Ferritin is a universal intracellular
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that stores
iron
Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...
and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ''intracellular iron-storage protein'' in both
prokaryote
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Conne ...
s and
eukaryotes, keeping iron in a soluble and non-toxic form. In humans, it acts as a buffer against
iron deficiency
Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key ...
and
iron overload
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...
.
Ferritin is found in most tissues as a
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
ic protein, but small amounts are secreted into the
serum where it functions as an iron carrier. Plasma ferritin is also an indirect
marker of the total amount of iron stored in the body; hence, serum ferritin is used as a
diagnostic test
A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic ...
for
iron-deficiency anemia
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
.
Aggregated ferritin transforms into a toxic form of iron called
hemosiderin
Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderin
Hemosiderin or haemosiderin is an iron-storage complex that is composed of partially digested ferritin and lysosomes. The breakdown of heme gives rise ...
.
Ferritin is a
globular protein
In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (formi ...
complex consisting of 24 protein subunits forming a hollow nanocage with multiple metal–protein interactions.
Ferritin that is not combined with iron is called apoferritin.
Gene
Ferritin genes are highly
conserved between species. All vertebrate ferritin genes have three
introns and four
exons.
In human ferritin,
introns are present between
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
residue
Residue may refer to:
Chemistry and biology
* An amino acid, within a peptide chain
* Crop residue, materials left after agricultural processes
* Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...
s 14 and 15, 34 and 35, and 82 and 83; in addition, there are one to two hundred
untranslated bases at either end of the combined exons.
[ The ]tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
residue at amino acid position 27 is thought to be associated with biomineralization
Biomineralization, also written biomineralisation, is the process by which living organisms produce minerals, often to harden or stiffen existing tissues. Such tissues are called mineralized tissues. It is an extremely widespread phenomenon; ...
.
Protein structure
Ferritin is a hollow globular protein
In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (formi ...
of mass 474 kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
and comprising 24 subunits. Typically it has internal and external diameters of about 8 and 12 nm, respectively. The nature of these subunits varies by class of organism:
* In vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...
s, the subunits are of two types, light (L) and heavy (H), which have apparent molecular mass of 19 kDa and 21 kDa, respectively; their sequences are homologous (about 50% identical).[
* Amphibians have an additional ("M") type of ferritin.][
* ]Plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclu ...
s and bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
have a single ferritin; it most closely resembles the vertebrate H-type.[
* In the gastropods of the ]genus
Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...
''Lymnaea
''Lymnaea'' is a genus of small to large-sized air-breathing freshwater snails, aquatic pulmonate gastropod mollusks in the subfamily Lymnaeinae ( of the family Lymnaeidae, the pond snails.Bouchet, P.; Rosenberg, G. (2013). Lymnaea Lamarck, 179 ...
'', two types have been recovered, from somatic cells and the yolk
Among animals which produce eggs, the yolk (; also known as the vitellus) is the nutrient-bearing portion of the egg whose primary function is to supply food for the development of the embryo. Some types of egg contain no yolk, for example ...
, respectively (see below).[
* In the pearl oyster '']Pinctada fucata
''Pinctada fucata'', the Akoya pearl oyster (), is a species of marine bivalve mollusc in the family Pteriidae, the pearl oysters. Some authorities classify this oyster as ''Pinctada imbricata fucata'' (Gould, 1850). It is native to shallow w ...
'', an additional subunit resembling ''Lymnaea'' soma ferritin is associated with shell formation.
* In the parasite '' Schistosoma'', two types are present: one in males, the other in females.[
All the aforementioned ferritins are similar, in terms of their primary sequence, with the vertebrate H-type.][ In ''E. coli'', a 20% similarity to human H-ferritin is observed.][
Some ferritin complexes in vertebrates are ]hetero-oligomer
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
s of two highly related gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
products with slightly different physiological properties. The ratio of the two homologous proteins in the complex depends on the relative expression levels of the two genes.
