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HUN 4221 EXAM 3 > IRON > Flashcards

IRON Flashcards

1
Q

What type of metal is Iron?

A

Transition metal

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2
Q

What defines a transition metal?

A

They can assume multiple oxidation states

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3
Q

What does the body use Iron for?

A

For oxidation-reduction reactions and electron transfer

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4
Q

What is the reduced form of iron?

A

Ferrous 2+

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5
Q

What is the oxidized form of iron?

A

Ferric 3+

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6
Q

At what pH will ferrous begin to precipitate out?

A

Around 6-6.5

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7
Q

At what pH will Ferric begin to ppt out?

A

Around 2.5-3

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8
Q

Why is Ferrous more bioavaible than ferric?

A

Because it is more soluble in lower pH levels (when it is absorbed in the small intestine, the pH levels are pretty low and and Ferric ppt out not Ferrous.)

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9
Q

Where is Iron located in the body?

A 
2/3 in hemoglobin & Myoglobin
Heme enzymes
Non heme enzymes
Intracellular labile iron
transferrin
ferritin/hemosiderin
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10
Q

What is the function of Iron in hemoglobin and myoglobin?

A

Binding and transport of Oxygen

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11
Q

What is the function of Heme enzymes?

A

Electron transport

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12
Q

What is the function of non heme enzymes?

A

Oxidative metabolism

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13
Q

What is the function of intracellular labile iron?

A

Gene expression

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14
Q

What is the function of transferrin?

A

Transport

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15
Q

What is the function of Ferritin/Hemosideerin?

A

Storage

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16
Q

How much Iron is found in women and males?

A

2.3 and 3.8

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17
Q

What is hemoglobin?

A

A tetrameric protein and in each of the subunits there is a heme group (heme = an iron locked into the center)

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18
Q

Briefly describe the process of Whole body Iron metabolism

A

Bone Marrow:
-Red blood cells are synthesized there and live for about 120 days in the circulation
Macrophages:
-Red blood cells are then eaten (phagocytosed) by marcrophages and recycle the iron back into the plasma.
Transferrin:
-Iron in the plasma will bind to its transport protein transferrin and most of it will travel back to the bone marrow or some will be stored in the liver.

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19
Q

What is the RDA for reproductive women and of that amount how much is absorbed?

A

18 mg and only 1-2 mg is absorbed in the small intestine.

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20
Q

How much iron is needed daily in the bone marrow?

A

24 mg

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21
Q

What is the only way to get rid of excess iron?

A

By blood loss

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22
Q

What are food sources of iron?

A

Heme iron:
-meat
Non heme:
-plant products

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23
Q

What is heme iron?

A

Fe is contained in a protoporphyrin ring
Found in meat in hemoglobin, myoglobin, and cytochromes
Highly bioavailable

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24
Q

What is non heme iron?

A

Can be organic chelates (e.g. ferric citrate, ferrous fumarate)
Can be constituents of biological molecules (e.g. iron-sulfur enzymes, ferritin)
Found in plants and meat
Relatively poorly bio available

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25
Q

What are nutrients that enhance Iron uptake?

A 
Ascorbic acid (Vit. C) because it is a reducing agent (keeps it in the Ferrous form)
Dietary Protein (Cys, His)
Iron Chelation (e.g. heme)
"Meat factor"
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26
Q

What are Endogenous factors that enhance Iron Uptake?

A

Enhanced erythropoiesis
Low iron stores
Hemochromatosis
HCl (stomach acid) because it keeps Ferrous soluble

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27
Q

What factors inhibit Iron uptake?

A 
Phytic acid
Oxalic acid
Polyphenols (cofee and tea) 
high iron stores
infection/inflammation 
lack of stomach acid
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28
Q

What does DMT1 stand for?

A

Divalent Metal Transporter 1

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29
Q

What is the main function of DMT1?

A

Transport Iron into the intestinal cell (enterocyte)

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30
Q

What is the tissue distribution of DMT1?

A

ubiquotous; abundant in duodenum

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31
Q

Where is DMT1 located?

A

Apical surface of enterocyte

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32
Q

What is the structure of DMT1?

A

Transmembrane protein

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33
Q

How is DMT1 regulated?

