Iron Uptake

Question 1

How does iron act as a nutrient?

Answer 1

It helps carry O2 in blood as hemoglobin

Question 2

How much dietary iron is absorbed?

Answer 2

10%

Question 3

What is transferrin?

Answer 3

An iron carrier protein that binds to transferrin receptors on hepatocytes to bring iron into the liver

Question 4

What is Fe stored as?

Answer 4

Ferritin and hemosiderin

Question 5

Where are RBCs synthesized?

Answer 5

In bone marrow

Question 6

What is the responsibility of the spleen in the iron cycle?

Answer 6

RBC recycling
Is the site of iron homeostasis

Question 7

What does hepcidin do?

Answer 7

Inhibits Fe transport by inhibitory export

Question 8

Which cellular processes is iron essential for?

Answer 8

TCA cycle
ETC
Coenzyme for DNA replication machinery
O2 transfer as heme

Question 9

Why do bacteria need iron from the host?

Answer 9

They much acquire iron from the host to replicate and cause diease

Question 10

Which forms can iron exist in the body?

Answer 10

Reduced ferrous form (Fe2+) or oxidized ferric form (Fe3+)

Question 11

Why is good and bad about the redox potential of iron?

Answer 11

Good = versatile
bad = very reactive

Question 12

What is ROS?

Answer 12

Reactive oxygen species which are very damaging to macromolecules, especially DNA

Question 13

Why is free [iron] not high in cells?

Answer 13

To prevent reactions that produce ROS

Question 14

Why is iron limiting?

Answer 14

Lactoferrin, transferrin, ferritin, and hemoglobin bind most available iron

Question 15

What does lactoferrin do?

Answer 15

Ushers Fe3+ to cells

Question 16

What do neutrophils produce and why?

Answer 16

Neutrophil gelatinase dissociated lipocalin = chelate siderophores

Question 17

What happens when RBCs are recycled?

Answer 17

Hemopexin binds to lysed Hb

Question 18

Macrophages pump Fe out of the what?

Answer 18

Phagocytic organelles via the NRAMP1 pump

Question 19

What are 2 host strategies for hiding iron away from bacteria?

Answer 19

Sequestering it - bind Fe to heme, ferritin, transferrin

Express iron proteins in response to infection

Question 20

What does hepcidin do?

Answer 20

Decrease blood iron = anemia
Released in response to pro-inflammatory cytokines

Question 21

What is the most significant form of nutritional immunity?

Answer 21

Sequestration of iron

Question 22

What is the majority of eukaryotic Fe found?

Answer 22

Intracellularly, sequestered as ferritin and complexed as heme

Question 23

What are the characteristics of extracellular Fe?

Answer 23

Insoluble
Neutral pH of serum so Fe is difficult to access
Bound to Fe-associated proteins like transferrin

Question 24

What do bacteria have receptors for?

Answer 24

Iron-carrying proteins

Question 25

What are two ways that the nutritional immunity of the host can be overcome?

Answer 25

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

Question 26

What is the main difference between siderophores and iron-containing molecules?

Answer 26

Siderophores can be taken up by the bacteria while iron-containing molecules must be stripped of iron

Question 27

How do gram-positive bacteria sequester iron?

Answer 27

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)

Question 28

How do gram-negative bacteria sequester iron?

Answer 28

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

Question 29

What disease does B. burgdorferi cause and what is the structure like?

Answer 29

Lyme
Has an outer membrane and inner membrane with a thin layer of peptidoglycan in between (spirochetes)

Question 30

What is unique about B. burgdorferi?

Answer 30

It can live without iron as it has eliminated genes that require iron and substituted the need for iron for manganese

Question 31

What are siderophores?

Answer 31

Small high affinity iron-chelating compounds that are secreted by microbes and fungi and have a ton of diversity reflective of evolutionary arms race

Question 32

How do mammals respond to siderophores?

Answer 32

Siderocalin, a lipocalin-type protein, binds siderophores of bacteria to prevent pathogens from accessing iron

Question 33

How do bacteria respond to siderocalin?

Answer 33

Novel siderophore synthesis
Glycosylating existing siderophores

Question 34

How can E. coli acquire pathogenicity?

Answer 34

The acquisition of plasmids

Question 35

Describe the UPEC infection cycle

Answer 35

1. Type I fimbrae binds mannose on glycosylated urinary tract epithelial cells
2. 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

4. Release of pathogens once pathogen gains access to host nutrients after 3b

Question 36

What does alpha-hemolysin do and at what step of the UPEC infection cycle is it released?

Answer 36

Lyse host cells and liberate iron
3b

Question 37

What can cranberries do to UPEC?

Answer 37

Bind to UPEC which blocks binding to the epithelial cells

Question 38

What happens to UPEC infections if you eat tums?

Answer 38

Decreases the acidity of the urine which may decrease infection