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HUN 4221 EXAM 3 > IRON > Flashcards

IRON Flashcards

(104 cards)

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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
What are nutrients that enhance Iron uptake?
``` 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" ```
26
What are Endogenous factors that enhance Iron Uptake?
Enhanced erythropoiesis Low iron stores Hemochromatosis HCl (stomach acid) because it keeps Ferrous soluble
27
What factors inhibit Iron uptake?
``` Phytic acid Oxalic acid Polyphenols (cofee and tea) high iron stores infection/inflammation lack of stomach acid ```
28
What does DMT1 stand for?
Divalent Metal Transporter 1
29
What is the main function of DMT1?
Transport Iron into the intestinal cell (enterocyte)
30
What is the tissue distribution of DMT1?
ubiquotous; abundant in duodenum
31
Where is DMT1 located?
Apical surface of enterocyte
32
What is the structure of DMT1?
Transmembrane protein
33
How is DMT1 regulated?
induced by iron deficiency
34
What are interesting facts of DMT1?
Mutations in DMT1 lead cause anemia | DMT1 first discovered in rodents and with anemia
35
What is the official gene name for DMT1?
Slc11a2
36
What is Dcytb and does it stand for?
A ferrireductase; Duodenal cytochrome B
37
What is the main function of Dcytb?
Reduces Ferric to Ferrous so it can be transported by DMT1
38
In what tissue is Dcytb distributed in?
duodenum, spleen, liver, brain
39
How is Dcytb regulated?
Induced by Iron deficiency
40
Interesting fact of Dcytb?
It uses ascorbate to provide reducing equivalents
41
What is ferroportin?
An iron-export protein
42
In what tissues is Ferroportin distributed
duodenum, spleen, liver, placenta
43
How is ferroportin regulated?
Induced by iron deficiency (intenstine) but by iron loading (macrophage)
44
What is the main whole body regulating point of entry of iron into the body?
Ferrportin
45
What is essential for iron export?
Ferroportin
46
What is hephaestin's main function?
A ferroxidase, it oxidizes Ferrous to Ferric so it can bind to transferrin
47
What is the structure of hephaestin?
cystolic protein with single transmembrane domain
48
In what tissues is hephaestin distributed in?
Duodenum, lung, kidney,
49
A mutation in hephaestin may lead to what?
Anemia
50
How is hephaestin regulated?
Induced by iron deficiency (intestine)
51
The bone marrow is the site of what?
Erythropoiesis
52
How does the bone marrow get iron?
From only transferrin via the transferrin receptor
53
How is iron metabolized in erythroid cell
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
What is eALAS?
Erythroid Amino Levulinic Acid synthase | -the rate limiting enzyme in heme biosynthetic pathway
55
Where are macrophages found?
In the spleen, the liver and bone marrow
56
What system are macrophages known for?
Reticuloendothelial system (res)
57
What is the reticuloendothelial system?
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
What is Ferritin?
A large molecule found in cells that stores iron
59
What is the structure of Ferritin?
It has a H-ferritin (heavy chain) and L-ferritin (light chain) and has a core with some ferric oxyhydroxide (PO4)
60
Where is iron mainly stored?
In the liver
61
In genetic disorders of iron overload, where does iron mainly load?
In the hepatocytes of the liver
62
What is the liver's job in body iron status regulation?
It senses body iron status and regulated body iron balance by producing the iron-regulatory hormone, hepcidin
63
In iron overload how is non-transferrin bound iron taken up into the liver?
Through Zip14
64
Where is iron balanced maintained?
At the point of absorption in the intestine
65
What hormone tells the body to stop absorbing iron?
Hepcidin
66
What is hepcidin?
A peptide hormone produced by the liver
67
How is Hepcidin induced?
By iron
68
How is Hepcidin shut off?
Shut off during iron deficiency
69
Where is hepcidin secreted into?
The circulation
70
When hepcidin is produced, where does it go and what does it bind to?
It goes to the intestine and bind to ferroportin causing it to degrade, so now iron is trapped in the cells.
71
Iron absorption is controlled by...
Hepcidin
72
How are serum iron levels controlled?
By hepcidin binding to ferroportin on marcopahges causing it degrade
73
Hepcidin inhibits iron release from where?
Macrophages and duodenum
74
Slide 59.
Common Motif
75
What are the biochemical functions of Iron?
Di oxygen transport Oxidative and reductive transformations Electron transfer
76
What is an example of oxidative and reductive transformations?
Cytochrome P450s
77
What is an example of electron transfer as a biochemical function of iron?
Electron transport chain - Cytochrome oxidase (Complex IV)
78
What is Cytochrome oxidase (Complex iv)
It catalyzes the final step in the electron transport chain, contains two heme groups and transfers electrons from oxygen to yield water.
79
What are screening methods of iron status?
Measuring functional iron in hemoglobin concentration Measuring the saturation of TIBC/ transferring for tissue iron supply Measuring serum ferriin in iron stores
80
What is the definitive method of measuring iron status?
Tissue biopsy: liver or bone marrow
81
Why is hemoglobin concentration is poor indicator of iron status?
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
Iron deficiency can lead to what?
Low Hb levels (anemia)
83
Why is [Hb] the most commonly used method to screen for iron deficiency?
Because it is fast, cheap, and easy to do.
84
When measuring Transferrin saturation what happens in iron def. and iron overload?
Def- low serum Fe and High TIBC/ferritin | Overload- high serum Fe and normal or ow TIBC/ferritin
85
What is the main disadvantage of measuring tansferrin saturation for clinical assessment?
Serum iron shows a pronounced diurnal variation
86
Plasma ferritin levels correlate strongly with what?
Tissue nonheme iron levels (storage iron)
87
Low plasma ferritin means what?
Iron def
88
High plasma ferritin means what?
1. iron overload | 2. inflammation, infection, chronic disease
89
Study slide 74
.
90
What is the single most nutrient deficiency in the world?
Iron
91
Causes of iron def
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
What is stage 1 Iron def?
Once iron stores are gone
93
What is stage 2 iron def?
Once your body cannot send enough iron to the bone marrow
94
Normal Functioning starts to decline before in iron deficiency even before what is evident?
Anemia
95
Consequences of iron def
``` Poor cognitive performance Diminished immune function reduced exercise ad endurance capacity anemia gowth retardation in children poor pregnancy outcomes ```
96
Study slide 84
.
97
Most iron overload is due to what>?
Herditary hemochromatosis (HH)
98
What is hereditary hemochromatosis?
Results from single point mutation C282Y in a gene called HFE which was identified in 1996
99
Where is HH more prevvelant?
In northern European descent
100
Clinical signs of HH begin to happen when...
40-60 yo and 20-40 g of excess iron has accumulated
101
Common feature of HH are
``` Lethargy abdomincal pain hepatic tenderness hepatomegaly arthropathy hepatocellular carcinoma diabetes melitus weight loss hypogonadism increased skin pigmentation (bronze color) ```
102
HH results from a decrease of what hormone?
Hepcidin
103
Cellular iron metabolism is regulated by
IRE/IRP interactions
104
What is the RDA for males and females?
8;18mg/day

HUN 4221 EXAM 3 (9 decks)

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