Transcript Got Iron? - University of California, Los Angeles

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