Iron

Iron
• Ferrous state (Fe2+) or ferric state (Fe3+)
• Iron deficiency is common
• Iron is found in animal and plant foods
• Heme iron (25%–35% absorption); more
readily absorbed
• Non heme iron (2%–20% absorption)
• 2-4 g iron in the human body
– 65% in hemoglobin – RBC (oxygen transporter
throughout the body)
– 10% in myoglobin – muscle (oxygen transporter for the
muscles)
– 1-5% as part of enzymes
– Remaining as storage
 Ferritin and Hemosiderin
 Iron

• Heme and nonheme forms

– Heme iron: meat, fish, and poultry
– Nonheme iron: main form of iron in plant foods
• Food sources
– Red meats, seafood, legumes, dark green leafy
vegetables, whole grains, nuts, tofu, and some fruits and
vegetables
• Many grain foods fortified with iron
• Oral supplements of ferrous iron
Iron: heme Iron: non-heme
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Dairy is a poor source of iron
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 Iron Digestion and Absorption

• Heme iron
– Hydrolyzed from hemoglobin/myoglobin in stomach and
small intestine by enzymes
– Absorbed intact by a heme carrier protein (hcp1)
 Bring into intestinal cells
– Hydrolyzed to inorganic ferrous iron (Fe+3) and
protoporphyrin
 Iron Digestion and Absorption (2 of 4)

• Nonheme iron
– Must be hydrolyzed in the GI tract
– Fe3+ reduced to Fe2+ which remains fairly soluble
– Fe2+ passes into small intestine and becomes more
alkaline (2 -> 3)
 Less available for absorption
– Main transporter for Fe2+
 Divalent cation (mineral) transporter DMT1
 Synthesis of DMT1 affected by iron status
• Heme iron
– Hydrolyzed from hemoglobin/myoglobin in stomach and
small intestine by enzymes
– Absorbed intact by a heme carrier protein (hcp1)
– Hydrolyzed to inorganic ferrous iron and protoporphyrin
Iron Digestion and Absorption

EXPORTER
 Iron Digestion and Absorption
1.Iron is released from bound food components. Some HCL in the stomach reduces
Fe3+ to Fe2+.

2. Free heme is absorbed intact by heme carrier protein (hcp1)

3. Within the enterocyte, heme is catabolized by heme oxygenase to protoporphyrin

and Fe2+.

4. Nonheme iron in the small intestine may react with one or more inhibitors, which
promote the fecal excretion of iron.

5. Any of three reductases reduces to Fe2+

6. Divalent metal transporter (DMT1) carries Fe2+ across the brush border
membrane into the cytosol of the enterocyte.

7. Fe2+ may be oxidized Fe3+ to store iron within the cell as part of ferritin.
8. Ferroportin transports iron across the basolateral membrane. Iron transport is
coupled with its oxidation to Fe3+ and transferrin for transport in the blood
Factors Influencing Iron Absorption (Non-heme)

• Inhibitors of nonheme iron absorption

– Polyphenols
– Oxalic acid
– Phytic acid
– Divalent cations
 Calcium
 Zinc
 Manganese
 Intestinal Cell Iron Use

• Once in enterocyte, iron is either:

– Used by intestinal cell in functional capacity
– Stored as ferritin
– Transported across enterocyte’s basolateral membrane
entering circulation for transport to body tissues
 Cellular Iron Uptake

1. Transferrin with its bound Fe3+ atoms attaches to transferrin

receptors on the cell membranes and following attachment,
the complex is endocytosed into the cell cytosol where it
forms an endosome.
2. A drop in pH in the endosome helps initiate the release of
Fe3+which is then reduced by steap3 and transported out of
the endosome by a transporter such as DMT1.
3. The Fe released from the endosome may be:

• Oxidized and stored as ferritin, or

• Oxidized by ceruloplasmin (Cp) and exported from the cell
• Used within the cell functionally such as for heme synthesis, or
Cellular Iron Uptake
 Regulation of Iron Absorption
Enterocyte
• Hepcidin functions to reduce intestinal iron
absorption
– Binds ferroportin
– Limits iron release into the blood
• Hepcidin and inflammation/infection
• Tissue oxygen and erythopoietic activity
Role of the Liver Hormone Hepcidin in Iron Absorption

Hepcidin blocks iron absorption when iron stores are sufficient.

