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Micronutrients 4: Iron, Copper & Zinc
iron, copper & zinc
63
Nutrition
Undergraduate 2
04/01/2014

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Cards

Term
What are some dietary sources of iron?
Definition
liver, meat products, plant sources (esp leafy greens)
Term
What are the 3 forms of iron in our diet? Which are organic, which are inorganic?
Definition
Ferrous (Fe2+)
Ferric (Fe3+)
Heme

Heme is organic. Inorganic is a combination of ferric & ferrous iron
Term
What is the bioavailability of heme iron? Ferric iron? Ferrous iron?
Definition
Heme: 20%
Ferrous: poor availability
Ferric: terrible availability
Term
What are the general biological functions of iron?
Definition
1. Oxygen transport (hemoglobin, myoglobin)
2. Redox rxns (important in ETC!)
3. Iron metalloenzymes
Term
How does non-heme dietary iron cross the apical brush border?
Definition
1. HCl + proteases in stomach cleave iron from food components
2. Ferric iron is reduced to ferrous iron by reductase
3. Fe2+ is absorbed via divalent metal transporter 1 (DMT1)
Term
What transporters are involved in bringing dietary iron across the brush border?
Definition
DMT1 mediates Fe2+ import
HCP1 mediates heme iron import
Term
How does heme dietary iron cross the apical brush border?
Definition
1. HCL proteases in stomach release heme iron from hemoglobin/myoglobin
2. Heme porphyrin ring is absorbed via HCP1 transporter
3. Heme oxygenase hydrolyzes heme porphyrin ring, producing Fe2+ & protoporphyrin
Term
What are chelators? What effect do they have on iron absorption?
Definition
Small organic compounds that form a complex with a metal ion. They affect absorption of inorganic iron.

-soluble chelators enhance absorption e.g. amino acids, soluble fibres

-insoluble chelators decrease absorption
e.g. oxalate, phytate, insoluble fibers
Term
What effect does Vit C have on iron absorption?
Definition
acts as a reducing agent & chelator with ferric iron, enhancing absorption of inorganic iron

Fe3+ -> Fe2+
Term
What effect does Vit C have on heme iron absorption?
Definition
None, it only improves absorption of inorganic iron
Term
What happens after inorganic & organic iron have crossed the brush border and are in the intestinal mucosal cell?
Definition
1. Iron pools up in the intestinal musocal cell
2. Ceruloplasmin oxidizes Fe2+ to Fe3+ & binds it to transferrin
3. Transferrin-iron complex travels through the ferroportin transporter & circulates in the bloodstream
Term
What form of iron can move in solution?
Definition
Ferrous (Fe2+)
Term
What form of iron can be bound to proteins for transport or storage?
Definition
Ferric (Fe3+)
Term
How does iron move in the circulatory system?
Definition
bound to a protein called transferrin
Term
How does a cell obtain iron from the blood?
Definition
1. Cell expresses a transferrin-iron complex receptor
2. Receptor binds to cell membrane & is internalized
3. Fe2+ is released & able to be used within the cell
Term
What are some cellular uses of iron?
Definition
-cytochrome production
-iron:sulfur proteins
-iron metalloenzymes
Term
What are metalloenzymes?
Definition
enzymes which require a metal ion to act as a cofactor, enabling them to function
Term
What is ceruloplasmin?
Definition
A copper metalloenzyme which oxidizes ferrous iron to ferric iron & binds it to a tranferrin protein
Term
What transporter carries iron from the intestinal mucosal cell into the bloodstream?
Definition
ferroportin
Term
What is transferrin saturation? At what point is it reached?
Definition
the point at which transferrin will not accept any more iron
-usually around 40% of actual saturation
Term
What happens when the transferrin saturation point is reached?
Definition
-remaining iron in the intestinal mucosal cell is bound to ferritin, forming a storage complex
-intestinal mucosal cell will die & be excreted, taking the excess iron with it
Term
What happens if there is an extreme excess of iron in the diet?
Definition
1. Ferritin complexes will accumulate in the liver
2. Ferritin is oxidized into hemosiderin
3. Hemosiderin can cause liver failure
Term
True or False

Hemosiderosis is more commonly observed in south african tribes due to traditional cooking practices for alcoholic beverages
Definition
True!

However, generally iron toxicity is not commonly observed
Term
How could you treat an iron overload in the diet?
Definition
chelating drugs or blood letting
Term
How is iron excreted once absorbed?
Definition
We have no excretion mechanism once iron is absorbed, which is why excess iron can be toxic (although rare!)
Term
Why might a B6 deficiency lead to anemia?
Definition
-iron molecules in cytochromes, myglobin & hemoglobin are in heme
-heme requires porphyrin synthesis
-porphyrin synthesis requires glycine & Vit B6
Term
What is microcytic hypochromic anemia?
Definition

a condition due to an iron & copper deficiency, characterized by many small, pale RBC's

 

(ceruloplasmin is dysfunctional)

Term
True or False

Poor work performance resulting from an iron deficiency is mainly due to reduced oxygen carrying capacity in the blood
Definition
False

It is mainly due to iron functions within the tissues
Term
True or False

Mild, permanent mental retardation & impaired neural function are a risk of an Fe deficiency
Definition
True
Term
What hormone regulates iron metabolism? How?
Definition
Hepcidin