Inside the ferritin shell, iron ions form crystallite
A crystallite is a small or even microscopic crystal which forms, for example, during the cooling of many materials. Crystallites are also referred to as grains.
Bacillite is a type of crystallite. It is rodlike with parallel longulites.
Stru ...
s together with phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phosph ...
and hydroxide
Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and hydrogen atom held together by a single covalent bond, and carries a negative electric charge. It is an important but usually minor constituent of water. I ...
ions. The resulting particle is similar to ferrihydrite
Ferrihydrite (Fh) is a widespread hydrous ferric oxyhydroxide mineral at the Earth's surface, and a likely constituent in extraterrestrial materials. It forms in several types of environments, from freshwater to marine systems, aquifers to hydr ...
. Each ferritin complex can store about 4500 iron (Fe3+) ions.
A human mitochondrial ferritin
Mitochondrial ferritin is a ferroxidase enzyme that in humans is encoded by the ''FTMT'' gene.
It is classified as a metal-binding protein which is located within the mitochondria. After the protein is taken up by the mitochondria it can be proc ...
, MtF, was found to express as a pro-protein. When a mitochondrion takes it up, it processes it into a mature protein similar to the ferritins found in the cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
, which it assembles to form functional ferritin shells. Unlike other human ferritins, it appears to have no introns
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene ...
in its genetic code. An X-ray diffraction study has revealed that its diameter is 1.70 angstrom
The angstromEntry "angstrom" in the Oxford online dictionary. Retrieved on 2019-03-02 from https://en.oxforddictionaries.com/definition/angstrom.Entry "angstrom" in the Merriam-Webster online dictionary. Retrieved on 2019-03-02 from https://www.m ...
s (0.17 nm), it contains 182 residues, and is 67% helical
Helical may refer to:
* Helix, the mathematical concept for the shape
* Helical engine, a proposed spacecraft propulsion drive
* Helical spring, a coilspring
* Helical plc, a British property company, once a maker of steel bar stock
* Helicoil
A t ...
. The mitochondrial ferritin's Ramachandran plot
In biochemistry, a Ramachandran plot (also known as a Rama plot, a Ramachandran diagram or a ,ψplot), originally developed in 1963 by G. N. Ramachandran, C. Ramakrishnan, and V. Sasisekharan, is a way to visualize energetically allowed regions ...
shows its structure to be mainly alpha helical
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...
with a low prevalence of beta sheets.
Function
Iron storage
Ferritin is present in every cell type.[ It serves to store iron in a non-toxic form, to deposit it in a safe form, and to transport it to areas where it is required. The function and structure of the expressed ferritin protein varies in different cell types. This is controlled primarily by the amount and stability of messenger RNA (mRNA), but also by changes in how the mRNA is stored and how efficiently it is transcribed.] One major trigger for the production of many ferritins is the mere presence of iron;[ an exception is the yolk ferritin of ''Lymnaea sp.'', which lacks an iron-responsive unit.][
Free iron is ]toxic
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...
to cells as it acts as a catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
in the formation of free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
s from reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
via the Fenton reaction. Hence vertebrates have an elaborate set of protective mechanisms to bind iron in various tissue compartments. Within cells, iron is stored in a protein complex as ferritin or the related complex hemosiderin
Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderin
Hemosiderin or haemosiderin is an iron-storage complex that is composed of partially digested ferritin and lysosomes. The breakdown of heme gives rise ...
. Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the reticuloendothelial system
In anatomy the term "reticuloendothelial system" (abbreviated RES), often associated nowadays with the mononuclear phagocyte system (MPS), was originally launched by the beginning of the 20th century to denote a system of specialised cells that eff ...
, protein aggregates are formed as hemosiderin
Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderin
Hemosiderin or haemosiderin is an iron-storage complex that is composed of partially digested ferritin and lysosomes. The breakdown of heme gives rise ...