A

induced by iron deficiency

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34
Q

What are interesting facts of DMT1?

A

Mutations in DMT1 lead cause anemia

DMT1 first discovered in rodents and with anemia

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35
Q

What is the official gene name for DMT1?

A

Slc11a2

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36
Q

What is Dcytb and does it stand for?

A

A ferrireductase; Duodenal cytochrome B

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37
Q

What is the main function of Dcytb?

A

Reduces Ferric to Ferrous so it can be transported by DMT1

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38
Q

In what tissue is Dcytb distributed in?

A

duodenum, spleen, liver, brain

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39
Q

How is Dcytb regulated?

A

Induced by Iron deficiency

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40
Q

Interesting fact of Dcytb?

A

It uses ascorbate to provide reducing equivalents

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41
Q

What is ferroportin?

A

An iron-export protein

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42
Q

In what tissues is Ferroportin distributed

A

duodenum, spleen, liver, placenta

43
Q

How is ferroportin regulated?

A

Induced by iron deficiency (intenstine) but by iron loading (macrophage)

44
Q

What is the main whole body regulating point of entry of iron into the body?

A

Ferrportin

45
Q

What is essential for iron export?

A

Ferroportin

46
Q

What is hephaestin’s main function?

A

A ferroxidase, it oxidizes Ferrous to Ferric so it can bind to transferrin

47
Q

What is the structure of hephaestin?

A

cystolic protein with single transmembrane domain

48
Q

In what tissues is hephaestin distributed in?

A

Duodenum, lung, kidney,

49
Q

A mutation in hephaestin may lead to what?

A

Anemia

50
Q

How is hephaestin regulated?

A

Induced by iron deficiency (intestine)

51
Q

The bone marrow is the site of what?

A

Erythropoiesis

52
Q

How does the bone marrow get iron?

A

From only transferrin via the transferrin receptor

53
Q

How is iron metabolized in erythroid cell

A
  1. Transferrin receptor TfR1 binds Fe-loaded transferrin (Fe-Tf) at the cell surface
  2. Fe-Tf bound to TfR1 is internalized into endosomes in the cell
  3. Fe3+ is reduced to Fe2+ which is transported into the cyotsol via DMT1
  4. Fe is taken up chiefly by mitochondria for heme synthesis
  5. TfR1-Tf complex recycles back to cell surface
  6. At cell surface, TfR1 releases Tf, which is free to bind more Fe and cycle again.
54
Q

What is eALAS?

A

Erythroid Amino Levulinic Acid synthase

-the rate limiting enzyme in heme biosynthetic pathway

55
Q

Where are macrophages found?

A

In the spleen, the liver and bone marrow

56
Q

What system are macrophages known for?

A

Reticuloendothelial system (res)

57
Q

What is the reticuloendothelial system?

A

Refers to macrohages of the liver, spleen, and bone marrow
Cells of the res ingest old RBCs and recycle their iron
The res also serves as a large storage reservoir for iron

58
Q

What is Ferritin?

A

A large molecule found in cells that stores iron

59
Q

What is the structure of Ferritin?

A

It has a H-ferritin (heavy chain) and L-ferritin (light chain) and has a core with some ferric oxyhydroxide (PO4)

60
Q

Where is iron mainly stored?

A

In the liver

61
Q

In genetic disorders of iron overload, where does iron mainly load?

A

In the hepatocytes of the liver

62
Q

What is the liver’s job in body iron status regulation?

A

It senses body iron status and regulated body iron balance by producing the iron-regulatory hormone, hepcidin

63
Q

In iron overload how is non-transferrin bound iron taken up into the liver?

A

Through Zip14

64
Q

Where is iron balanced maintained?

A

At the point of absorption in the intestine

65
Q

What hormone tells the body to stop absorbing iron?

A

Hepcidin

66
Q

What is hepcidin?

A

A peptide hormone produced by the liver

67
Q

How is Hepcidin induced?

A

By iron

68
Q

How is Hepcidin shut off?

A

Shut off during iron deficiency

69
Q

Where is hepcidin secreted into?

A

The circulation

70
Q

When hepcidin is produced, where does it go and what does it bind to?

A

It goes to the intestine and bind to ferroportin causing it to degrade, so now iron is trapped in the cells.

