Iron Part I

Question 1

How much iron does the human body contain?

Answer 1

~2-4 grams of iron

Question 2

Ferrous Form

Answer 2

Fe2+

Question 3

Ferric Form

Answer 3

Fe3+

Question 4

(TRUE/FALSE)

Men have 3x more iron stores compared to females.

Answer 4

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

Question 5

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

Answer 5

Ferric and Ferrous

Question 6

(TRUE/FALSE)

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

Answer 6

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.

Question 7

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

Answer 7

**
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

Question 8

Explain the chemical structure of heme.

Answer 8

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

Question 9

How is iron transported in the body?

Answer 9

TRANSFERRIN (transport protein)

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

Question 10

How is iron stored in the body?

Answer 10

Ferritin and Hemosiderin

Question 11

What are the two forms of iron found in foods?

Answer 11

1. Heme iron
2. Non-heme iron

Question 12

Heme iron

Answer 12

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**

Question 13

Non-Heme iron

Answer 13

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

–consists primarily of iron salts

Question 14

Is heme or non-heme iron better absorbed?

Answer 14

HEME iron is better absorbed

Question 15

Is heme or non-heme iron better absorbed?

Answer 15

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**

Question 16

What is the main way that we lose iron?

Answer 16

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

Question 17

(TRUE/FALSE)

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

Answer 17

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%.

Question 18

The % of iron absorbed depends on what?

Answer 18

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

Question 19

(TRUE/FALSE)

There are significant differences in absorption potential between genders.

Answer 19

TRUE

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

Question 20

What happens with iron during pregnancy?

Answer 20

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.

Question 21

(TRUE/FALSE)

Iron balance is controlled at the point of absorption.

Answer 21

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%.

Question 22

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

Answer 22

LOWER

GREATER

Question 23

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

Answer 23

~2-20%

Question 24

Absorption of heme iron is XXX%?

Answer 24

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.

Question 25

Explain the absorption of HEME iron.

Answer 25

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

Question 26

Explain the absorption of NON-HEME iron.

Answer 26

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.

Question 27

Heme oxygenase

Answer 27

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

Question 28

Ferroportin

Answer 28

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

Question 29

DMT1

Answer 29

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

Question 30

Ligand

Answer 30

What iron binds to in the enterocyte; provides some solubility

Question 31

Integrin

Answer 31

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

Question 32

Reductase Enzyme

Answer 32

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

Question 33

Dcytb

Answer 33

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

Question 34

Hephaestin

Answer 34

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

Question 35

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).

Answer 35

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.

Question 36

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

Answer 36

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.

Question 37

(TRUE/FALSE) Heme must be hydrolyzed from the globin portion of hemoglobin or myoglobin.

Answer 37

TRUE

Question 38

HCP1

Answer 38

Heme Carrier Protein 1

Question 39

(TRUE/FALSE) Heme is soluble and is readily absorbed INTACT into the enterocyte via XXXX?

Answer 39

TRUE via HCP1 (heme carrier protein 1)

Question 40

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

Answer 40

HEME OXYGENASE

Question 41

Ferric Hydroxide

Answer 41

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

Question 42

Which form of iron is absorbed better?

Answer 42

FERROUS iron is absorbed better than FERRIC iron.

Question 43

Ferritin

Answer 43

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

Question 44

Transferrin

Answer 44

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

Question 45

(TRUE/FALSE) The number of transferrin receptors on the cell surfaces is highly regulated.

Answer 45

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.

Question 46

Hepcidin

Answer 46

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

Question 47

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

Answer 47

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).

Question 48

(TRUE/FALSE) The more oxidized the iron, the most difficult it is for us to absorb it.

Answer 48

TRUE Ferrous is better absorbed than FERRIC

Question 49

What are some factors that INHIBIT iron absorption?

Answer 49

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

Question 50

Why does vitamin C help with iron absorption?

Answer 50

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

Question 51

Where is iron stored?

Answer 51

Liver Bone Marrow Spleen

Question 52

What is the primary storage protein of iron in cells?

Answer 52

FERRITIN

Question 53

What are the two storage proteins of iron in cells?

Answer 53

FERRITIN (primary) HEMOSIDERIN (more long-term storage)

Question 54

How many iron atoms can be stored in ferritin?

Answer 54

~4,500 iron atoms

Question 55

(TRUE/FALSE) Iron bound to hemosiderin is more readily mobilized than iron bound to ferritin.

Answer 55

FALSE It's the other way around Ferritin is more readily mobilized

Question 56

Ferritin consists of how many subunits?

Answer 56

24 subunits

Question 57

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

Answer 57

About 6 months worth (then supplementation will be needed)

Question 58

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

Answer 58

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

Question 59

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.

Answer 59

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

Question 60

(TRUE/FALSE) Throughout adulthood iron stores gradully decrease in men.

Answer 60

FALSE They INCREASE in men.

Question 61

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

Answer 61

LOW until menopause

Question 62

Where is iron mainly excreted?

Answer 62

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)

Question 63

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

Answer 63

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

Question 64

(TRUE/FALSE) Iron is recycled in the body.

Answer 64

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).

Question 65

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

Answer 65

Heme ** HCP1 = Heme Carrier Protein 1

Question 66

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

Answer 66

Fe2+ FERROUS Divalent Mineral Transporter 1

Question 67

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

Answer 67

Fe3+ FERRIC It is then reduced to Ferrous in the enterocyte via REDUCTASE enzyme

Question 68

What is the role of Heme Oxygenase?

Answer 68

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

Question 69

What is involved in iron homeostasis? **

Answer 69

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