Human iron metabolism - AbsoluteAstronomy.com

Human iron metabolism is the set of chemical reactions maintaining human homeostasis

Human homeostasis

Human homeostasis is derived from the Greek, homeo or "same", and stasis or "stable" and means remaining stable or remaining the same.The human body manages a multitude of highly complex interactions to maintain balance or return systems to functioning within a normal range...

of iron. Iron

Iron

Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

is an essential element

Chemical element

A chemical element is a pure chemical substance consisting of one type of atom distinguished by its atomic number, which is the number of protons in its nucleus. Familiar examples of elements include carbon, oxygen, aluminum, iron, copper, gold, mercury, and lead.As of November 2011, 118 elements...

for most life on Earth

Earth

Earth is the third planet from the Sun, and the densest and fifth-largest of the eight planets in the Solar System. It is also the largest of the Solar System's four terrestrial planets...

, including human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health

Health

Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...

and disease

Disease

A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

. Hematologists have been especially interested in the system of iron metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

because iron is essential to red blood cells. Most of the human body

Human body

The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs.By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life...

's iron is contained in red blood cells. Iron deficiency anemia

Iron deficiency anemia

Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...

is the most common type of anemia

Anemia

Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

.

Understanding this system is also important for understanding diseases of iron overload, like hemochromatosis.

Importance of iron regulation

Iron is an absolute requirement for most forms of life, including humans and most bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

l species, because plants and animal

Animal

Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...

s all use iron; hence, iron can be found in a wide variety of food sources.

Iron is essential to life because of its unusual flexibility to serve as both an electron donor

Electron donor

An electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process....

and acceptor

Electron acceptor

An electron acceptor is a chemical entity that accepts electrons transferred to it from another compound. It is an oxidizing agent that, by virtue of its accepting electrons, is itself reduced in the process....

.

Iron can also be potentially toxic. Its ability to donate and accept electrons means that if iron is free within the cell, it can catalyze

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

the conversion of hydrogen peroxide

Hydrogen peroxide

Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

into free radicals. Free radicals can cause damage to a wide variety of cellular structures, and ultimately kill the cell. To prevent that kind of damage, all life forms that use iron bind the iron atoms to proteins. That allows the cells to use the benefits of iron, but also limit its ability to do harm.

The most important group of iron-binding proteins contain the heme

Heme

A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...

molecules, all of which contain iron at their centers. Humans and most bacteria use variants of heme

Heme

to carry out redox

Redox

Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

reactions and electron transport processes. These reactions and processes are required for oxidative phosphorylation

Oxidative phosphorylation

Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...

. That process is the principal source of energy for human cells; without it, most types of cells would die.

The iron-sulfur protein

Iron-sulfur protein

Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states...

s are another important group of iron-containing proteins. Some of these proteins are also essential parts of oxidative phosphorylation.

Humans also use iron in the hemoglobin

Hemoglobin

Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

of red blood cells, in order to transport oxygen from the lungs to the tissues and to transport carbon dioxide back to the lungs. Iron is also an essential component of myoglobin

Myoglobin

Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...

to store and diffuse oxygen in muscle cells.

The human body needs iron for oxygen transport. That oxygen is required for the production and survival of all cells

Cell (biology)

The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

in our bodies. Human bodies tightly regulate iron absorption and recycling

Recycling

Recycling is processing used materials into new products to prevent waste of potentially useful materials, reduce the consumption of fresh raw materials, reduce energy usage, reduce air pollution and water pollution by reducing the need for "conventional" waste disposal, and lower greenhouse...

. Iron is such an essential element of human life, in fact, that humans have no physiologic regulatory mechanism for excreting

Excretion

Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...

iron. Most humans prevent iron overload solely by regulating iron absorption. Those who cannot regulate absorption well enough get disorders of iron overload. In these diseases, the toxicity of iron starts overwhelming the body's ability to bind and store it.

Bacterial protection

In response to a systemic bacterial infection, the immune system initiates a process known as iron withholding. In iron withholding, the free iron in the plasma binds to transferrin

Transferrin

Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...

, making it harder for bacteria to obtain it. The body cells, however, can easily get iron from transferrin. If bacteria are to survive, then they must obtain iron from their environment. Disease-causing bacteria do this in many ways, including releasing iron-binding molecules called siderophores and then reabsorbing them to recover iron, or scavenging iron from hemoglobin and transferrin. The harder they have to work to get iron, the greater a metabolic price they must pay. That means that iron-deprived bacteria reproduce more slowly. So our control of iron levels appears to be an important defense against bacterial infection. People with increased amounts of iron, like people with hemochromatosis, are more susceptible to bacterial infection.

