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MedChem > Iron uptake, distribution and reaction > Flashcards

Iron uptake, distribution and reaction Flashcards

1
Q

What is the definition of Oxidation?

A

the reaction with oxygen

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2
Q

What is oxidation?

A

The addition of oxygen

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3
Q

What is reduction?

A

The loss of oxygen

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4
Q

What is hemochromatosis?

A

excessive absorption of dietary iron and altered iron storage

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5
Q

What are the treatments for hemochromatosis?

A

blood removal, reduced iron intake, avoid high vitamin C

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6
Q

Is heme or noheme food more absorbed?

A

heme

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7
Q

What is a source of heme foods?

A

meat, fish

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8
Q

What is a source of nonheme food?

A

legumes, vegetables etc

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9
Q

What are Rhizobia?

A

a type of bacteria that can fix nitrogen. They infect legumes

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10
Q

What are leghemoglobin?

A

funcitons as an oxygen buffer. Can shift between Ferrous iron and Ferric iron. This mains an oxygen concentration that is low enough to allow nitrogenase to funciton and provide oxygen for the bacteria.

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11
Q

What are some examples of heme proteins?

A

hemoglobin
myoglobin
p450

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12
Q

What are some examples of nonheme proteins?

A

transferrins
ferritin
enzymes that contain iron in their active site

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13
Q

How is iron homeostasis maintained?

A

Digestion, absorption, transport, storage, and excretion

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14
Q

What are some factors that affect iron digestion and absorption?

A
  1. Iron levels
  2. iron status
  3. type of iron in food
  4. amount of stomach acid from digestion
  5. dietary factors that enhance or inhibit absorption
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15
Q

What are the functions of iron in hemoglobin?

A
  1. Carry o2 from the lungs to the rest of the body
  2. Carries CO2 to the lungs
  3. Cofactor for many biological rxns
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16
Q

What are the functions of iron in myoglobin?

A

Carries oxygen to the skeletal and heart muscles

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17
Q

What are the functions of Iron-sulfur clusters?

A

mitochondrial electron transport

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18
Q

20-30 percent of iron in your body is stored as..

A

ferritin and hemosiderin ( iron holding proteins)

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19
Q

What is the main consumer of iron?

A

bone marrow

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20
Q

Where does iron absorption occur?

A

small intestines, duodenum and proximal jejunum w

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21
Q

What causes iron absorption to increase?

A
  1. Stimulation of eyrthropoiesis ( production of RBC). Need large amount of iron to make erythrocytes
  2. Hypoxia
  3. Pregnancy due to the expansion of the erythroid mass and the iron need when developing a fetus
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22
Q

What is hypoxia?

A

A condition where your body or region of your body at a tissues level lacks oxygen

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23
Q

What causes hypoxia?

A

smoking, high altitudes

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24
Q

What pH does heme iron better absorbed at?

A

low pH

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25
Q

What blocks the absorption of iron?

A

antacids, tannins and phytates

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26
Q

What are the factors affecting iron absorption?

A
  1. Type of iron consumed
  2. body iron stores
  3. erythrocytes production rates
  4. type of iron form, heme or nonheme
  5. gender
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27
Q

What is the mechanism for absorption of nonheme?

A
  1. Iron uptake
  2. intraerythrocyte transport
  3. Storage and extraerythrocyte transport
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28
Q

What are some promoters of nonheme iron?

A
  1. Vitamin C
  2. Animal Protein
  3. Sugars
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29
Q

Why does sugars and vitamin increase absorption of non heme iron?

A
  1. Vitamin C forms a soluble chelate with iron

2. Sugar forms a sugar chelate with iron

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30
Q

What are some inhibitors of nonheme iron?

A
  1. Fiber
  2. Oxylate
  3. plant polyphenols
  4. Full body stores of iron
  5. Antacids
  6. H.pylori infection
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31
Q

What are oxylates?

A

Lefty greens like spinach, tofu,chocolate

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32
Q

What are polyphenols?

A

tea, coffee

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33
Q

What are phytates?

A

wheat bread and fibers

34
Q

What are tannins?

A

wine and tea

35
Q

Why do fibers inhibit the absorption of non heme iron?

A

it decreases the transition time in the intestines

36
Q

What generally exist as Fe3+?

A

dietary nonheme

37
Q

What generally exist as Fe2+?

A

dietary heme

38
Q

What is the active form of iron that is transported to erythrocytes?

A

Fe2+

39
Q

How is Fe3+ converted to fe2+?

A

DCYTB

40
Q

Where is the DCYTB located?

A

brush border membrane

41
Q

how is the reduced iron transported into the cell?

A

DMT1 (transporter)

42
Q

What kind of transporter is DMT1?

A

transmembrane proton coupled transporter

43
Q

how is the proton gradient established?

A

sodium hydrogen exchanger on the apical membrane

44
Q

When the demand for iron is low, where is it stored?

A

the ferritin, an intracellular iron storage protein

45
Q

Where are Ferritin’s found?

A

60 percent are found in the liver

46
Q

When the demand for iron is high, how is it transfered across the BLM

A

ferroportin 1

47
Q

What happens to iron when it is transported into the intestinal epithelial cells?

