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NHM 561 > Iron Part I > Flashcards

Iron Part I Flashcards

1
Q

How much iron does the human body contain?

A

~2-4 grams of iron

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2
Q

Ferrous Form

A

Fe2+

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3
Q

Ferric Form

A

Fe3+

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4
Q

(TRUE/FALSE)

Men have 3x more iron stores compared to females.

A

TRUE

Due to an increased body mass, which is a result of having increased blood; therefore, more hemoglobin AND slightly more muscle mass, so more myoglobin

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5
Q

Iron easily changes between which two forms, thus serving as a catalyst in redox reactions by donating and accepting electrons.

A

Ferric and Ferrous

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6
Q

(TRUE/FALSE)

Free iron is extremely reactive, so it is always associated with a “chaperone.”

A

TRUE

Iron can react as a pro-oxidant if it is not bound up to proteins. It is very important that iron is not circulating as a free form, rather it is bound to a chaperone protein.

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7
Q

**What is the distribution of iron in the body?

A

**
75% as FUNCTIONAL IRON - - most is in the form on heme proteins
a. Hb (65%)
b. Myoglobin (10%)
c. Several enzymes (1-3%) (some iron in the body is used as a coE)

Transported as TRANSFERRIN
Stored as FERRITIN and HEMOSIDERIN

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8
Q

Explain the chemical structure of heme.

A

Iron sits inside the PORPHYRIN RING, which protects the iron from being able to react with other compounds, causing the pro-oxidant and oxidative stress reactions.

It’s unique in that is can easily load and unload oxygen

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9
Q

How is iron transported in the body?

A

TRANSFERRIN (transport protein)

–Transports FERRIC (oxidized iron) in the blood and delivers iron to tissues

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10
Q

How is iron stored in the body?

A

Ferritin and Hemosiderin

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11
Q

What are the two forms of iron found in foods?

A
  1. Heme iron
  2. Non-heme iron
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12
Q

Heme iron

A

Derived from Hb and myoglobin, so only found in meat, fish, poultry

–About 50-60% of the iron in meat, fish, and poultry is heme iron, and the rest is non-heme iron**

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13
Q

Non-Heme iron

A

Found primarily in plant foods (nuts, vegetables, fruits, grains) and fortified foods

–consists primarily of iron salts

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14
Q

Is heme or non-heme iron better absorbed?

A

HEME iron is better absorbed

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15
Q

Is heme or non-heme iron better absorbed?

A

HEME iron is better absorbed

Remember: only 50-60% of the iron in meat, fish, and poultry is heme iron and the rest is non-heme iron**

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16
Q

What is the main way that we lose iron?

A
  1. BLOOD loss
  2. Through sloughing off enterocytes from our digestive track
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17
Q

(TRUE/FALSE)

Iron metabolism is unusual in that iron absorption from the GI tract is the primary regulatory mechanism of iron balance.

A

TRUE

We ABSORB more iron when our bodies are in a deficient state. When iron stores are depleted, the body is facing iron deficiency, absorption will greatly INCREASE.

We will be able to absorb non-heme iron as high as 50%.

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18
Q

The % of iron absorbed depends on what?

A
  1. the type of food consumed, and
  2. the body’s physiological need for iron
  3. gender
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19
Q

(TRUE/FALSE)

There are significant differences in absorption potential between genders.

A

TRUE

Men: absorb 6% of dietary intake
Women: absorb 13% of dietary intake

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20
Q

What happens with iron during pregnancy?

A

During pregnancy, the blood volume will double, as there is a need to supply the developing fetus with oxygen, this will deplete iron stores throughout the gestational period. So, iron absorption will steadily increase, and become more efficient to meet this demand.

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21
Q

(TRUE/FALSE)

Iron balance is controlled at the point of absorption.

A

TRUE. Individuals with low iron stores or iron deficiency absorb a greater fraction of non-heme iron.

In severe iron deficiency anemia, non-heme iron absorption is as high as 50%.

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22
Q

Compared to men, women and children have XXXX iron stores, and absorb a XXXXX % of iron.

A

LOWER

GREATER

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23
Q

Absorption of non-heme iron ranges from XXX to XXX?

A

~2-20%

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24
Q

Absorption of heme iron is XXX%?

A

20%

Absorbed much better

Although heme iron accounts for a smaller proportion of iron in the diet than non-heme iron, it is absorbed 2-3x more readily, and is much less affected by other dietary constitutents.

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25
Q

Explain the absorption of HEME iron.

A

STOMACH: Animal protein reaches the stomach. Hb and myoglobin will be acted on by HCl acid and PROTEASES. The globulin protein will be cleaved off, leaving just the heme portion.

SI: Heme will be directly absorbed into the enterocyte via HCP1 (heme carrier protein 1).

ENTEROCYTE: HEME OXYGENASE breaks down heme, so that iron (FERRIC IRON) is released in the free form. It can bind and be processed where it can exit the enterocyte.

BLOOD: Exits via FERROPORTIN

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26
Q

Explain the absorption of NON-HEME iron.

