Iron Uptake Flashcards
How does iron act as a nutrient?
It helps carry O2 in blood as hemoglobin
How much dietary iron is absorbed?
10%
What is transferrin?
An iron carrier protein that binds to transferrin receptors on hepatocytes to bring iron into the liver
What is Fe stored as?
Ferritin and hemosiderin
Where are RBCs synthesized?
In bone marrow
What is the responsibility of the spleen in the iron cycle?
RBC recycling
Is the site of iron homeostasis
What does hepcidin do?
Inhibits Fe transport by inhibitory export
Which cellular processes is iron essential for?
TCA cycle
ETC
Coenzyme for DNA replication machinery
O2 transfer as heme
Why do bacteria need iron from the host?
They much acquire iron from the host to replicate and cause diease
Which forms can iron exist in the body?
Reduced ferrous form (Fe2+) or oxidized ferric form (Fe3+)
Why is good and bad about the redox potential of iron?
Good = versatile
bad = very reactive
What is ROS?
Reactive oxygen species which are very damaging to macromolecules, especially DNA
Why is free [iron] not high in cells?
To prevent reactions that produce ROS
Why is iron limiting?
Lactoferrin, transferrin, ferritin, and hemoglobin bind most available iron
What does lactoferrin do?
Ushers Fe3+ to cells
What do neutrophils produce and why?
Neutrophil gelatinase dissociated lipocalin = chelate siderophores
What happens when RBCs are recycled?
Hemopexin binds to lysed Hb
Macrophages pump Fe out of the what?
Phagocytic organelles via the NRAMP1 pump
What are 2 host strategies for hiding iron away from bacteria?
Sequestering it - bind Fe to heme, ferritin, transferrin
Express iron proteins in response to infection
What does hepcidin do?
Decrease blood iron = anemia
Released in response to pro-inflammatory cytokines
What is the most significant form of nutritional immunity?
Sequestration of iron
What is the majority of eukaryotic Fe found?
Intracellularly, sequestered as ferritin and complexed as heme
What are the characteristics of extracellular Fe?
Insoluble
Neutral pH of serum so Fe is difficult to access
Bound to Fe-associated proteins like transferrin
What do bacteria have receptors for?
Iron-carrying proteins
What are two ways that the nutritional immunity of the host can be overcome?
Siderophores = iron chelators with a very high affinity for Fe3+ and are very chemically diverse
Receptor-mediated iron acquisition from host proteins = the uptake of heme or other iron-containing proteins
What is the main difference between siderophores and iron-containing molecules?
Siderophores can be taken up by the bacteria while iron-containing molecules must be stripped of iron
How do gram-positive bacteria sequester iron?
Heme can be brought in directly
Siderophores are brought in as a complex
Iron-containing proteins are stripped of Fe + transported via ABC transporter (specificity)
How do gram-negative bacteria sequester iron?
There are transferrin (secreted scavenge binding), siderophore, and heme receptors on the outer membrane (doesn’t need to be all)
The iron is stripped prior to entry into the cell and iron gets handed off to the periplasmic proteins prior to transport into the cell
What disease does B. burgdorferi cause and what is the structure like?
Lyme
Has an outer membrane and inner membrane with a thin layer of peptidoglycan in between (spirochetes)
What is unique about B. burgdorferi?
It can live without iron as it has eliminated genes that require iron and substituted the need for iron for manganese
What are siderophores?
Small high affinity iron-chelating compounds that are secreted by microbes and fungi and have a ton of diversity reflective of evolutionary arms race
How do mammals respond to siderophores?
Siderocalin, a lipocalin-type protein, binds siderophores of bacteria to prevent pathogens from accessing iron
How do bacteria respond to siderocalin?
Novel siderophore synthesis
Glycosylating existing siderophores
How can E. coli acquire pathogenicity?
The acquisition of plasmids
Describe the UPEC infection cycle
- Type I fimbrae binds mannose on glycosylated urinary tract epithelial cells
- Rho-GTPase mediated signaling causes actin reorganization = promotes phagocytosis
3a. Replication in phagosome + exocytosis = slow
3b. Vesicle destruction by the bacteria allows intracellular respiration = fast
3c. Some vesicles do not lyse but get encased in actin = quiescent intracellular reservoirs
- Release of pathogens once pathogen gains access to host nutrients after 3b
What does alpha-hemolysin do and at what step of the UPEC infection cycle is it released?
Lyse host cells and liberate iron
3b
What can cranberries do to UPEC?
Bind to UPEC which blocks binding to the epithelial cells
What happens to UPEC infections if you eat tums?
Decreases the acidity of the urine which may decrease infection
