collagen formation, healthy immune system chromium Involved in the functioning of skeletal muscle. manganese Antioxidant properties; Fertility; Formation of strong healthy bones, nerves, and muscles; zinc Needed for: Functioning of many (over 200) enzymes; Strong immune system Nutritional Recommendations Age Males (mg/day) Females (mg/day) Pregnancy (mg/day) 7 to 12 months 11 11 N/A 1 to 3 years 7 7 N/A 4 to 8 years 10 10 N/A 9 to 13 years 8 8 N/A 14 to 18 years 11 15 27 19 to 50 years 8 18 27 51+ years 8 8 N/A