A

OPTION 1:

STOMACH: Plant protein reaches the stomach; it will be broken down by HCl acid & PROTEASES, breaking off the food components.

SI: What is left is FERROUS iron (Fe2+), which will bind and be brought into the enterocyte, to the DMT1 (Divalent Metal Transporter 1), which sits on the brush border membrane of the enterocyte.

ENTEROCYTE: Fe2+ binds to a LIGAND and will be carried on through the enterocyte, where it is going exit via FERROPORTIN.

OPTION 2: Some of the non-heme iron will be converted to the more oxidized form, FERRIC IRON (Fe3+), which has a couple of options.

  1. Bind to a LIGAND, which helps it maintain some solubility, then it binds to INTEGRIN (type of receptor that bring it into the enterocyte).
  2. Fe3+ can be acted on by Dcytb (Duodenal Cytochrome B Reductase) enzyme, which sits away from the brush border membrane, and is more of a soluble-type enzyme. This acts to reduce iron back to it’s reduced state (FERROUS), so now it can bind to the DMT1 carrier & follow the same pathway.
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27
Q

Heme oxygenase

A

Enzyme in the enterocyte, that breaks down heme so iron is released

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28
Q

Ferroportin

A

Transports Fe2+ out of the enterocyte, as hephaestin oxidizes it so it can attach to transferrin for transport in the blood

29
Q

DMT1

A

Divalent Metal Transporter 1, sits on the brush border membrane on the enterocyte, and will absorb Fe2+

30
Q

Ligand

A

What iron binds to in the enterocyte; provides some solubility

31
Q

Integrin

A

A type of receptor that can bring Fe2+ (Ferric) into the enterocyte

32
Q

Reductase Enzyme

A

Enzyme that reduces iron back to its reduced state (FERROUS), in the enterocyte

33
Q

Dcytb

A

Duodenal Cytochrome B Reductase enzyme; sits AWAY from the brush border membrane, as it is more of a soluble-type enzyme. This enzyme reduces iron back to its reduced state (FERROUS), so now it is able to bind DMT1 carrier and follow the same pathway

34
Q

Hephaestin

A

Copper containing protein; oxidizes iron to FERRIC form as it is transported out of the cell by FERROPORTIN

This oxidation of iron, allows it to bind to transferrin in the blood

35
Q

Once we have iron in the enterocyte, how does it move across the basolateral membrane and into the blood flow? (Hint- there are 3 options).

A

OPTION 1: FERROPORTIN binds the FERROUS iron and HEPHAESTIN will oxidize iron to FERRIC form before iron can bind to the TRANSFERRIN transport protein.

OPTION 2: It can be stored within the enterocyte and used later

OPTION 3: It can be stored within the enterocyte and NOT used later. If the body does not need any additional iron, these cells turnover every 4-5 days. So a good way that body gets rid of iron that it doesn’t need, is through being sloughed off and carried out into the feces.

36
Q

Explain another mechanism in which we regulate iron absorption, that occurs at the basolateral membrane.

A

Remember, how we talked about FERROPORTIN and how it transports iron out of the enterocyte? Well, there is another protein, called HEPCIDIN.

HEPCIDIN is secreted from the liver when the iron stores in the body are starting to get too high. So, the level of iron needs to be tightly controlled, so HEPCIDIN is a hormone that will come to the enterocytes and bind FERROPORTIN and block it from being able to export any iron further. So, eventually, it will be sloughed off when the cells die every 4-5 days and are excreted.

37
Q

(TRUE/FALSE)

Heme must be hydrolyzed from the globin portion of hemoglobin or myoglobin.

A

TRUE

38
Q

HCP1

A

Heme Carrier Protein 1

39
Q

(TRUE/FALSE)

Heme is soluble and is readily absorbed INTACT into the enterocyte via XXXX?

A

TRUE

via HCP1 (heme carrier protein 1)

40
Q

Within the enterocyte, what hydrolyzes the porphyrin ring to release FERROUS iron?

A

HEME OXYGENASE

41
Q

Ferric Hydroxide

A

Fe(OH)3

In the intestine, ferric iron may complex to produce ferric hydroxide, because of the alkaline nature of the intestine.

INSOLUBLE, Not absorbed well

42
Q

Which form of iron is absorbed better?

A

FERROUS iron is absorbed better than FERRIC iron.

43
Q

Ferritin

A

A protein that serves as a shell for iron storage and also serves as a FERRIOXIDASE to convert ferrous iron to FERRIC state for deposition and storage

Short-term storage form

44
Q

Transferrin

A

Transport FERRIC iron in the blood, delivering it to tissues

The iron supply is reflected by the iron saturation of transferrin. (Low saturation indicates an under-supply or deficiency).

A glycoprotein made primarily in the liver

45
Q

(TRUE/FALSE)

The number of transferrin receptors on the cell surfaces is highly regulated.

A

TRUE

When cells are in iron-rich environment, the number of receptors decreases.

When iron supply to the cells is inadequate due to iron deficiency or increased iron demand related to high call turnover, the number of transferrin receptors increases.