-binds to ferroportin when TS is reached, preventing more iron from being absorbed into the bloodstream
Term
What is hematopoeisis?
Definition
formation of blood cellular components, requires iron
Term
What are some dietary sources of copper?
Definition
oysters & shellfish
whole grains
beans, nuts, potatoes, dark leafy greens
organ meats
Term
What enzymatic processes is copper a part of?
Definition
1. Iron metabolism (ceruloplasmin)
2. Energy production (cyt. c oxidase)
3. Antioxidant (superoxide dismutase)
4. Norepinephrine production
5. Melanin formation (tyrosine is dependent on Cu)
6. Elastin structure (lysyl oxidase)

Cu acts as an enzyme cofactor & is often a intermediate in redox reactions
Term
What transporters carry copper into intestinal mucosal cells, from the lumen of the SI?
Definition
Copper Trans I (CTR1)
Divalent Metal Transporter 1 (DMT1)
Term
What might affect absorption of dietary Cu?
Definition
soluble ligands (AA's & vit C) increase absorption

insoluble ligands decrease absorption
Term
How does phytate affect the absorption of copper & iron?
Definition
Forms insoluble complexes which decrease absorption
Term
What happens if there is a high percentage of dietary Cu present in intestinal cells?
Definition
-production of the protein metallothionein is induced
-metallothionein traps copper, it will be excreted in the feces when the intestinal cells slough off
Term
Aside from copper, what else might induce metaliothionein? What effect does his have?
Definition
High dietary zinc can also induce this protein
-MT has a higher affinity for copper than zinc though, so this can cause a copper defficiency
Term
Where is copper stored?
Definition
in the liver
Term
How is copper transported from the liver to various tissues?
Definition
via ceruloplasmin
Term
What is the relationship between low ceruloplasmin & copper?
Definition
microcytic hypochromic anemia may occur (secondary iron deficiency), and copper will not be able to be transported to the necessary tissues
Term
What are the symptoms/effects of a copper deficiency?
Definition
-microcytic hypochromic anemia
-depigmentation of skin & hair
-less CuZn superoxid dismutase (SOD) activity = oxidant stress
-reduced lysyl oxidase activity (a copper enzyme) = poor elastin formation, weakened arteries, risk of aortic rupture
Term
In what state is zinc typically found in organs, tissues & body fluids?
Definition
Zn2+
Term
What are some dietary sources of zinc?
Definition
-oysters
-red meat & poultry
-beans, nuts, whole grains
Term
What metabolic functions is zinc associated with?
Definition
-zinc metalloenzymes involved in all metabolic pathways
-oxygen radical metabolism (Cu/Zn superoxide dismutase)
-zinc fingers (DNA binding)
Term
True or False

Zinc & copper participate at the reaction 'active' site of metalloenzymes
Definition
true
Term
How is zinc absorbed in the body?
Definition
1. freed from protein binding by acids in the stomach & small intestine
2. absorbed via ZIP4 & DMT1 transporters
Term
What effect do elevated Zn levels have on Zn absorption?
Definition
-induces metallotionein accumulation & degradation of ZIP4 transporter
-absorption decreases
Term
What transporters are involved with zinc absorption?
Definition
ZIP4 & DMT1
Term
What chelators enhance/inhibit Zn absorption?
Definition
Enhance: some AA's, organic acids e.g. citrate

Inhibit: phytic acid, oxalic acid
Term
True or False

A zinc deficiency is not likely to cause many biological problems
Definition
False

Zinc is involved in over 200 enzymatic activities, a deficiency is problematic!
Term
What is the fate of zinc after it has entered intestinal mucosal cells?
Definition
-used functionally
-bound to metallothionine, stored & excreted
-secreted into circulation, bound to albumin
Term
What is the 1st destination of zinc if it enters the circulatory system?
Definition
the liver
Term
What protein does zinc bind to in order to circulate throughout the body?
Definition
albumin
Term
What are some symptoms/effects of a zinc deficiency?
Definition
-reduced growth in children
-impaired sexual development in males
-malformation of DNA binding proteins & 'zinc fingers'
-inadequate cell division
-poor wound healing
-insufficient taste proteins
Term
What are the effects of an excess of zinc in the diet?
Definition
-induction of metallothionine leads to a copper deficiency
-neurological issues
-numbness
-metallic taste
-nausea
Term
True or False

Zinc is an important component in regulating gene expression
Definition
True

It is found in transcription factors & alters DNA binding of amino acids
Term
What is the importance of magnesium in relation to ATP?
Definition
all metabolically active ATP is bound to magnesium
Term
True or False

Excess calcium intake might impair function of magnesium
Definition
True
Term
What are some symptoms/effects of a Mg deficiency?
Definition
-Type 2 diabetes
-hypertension
-osteoporosis
-colon cancer
-cardiovascular issues
-seizures
-muscle weakness & tremors
-cardiac arrhythmias
Term
Where is manganese primarily found in the body?
Definition
bone
Term
What is the importance of manganese in the urea cycle?
Definition
it is a component of the enzyme arginase, the last step of the urea cycle
Term
What is the metabolic relationship between Mn & biotin?
Definition
Mn & biotin cooperate in gluconeogenesis & fatty acid synthesis
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