71
Q

Iron absorption is controlled by…

A

Hepcidin

72
Q

How are serum iron levels controlled?

A

By hepcidin binding to ferroportin on marcopahges causing it degrade

73
Q

Hepcidin inhibits iron release from where?

A

Macrophages and duodenum

74
Q

Slide 59.

A

Common Motif

75
Q

What are the biochemical functions of Iron?

A

Di oxygen transport
Oxidative and reductive transformations
Electron transfer

76
Q

What is an example of oxidative and reductive transformations?

A

Cytochrome P450s

77
Q

What is an example of electron transfer as a biochemical function of iron?

A

Electron transport chain - Cytochrome oxidase (Complex IV)

78
Q

What is Cytochrome oxidase (Complex iv)

A

It catalyzes the final step in the electron transport chain, contains two heme groups and transfers electrons from oxygen to yield water.

79
Q

What are screening methods of iron status?

A

Measuring functional iron in hemoglobin concentration
Measuring the saturation of TIBC/ transferring for tissue iron supply
Measuring serum ferriin in iron stores

80
Q

What is the definitive method of measuring iron status?

A

Tissue biopsy: liver or bone marrow

81
Q

Why is hemoglobin concentration is poor indicator of iron status?

A

Because

  • RBCs have a long-life span (120 d)
  • Low [Hb] levels can be due to many things such as folate/B12 deficiency, acute hemorrhage, and red cell disorders such as sickle cell, thalassemia.
82
Q

Iron deficiency can lead to what?

A

Low Hb levels (anemia)

83
Q

Why is [Hb] the most commonly used method to screen for iron deficiency?

A

Because it is fast, cheap, and easy to do.

84
Q

When measuring Transferrin saturation what happens in iron def. and iron overload?

A

Def- low serum Fe and High TIBC/ferritin

Overload- high serum Fe and normal or ow TIBC/ferritin

85
Q

What is the main disadvantage of measuring tansferrin saturation for clinical assessment?

A

Serum iron shows a pronounced diurnal variation

86
Q

Plasma ferritin levels correlate strongly with what?

A

Tissue nonheme iron levels (storage iron)

87
Q

Low plasma ferritin means what?

A

Iron def

88
Q

High plasma ferritin means what?

A
  1. iron overload

2. inflammation, infection, chronic disease

89
Q

Study slide 74

A

.

90
Q

What is the single most nutrient deficiency in the world?

A

Iron

91
Q

Causes of iron def

A

Blood loss - menstruation, gastrointestinal tract (food sensitivity, hookworms), genitourinary tract, respiratory tract, blood donation,
growth
prganancy
inadequate iron absorption- diet low in bioavaiable iron, impaired absrption due to intestinal malabsorpion, gastric surgery, hypochloryhydria, chrons

92
Q

What is stage 1 Iron def?

A

Once iron stores are gone

93
Q

What is stage 2 iron def?

A

Once your body cannot send enough iron to the bone marrow

94
Q

Normal Functioning starts to decline before in iron deficiency even before what is evident?

A

Anemia

95
Q

Consequences of iron def

A 
Poor cognitive performance
Diminished immune function
reduced exercise ad endurance capacity 
anemia
gowth retardation in children 
poor pregnancy outcomes
96
Q

Study slide 84

A

.

97
Q

Most iron overload is due to what>?

A

Herditary hemochromatosis (HH)

98
Q

What is hereditary hemochromatosis?

A

Results from single point mutation C282Y in a gene called HFE which was identified in 1996

99
Q

Where is HH more prevvelant?

A

In northern European descent

100
Q

Clinical signs of HH begin to happen when…

A

40-60 yo and 20-40 g of excess iron has accumulated

101
Q

Common feature of HH are

A 
Lethargy
abdomincal pain
hepatic tenderness
hepatomegaly
arthropathy
hepatocellular carcinoma 
diabetes melitus 
weight loss
hypogonadism
increased skin pigmentation (bronze color)
102
Q

HH results from a decrease of what hormone?

A

Hepcidin

103
Q

Cellular iron metabolism is regulated by

A

IRE/IRP interactions

104
Q

What is the RDA for males and females?

A

8;18mg/day

HUN 4221 EXAM 3 (9 decks)

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