Although this mechanism is an elegant response to short-term bacterial infection, it can cause problems when inflammation goes on for longer. Since the liver produces hepcidin

Hepcidin

Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...

in response to inflammatory cytokines, hepcidin levels can increase as the result of non-bacterial sources of inflammation, like viral infection, cancer, auto-immune diseases or other chronic diseases. When this occurs, the sequestration of iron appears to be the major cause of the syndrome of anemia of chronic disease

Anemia of chronic disease

Anemia of chronic disease, also referred to as anemia of inflammatory response is a form of anemia seen in chronic illness, e.g. from chronic infection, chronic immune activation, or malignancy...

, in which not enough iron is available to produce enough hemoglobin

Hemoglobin

-containing red blood cells.

Body iron stores

Most well-nourished people in industrialized countries have 4 to 5 grams of iron in their bodies. Of this, about 2.5 g is contained in the hemoglobin needed to carry oxygen through the blood, and most of the rest (approximately 2 grams in adult men, and somewhat less in women of childbearing age) is contained in ferritin

Ferritin

Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...

complexes that are present in all cells, but most common in bone marrow

Bone marrow

Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

, liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, and spleen

Spleen

The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

. The liver's stores of ferritin are the primary physiologic source of reserve iron in the body. The reserves of iron in adults in industrialized countries tend to be lower in children and women of child-bearing age, than in men and in the elderly. Women who must use their stores to compensate for iron lost through menstruation

Menstruation

Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...

, pregnancy

Pregnancy

Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

or lactation

Lactation

Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...

, have lower body stores, which may consist of 500 mg or even less.

Of the body's total iron content, about 400 mg is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin

Myoglobin

), or performing energy-producing redox

Redox

Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

reactions (cytochrome

Cytochrome

Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport.They are found either as monomeric proteins or as subunits of bigger enzymatic complexes that catalyze redox reactions....

s). A relatively small amount (3-4 mg) circulates through the plasma

Blood plasma

Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

, bound to transferrin

Transferrin

. . Because of its toxicity, free soluble iron (soluble ferrous ions Fe(II)) is kept in low concentration in the body.

Iron deficiency first attacks the storage iron in the body, and depletion of these stores is thought to be relatively non-symptomatic, although some vague and non-specific symptoms have been associated with it. Since so much iron is required for hemoglobin, iron deficiency anemia

Iron deficiency anemia

Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...

is the primary clinical manifestation of iron deficiency

Iron deficiency (medicine)

Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...

. Oxygen transport is so important to human life that severe anemia harms or kills people by depriving their organs of enough oxygen. Iron-deficient people will suffer or die from organ damage well before cells run out of the iron needed for intracellular processes like electron transport.

Macrophages of the reticuloendothelial system

Reticuloendothelial system

"Reticuloendothelial system" is an older term for the mononuclear phagocyte system. The mononuclear phagocyte system consists primarily of monocytes and macrophages. The spleen is the largest unit of the mononuclear phagocyte system. The monocyte is formed in the bone marrow and transported by the...

store iron as part of the process of breaking down and processing hemoglobin from engulfed red blood cells.

Iron is also stored as a pigment called hemosiderin

Hemosiderin

thumb|Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderinHemosiderin or haemosiderin is an iron-storage complex. It is always found within cells and appears to be a complex of ferritin, denatured ferritin and other material...

in an apparently pathologic process. This molecule appears to be mainly the result of cell damage. It is often found engulfed by macrophages that are scavenging regions of damage. It can also be found among people with iron overload due to frequent blood cell destruction and transfusions.

How the body gets its iron

Most of the iron in the body is hoarded and recycled by the reticuloendothelial system

Reticuloendothelial system

, which breaks down aged red blood cells. However, people lose a small but steady amount by sweat

SWEAT

SWEAT is an OLN/TSN show hosted by Julie Zwillich that aired in 2003-2004.Each of the 13 half-hour episodes of SWEAT features a different outdoor sport: kayaking, mountain biking, ice hockey, beach volleyball, soccer, windsurfing, rowing, Ultimate, triathlon, wakeboarding, snowboarding, telemark...

ing and by shedding cells of the skin

Skin

-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

and the mucosal lining of the gastrointestinal tract

Gastrointestinal tract

The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

. The total amount of loss for healthy people in the developed world amounts to an estimated average of 1 mg a day for men, and 1.5–2 mg a day for women with regular menstrual periods. People with gastrointestinal parasitic infections, more commonly found in developing countries, often lose more.

