Got Iron?

The Silent Battle

What about iron?

O2

O2O2

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.

• Clinical manifestations:– Local toxicity= abdominal pain,

vomiting, diarrhea, GI bleeding

– Systemic toxicity= injury to the cardiovascular system and liver

• Metabolic acidosis

Looks like candy, but can be harmful

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

ChelatorGreek word = “claw”

•Biochemical engineers have used bacterial siderophores to help design treatments for patients with iron loading.

What about other metals?

copper role in making neurotransmitters, elasticityof 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

Name Function

Nutritional Recommendations

AgeMales(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