46
Q

Hepcidin

A

A protein that functions as the main regulator of iron absorption

It is released from the liver when body iron stores are adequate or high.

Binds to ferroportin on enterocytes, resulting in internalization and degradation of both hepcidin and ferroportin.

With less ferroportin, less iron will get into blood from SI

47
Q

What are some factors that ENHANCE non-heme iron absorption?

A
  1. Gastric acid secretion
  2. ACIDS which acts as a reducing agent to reduce ferric into ferrous form (ascorbic acid, citric acid, lactic acid, tartaric acid)
  3. SUGARS
  4. Meat, poultry, fish (MFP Factor; AAs may improve solubility, promoting absorption).
48
Q

(TRUE/FALSE)

The more oxidized the iron, the most difficult it is for us to absorb it.

A

TRUE

Ferrous is better absorbed than FERRIC

49
Q

What are some factors that INHIBIT iron absorption?

A
  1. Polyphenols in coffee/tea (reduce by 60%)
  2. Phytates and oxalates (bind iron, forming insoluble complexes)
  3. Ca2+ & Phosphorus (by forming complex with iron)
  4. Zinc, Manganese, Nickel compete for absorption via DMT1
50
Q

Why does vitamin C help with iron absorption?

A

Vitamin C can REDUCE FERRIC to FERROUS state, which again, is more easily absorbed

51
Q

Where is iron stored?

A

Liver
Bone Marrow
Spleen

52
Q

What is the primary storage protein of iron in cells?

A

FERRITIN

53
Q

What are the two storage proteins of iron in cells?

A

FERRITIN (primary)

HEMOSIDERIN (more long-term storage)

54
Q

How many iron atoms can be stored in ferritin?

A

~4,500 iron atoms

55
Q

(TRUE/FALSE)

Iron bound to hemosiderin is more readily mobilized than iron bound to ferritin.

A

FALSE

It’s the other way around

Ferritin is more readily mobilized

56
Q

Ferritin consists of how many subunits?

A

24 subunits

57
Q

When infants are born, how much-stored iron do they have?

A

About 6 months worth (then supplementation will be needed)

58
Q

When premature infants are born, how much-stored iron do they have?

A

About 2-3 months, because they were born early, they have much less iron storage and an increased rate of growth than normal full-term infants; so their iron stores are depleted much soon.

They often require increased supplementation

59
Q

In infants, up to XXXX years of age, substantial iron stores are difficult to accumulate when iron intake is adequate due to increased iron requirement related to rapid growth.

A

2 years.

After 2 years, as growth rate slows, the iron stores start to build and the risk of iron deficiency decreases

60
Q

(TRUE/FALSE)

Throughout adulthood iron stores gradully decrease in men.

A

FALSE

They INCREASE in men.

61
Q

In women, iron stores are XXXX until menopause, after which they increase.

A

LOW until menopause

62
Q

Where is iron mainly excreted?

A

In the feces (0.6 mg/day) in the feces, from bile, dead mucosal cells and the loss of very small amounts of blood

It is also lost in SKIN cells and in SWEAT (0.2-0.3 mg/day)

URINARY losses are minor (<0.1 mg/day)

63
Q

What is the average loss of iron with a menstrual cycle?

A

An average period results in a blood loss of 30-40 ml/cycle, which translates to 0.4-0.5 mg/day iron losses.

BUT combined with other losses, it equates to 1.3 MG/DAY

64
Q

(TRUE/FALSE)

Iron is recycled in the body.

A

TRUE

RBCs destruction and production is responsible for most turnover. Most of the iron from degraded RBCs is recycled and used for the synthesis of HEMOGLOBIN in new RBCs

Remember: RBCs last about 120 days and they contain up to ~2/3 of the total body iron (in the hemoglobin).

65
Q

Which form of iron utilizes the HCP1 at the brush border membrane for absorption?

A

Heme **

HCP1 = Heme Carrier Protein 1

66
Q

Which form of iron utilizes the DMT-1 at the brush border membrane for absorption?

A

Fe2+ FERROUS

Divalent Mineral Transporter 1

67
Q

Which form of iron utilizes Integrin at the brush border membrane for absorption?

A

Fe3+ FERRIC

It is then reduced to Ferrous in the enterocyte via REDUCTASE enzyme

68
Q

What is the role of Heme Oxygenase?

A

In the enterocyte, it is an enzyme that breaks down heme, releasing Fe for absorption

69
Q

What is involved in iron homeostasis? **

A

HEPCIDIN (hormone, secreted by the liver)when iron stores are getting too HIGH. It will bind FERROPORTIN and block it from being able to export any further iron from the enterocyte. So eventually the iron will be lost through enterocyte slough-age when the cells turnover every 4-5 days.

Hepcidin is also synthesized during inflammatory responses, ultimately product consequent systemic iron withdrawal and sequestration.

HYPOXIA TURNS ON IRON UPTAKE: Increasing DMT1 and DcytB

NHM 561 (21 decks)

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