Regulation of Iron Absorption
Liver
 Iron Transport

• Ferric iron in blood is attached to protein transferrin

• Transferrin
– Glycoprotein with two binding sites for minerals
– Binding requires presence of an anion (typically
bicarbonate)
• Plasma iron pool contains about 3–4 mg of iron
bound to transferrin
 Iron Transport

• Unbound iron can generate harmful free radicals

• Free Fe2+ readily reacts with (large amounts with
supplements) H2O2
• Transferrin binds and transports both new and
recycled iron to tissues
• Transferrin half-life
– About 7–10 days
 Iron Storage

• Storage sites
– Liver (mostly), bone marrow, and spleen
• Storage proteins
– Ferritin
 Body and serum stores equalize
– Hemosiderin
 Increases during iron overload
 Iron Functions

• Hemoglobin and myoglobin

– Oxygen delivery
 Iron Functions

• While binding, oxygen oxidizes Fe2+ to Fe3+, this is

the reason why initially iron should be in Fe2+ state.
 Iron Functions

• Cytochromes and other enzymes

– Involved in electron transport chain (TCA)
 Iron Functions

• Monooxygenases and dioxygenases

– Amino acid metabolism
– carnitine synthesis
– procollagen synthesis
• Peroxidases
– Antioxidant roles and thyroid hormone synthesis
• Other iron-containing enzymes
• Iron as a pro-oxidant
Iron Turnover
 Iron Interactions with Other Nutrients

• Vitamin C
– Vitamin C maintains iron in reduced form
• Copper
– Enzymes hephaestin and ceruloplasmin contain copper
• Zinc
– Non-heme iron may compete with zinc for absorption
• Vitamin A
– Vitamin A stimulates erythropoietin production
• Lead
– Multiple interactions (all negative) between lead and iron
 Iron Excretion

• Fecal
– In general, major route of iron excretion
– Endogenous iron losses in feces average 0.6 mg/day
– Losses of iron from blood, bile and sloughing of endothelial cells
• Skin
– Minor route of iron excretion
• Urine
– Minor route of iron excretion
• Menstrual
– For pre-menopausal women, major route of iron excretion
– When averaged over month, iron loss of 0.5 mg/day
 Iron Recommended Dietary Allowance

• Men: 8 mg
• Women:
– Premenopausal: 18 mg
– Postmenopausal: 8 mg
– Pregnancy: 27 mg
– Lactation: 9 mg
 Iron Deficiency

• Deficiency: decreased blood hemoglobin to as low as 7g/100

mL of blood (hypochromic, microcytic anemia)
• Individuals at risk
– Typically due to poor intake and/or high iron losses
• Symptoms
– In children –Reduction in cognitive development and attention,
lethargic, behavior problems
– In adults – Reduced work capacity
– In both – Increased infection, impaired temperature regulation
• Treatment
– Replenishment with iron
 Iron Toxicity

• Tolerable Upper Intake Level: 45 mg

– Acute iron toxicity from accidental iron overload
• Hemochromatosis
– Chronic iron overload
– Genetic disorder
– Body cannot accurately sense iron stores and down-
regulate intestinal absorption
 Iron Assessment of Nutriture

• Progression of deficiency
– First stage: iron stores diminish
 Routine test of plasma (serum) ferritin
– Second stage: transport iron decreases
 Plasma ferritin diminishes, circulating iron begins to decrease
– Continued progression
 Free protoporphyrin rises
– Final stages: anemia occurs
 Hemoglobin and hematocrit typically altered
Effects of virus infections on iron absorption and
storage
• Viral infections change expression of proteins
involved in intestinal iron absorption, such as
hepcidin.

• Viruses utilize cellular iron for replication. Body iron

storage could be depleted as a result of virus
infections.

• While entering iron storage cells, viruses adhere to

transferrin receptors and thus inhibit cellular iron
uptake.