This steady loss means that people must continue to absorb iron. They do so via a tightly regulated process that under normal circumstances protects against iron overload.

Absorbing iron from the diet

The absorption of dietary iron is a variable and dynamic process. The amount of iron absorbed compared to the amount ingested is typically low, but may range from 5% to as much as 35% depending on circumstances and type of iron. The efficiency with which iron is absorbed varies depending on the source. Generally the best-absorbed forms of iron come from animal products. Absorption of dietary iron in iron salt form (as in most supplements) varies somewhat according to the body's need for iron, and is usually between 10% and 20% of iron intake. Absorption of iron from animal products, and some plant products, is in the form of heme

Heme

iron, and is more effcient, allowing absorption of from 15% to 35% of intake. Heme iron in animals is from blood and heme containing proteins in meat and mitochondria, whereas in plants, heme iron is present in mitochondria in all cells that use oxygen for respiration.

Like most mineral nutrients, the majority of the iron absorbed from digested food or supplements is absorbed in the duodenum

Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

by enterocyte

Enterocyte

Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase surface area for the digestion and transport of molecules from the intestinal...

s of the duodenal lining. These cells have special molecules that allow them to move iron into the body. To be absorbed, dietary iron can be absorbed as part of a protein such as heme protein or must be in its ferrous Fe²⁺ form. A ferric reductase enzyme on the enterocytes' brush border

Brush border

A brush border is the name for the microvilli-covered surface of simple cuboidal epithelium and simple columnar epithelium cells found in certain locations of the body. Microvilli are approximately 100 nanometers in diameter and their length varies from approximately 100 to 2,000 nanometers in...

, Dcytb, reduces ferric Fe³⁺ to Fe²⁺. A protein called divalent metal transporter 1 DMT1

DMT1

DMT1 is a transporter involved in human iron metabolism. It is located on the apical membrane of duodenal enterocytes and transports Fe2+ from the intestinal lumen to the cytosol....

, which transports all kinds of divalent

Divalent

In chemistry, a divalent ion or molecule has a valence of two and thus can form two bonds with other ions or molecules. An older term for divalent is bivalent....

metals into the body, then transports the iron across the enterocyte's cell membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

and into the cell.

These intestinal lining cells can then either store the iron as ferritin

Ferritin

, which is accomplished by Fe³⁺ binding to apoferritin(in which case the iron will leave the body when the cell dies and is sloughed off into feces

Feces

Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...

) or the cell can move it into the body, using a protein called ferroportin

Ferroportin

Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of it. It is found on the surface of cells that store or transport iron, including:*Enterocytes in the duodenum*Hepatocytes...

. The body regulates iron levels by regulating each of these steps. For instance, cells produce more Dcytb, DMT1 and ferroportin in response to iron deficiency anemia

Iron deficiency anemia

Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...

.

Our bodies' rates of iron absorption appear to respond to a variety of interdependent factors, including total iron stores, the extent to which the bone marrow

Bone marrow

is producing new red blood cells, the concentration of hemoglobin in the blood, and the oxygen content of the blood. We also absorb less iron during times of inflammation

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

. Recent discoveries demonstrate that hepcidin

Hepcidin

regulation of ferroportin (see below) is responsible for the syndrome of anemia of chronic disease

Anemia of chronic disease

Anemia of chronic disease, also referred to as anemia of inflammatory response is a form of anemia seen in chronic illness, e.g. from chronic infection, chronic immune activation, or malignancy...

.

While Dcytb is unique to iron transport across the duodenum, ferroportin

Ferroportin

is distributed throughout the body on all cells which store iron. Thus, regulation of ferroportin

Ferroportin

is the body's main way of regulating the amount of iron in circulation.

Hephaestin

Hephaestin

Hephaestin also known as HEPH is a protein which in humans is encoded by the HEPH gene.-Function:Hephaestin is involved in the metabolism and homeostasis of iron and possibly copper. It is a transmembrane copper-dependent ferroxidase responsible for transporting dietary iron from intestinal...

, a ferroxidase

Ferroxidase

Ferroxidase also known as Fe:oxygen oxidoreductase is an enzyme that catalyzes the oxidization of iron II to iron III:- Examples :Human genes encoding proteins with ferroxidase activity include:* CP – Ceruloplasmin* FTH1 – Ferritin heavy chain...

that which can oxidize Fe²⁺ to Fe³⁺ and is found mainly in the small intestine, helps ferroportin

Ferroportin

transfer iron across the basolateral end of the intestine cells.