A
  1. Transported into circulation across the basolateral membrane
  2. stored in ferritin and sheds with the intestinal epithelial cells
48
Q

What is ferroportin 1?

A

It is the only know iron exporter

49
Q

What is Transferrin receptors type 1? (TfR1)

A

How iron is regulated. Iron from the plasma can be entered through this receptor for it to be shed and removed from the body

50
Q

How is iron transported out to the body to use?

A
  1. Transverses the BLM via FPN1
  2. Exit is coupled with iron oxidation via HEPH
  3. Ferric ion binds with transferrin in the interstitial fluids to be distributed throughout the body
51
Q

What causes Type IV hemochromatosis?

A

mutation in fpn1

52
Q

What is ferroxidase?

A

an enzyme that catalyzes the oxidation of Fe 2+ –> Fe3+ allowing it to be loaded to transferrin

53
Q

What is HEPH?

A

a membrane bound ferroxidase that catalyzes the oxidation of Fe 2+ –> Fe3+ in the duodenum allowing it to be loaded to transferrin

54
Q

What is ceruloplasmin?

A

a ferroxidase that catalyzes the oxidation of Fe 2+ –> Fe3+ anywhere else in the body allowing it to be loaded to transferrin

55
Q

What is the affinity of transferrin to iron like?

A

Extremely high at physiological pH. Almost all nonheme transferrin circulating is bound to transferrin

56
Q

What are the two main functions of transferrin?

A
  1. Makes the Ferric iron more soluble

2. Reducing irons reactivity

57
Q

Why does transferrin have a high affinity for iron?

A

It is abundant and it has two binding sites for it

58
Q

When does cellular internalization of transferrin+ferric ion occur?

A

Almost immediately under physiological pH. The transferrin receptor 1

59
Q

What transporters can transport free irons?

A
  1. DMT 1
  2. ZIP 8
  3. ZIP 14
    Only transfers soluble irons. So Iron 3+ MUST FIRST be reduced to fe2+
60
Q

What is CD163?

A

It is a macrophage specific protein that specializes to take free hemoglobin and bind it with haptoglobin.

61
Q

What is haptoglobin?

A

binds free hb and inhibit its oxidative property

62
Q

What is hemopexin?

A

A plasma protein with the highest affinity for heme

63
Q

What is low density lipoprotein receptor (LRP1)?

A

it will uptake heme complex that is attached to hemopexin?

64
Q

What is heme responsive gene 1?

A

another protein that can import heme

65
Q

What is SCARA5?

A

Its another pathway for iron uptake. It takes in ferritin which stores iron.

66
Q

What can intracellular iron be stored ass?

A
  1. Ferritin

2. LIP

67
Q

What is Mitoferrin 1 and Mitoferrin 2?

A

Transport the Ferritin into the mitochondria, where it can form FE-S cluster and heme

68
Q

Which form of storage is preferred LIP (Labile iron pool) or Ferritin?

A

Ferritin because LIP is responsible for oxidative stress and can form free radicals

69
Q

What is Hepcidin?

A

It is encoded by HAMP. It is a master regulator of systemic iron metabolism. It binds to the extracellular domain of FPN1. This is induce endocytosis and degradation of this transmembrane protein.

70
Q

What is LIP?

A

A pool of iron complex with low affinity ligands

71
Q

What regulates Hepcidin?

A
  1. Iron stores, iron status
  2. Inflammation IL-6 is the main inducer of hepcidin. Up regulate IL-6=degrade of hepcidin, the body cannot export iron
  3. Regulation by hypoxia or anemia
  4. Regulation by erythroid factors
72
Q

What are IRE?

A

Iron responsive element

73
Q

What is IRP?

A

Iron regulatory protein.

74
Q

What happens when IRP binds to the 3’ end of mRNA?

A

translation and protein synthesis is increased

75
Q

What happens when IRP binds to the 5’ end of mRNA?

A

translation and protein synthesis is stopped

76
Q

What happens when your cell is depleted of iron?

A

It needs more iron so:
IRP binds to the 5’ end IRE of ferritin and FPN1 blocking translation and protein synthesis. Blockage to ferritin translation.
IRP binds that the 3’ end IRE of Transferrin receptor 1 to increase synthesis because you want more iron to come in from the plasma.

77
Q

What happens when your body has a lot of iron?

A

IRP 1 and IRP 2 becomes unavailable to bind to IRE. Want to increase Ferritin and Ferroportin. No need to bring iron into the cell want to store it instead.

78
Q

How is Transferrin Receptor 1 recycled?

A
  1. Clathrin medicated endocytosis
  2. ph drops causing a conformational change in transferrin. The pH causes and causes the affinity for non heme iron to transferrin to be decreased.
  3. Iron 3+ is released
  4. Iron 3+ is oxidized to iron 2 via STEAP3
  5. Transferrin receptor and apotransferrin is recycled back
79
Q

What is Nitric Oxide?

A

It is a free radical that reacts with two things. It is synthesized by Nitric Oxide Synthase

80
Q

What two things are Nitric Oxide reactive with?

A
  1. Iron

2. Another radical species

81
Q

What happens when NO forms with Iron in the LIP?

A

It forms a complex called DNIC. Adding the NO to the iron is basically like taking away the iron. It appears like an iron starved phenotype.

MedChem (2 decks)

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