Iron absorption from diet is enhanced in the presence of vitamin C and diminished in the presence of calcium.

Reasons for iron deficiency

Functional or actual iron deficiency

Iron deficiency (medicine)

Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...

can result from a variety of causes, explained in more detail in the article dedicated to this topic. These causes can be grouped into several categories:

Increased demand for iron, which the diet cannot accommodate.
Increased loss of iron (usually through loss of blood).
Nutritional deficiency. This can result due to a lack of dietary iron or consumption of foods that inhibit iron absorption, including calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

, phytates and tannins. Contrary to popular belief, persons following vegetarian and vegan diets have similar iron status and the same rates of iron deficiency as non-vegetarians.
Inability to absorb iron because of damage to the intestinal lining. Examples of causes of this kind of damage include surgery involving the duodenum, or diseases like Crohn's or celiac sprue which severely reduce the surface area available for absorption.
Inflammation leading to hepcidin
Hepcidin
Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...

-induced restriction on iron release from enterocytes (see below).

Iron overload

The body is able to substantially reduce the amount of iron it absorbs across the mucosa. It does not seem to be able to entirely shut down the iron transport process. Also, in situations where excess iron damages the intestinal lining itself (for instance, when children eat a large quantity of iron tablets produced for adult consumption), even more iron can enter the bloodstream and cause a potentially deadly syndrome of iron intoxication. Large amounts of free iron in the circulation will cause damage to critical cells in the liver

Liver

, the heart

Heart

The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

and other metabolically active organs.

Iron toxicity results when the amount of circulating iron exceeds the amount of transferrin

Transferrin

available to bind it, but the body is able to vigorously regulate its iron uptake. Thus, iron toxicity from ingestion is usually the result of extraordinary circumstances like iron tablet overdose rather than variations in diet

Diet (nutrition)

In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...

. The type of acute toxicity from iron ingestion causes severe mucosal damage in the gastrointestinal tract, among other problems.

Chronic iron toxicity is usually the result of more chronic iron overload syndromes associated with genetic diseases, repeated transfusions or other causes. In such cases the iron stores of an adult may reach 50 grams (10 times normal total body iron) or more. Classic examples of genetic iron overload includes hereditary hemochromatosis (HH) and the more severe disease juvenile hemochromatosis (JH) caused by mutations in either the gene RGMc gene, a member of a three gene repulsive guidance molecule family , (also called hemojuvelin (HJV), and HFE2), Hemojuvelin

Hemojuvelin

Hemojuvelin is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis in humans, a severe form of hemochromatosis. In humans, the hemojuvelin protein is encoded by the HFE2 gene...

, or the HAMP gene that encodes (an iron regulatory peptide).

How cells get their iron from the body

As discussed above, 60% or more of the iron in the body is located in hemoglobin

Hemoglobin

molecules of red blood cells, and much of the rest is in ferritin

Ferritin

storage form in the liver and other places, the amount of this varying widely between persons. When red blood cells reach a certain age, they are degraded and engulfed by specialized scavenging macrophages. These cells internalize the iron-containing hemoglobin, degrade it, put the iron onto transferrin molecules, and then export the transferrin-iron complexes back out into the blood. Most of the iron used for blood cell production comes from this cycle of hemoglobin recycling.

All cells use some iron, and must get it from the circulating blood

Blood

Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

. Since iron is tightly bound to transferrin, cells throughout the body have receptors for transferrin-iron complexes on their surfaces. These receptors engulf and internalize

Receptor-mediated endocytosis

Receptor-mediated endocytosis , also called clathrin-dependent endocytosis, is a process by which cells internalize molecules by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.-Process:After the binding of a...

both the protein and the iron attached to it. Once inside, the cell transfers the iron to ferritin

Ferritin

, the internal iron storage molecule which is present in all cells.

Transferrin receptor production will increase, and ferritin production will decrease.

Regulation by location

Regulation of iron levels is a task of the whole body, as well as for individual cells.

When body levels of iron are too low, then hepcidin

Hepcidin

in the duodenal epithelium is decreased. This causes an increase in ferroportin

Ferroportin

activity, stimulating iron uptake in the digestive system. The reverse occurs when there is an iron surplus.

In individual cells, an iron deficiency causes responsive element binding protein to iron responsive elements on mRNA for transferrin receptors, resulting in increased production of transferrin receptors. These receptors increase binding of transferrin

Transferrin

to cells, and therefore stimulating iron uptake.

Diseases of iron regulation

The exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic iron overload disorders, remain unsolved. So while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes.

External links

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