. Iron in ferritin or hemosiderin can be extracted for release by the RE cells, although hemosiderin is less readily available. Under steady-state conditions, the level of ferritin in the blood serum correlates with total body stores of iron; thus, the serum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores.
Because iron is an important mineral in mineralization, ferritin is employed in the shells of organisms such as molluscs to control the concentration and distribution of iron, thus sculpting shell morphology and colouration. It also plays a role in the haemolymph
Hemolymph, or haemolymph, is a fluid, analogous to the blood in vertebrates, that circulates in the interior of the arthropod (invertebrate) body, remaining in direct contact with the animal's tissues. It is composed of a fluid plasma in which ...
of the polyplacophora, where it serves to rapidly transport iron to the mineralizing radula.
Iron is released from ferritin for use by ferritin degradation, which is performed mainly by lysosome
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pr ...
s.
Ferroxidase activity
Vertebrate ferritin consists of two or three subunits which are named based on their molecular weight: L "light", H "heavy", and M "middle" subunits. The M subunit has only been reported in bullfrogs. In bacteria and archaea, ferritin consists of one subunit type. H and M subunits of eukaryotic ferritin and all subunits of bacterial and archaeal ferritin are H-type and have ferroxidase activity, which is the conversion of iron from the ferrous (Fe2+) to ferric (Fe3+) forms. This limits the deleterious reaction which occurs between ferrous iron and hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...
known as the Fenton reaction which produces the highly damaging hydroxyl radical
The hydroxyl radical is the diatomic molecule . The hydroxyl radical is very stable as a dilute gas, but it decays very rapidly in the condensed phase. It is pervasive in some situations. Most notably the hydroxyl radicals are produced from the ...
. The ferroxidase activity occurs at a diiron binding site in the middle of each H-type subunits. After oxidation of Fe(II), the Fe(III) product stays metastably in the ferroxidase center and is displaced by Fe(II), a mechanism that appears to be common among ferritins of all three kingdoms of life. The light chain of ferritin has no ferroxidase activity but may be responsible for the electron transfer across the protein cage.
Immune response
Ferritin concentrations increase drastically in the presence of an infection or cancer. Endotoxins
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer me ...
are an up-regulator of the gene coding for ferritin, thus causing the concentration of ferritin to rise. By contrast, organisms such as ''Pseudomonas'', although possessing endotoxin, cause plasma ferritin levels to drop significantly within the first 48 hours of infection. Thus, the iron stores of the infected body are denied to the infective agent, impeding its metabolism.
Stress response
The concentration of ferritin has been shown to increase in response to stresses such as anoxia; this implies that it is an acute phase protein.
Mitochondria
Mitochondrial ferritin
Mitochondrial ferritin is a ferroxidase enzyme that in humans is encoded by the ''FTMT'' gene.
It is classified as a metal-binding protein which is located within the mitochondria. After the protein is taken up by the mitochondria it can be proc ...
has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis.
Yolk
In some snails, the protein component of the egg yolk is primarily ferritin; this is a different ferritin, with a different genetic sequence, from the somatic ferritin. It is produced in the midgut glands and secreted into the haemolymph, whence it is transported to the eggs.[
]
Tissue distribution
In vertebrates, ferritin is usually found within cells, although it is also present in smaller quantities in the plasma.[
]
Diagnostic uses
Serum ferritin levels are measured in medical laboratories
A medical laboratory or clinical laboratory is a laboratory where tests are conducted out on clinical specimens to obtain information about the health of a patient to aid in diagnosis, treatment, and prevention of disease. Clinical Medical labor ...
as part of the iron studies workup for iron-deficiency anemia
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
.[ The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of ]anemia of chronic disease
Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin product ...
, where ferritin is elevated in its capacity as an inflammatory acute phase protein and not as a marker for iron overload.
Normal ranges
A normal ferritin blood level, referred to as the reference interval is determined by many testing laboratories. The ranges for ferritin can vary between laboratories but typical ranges would be between 30 and 300 ng/mL (=μg/L) for males, and 30–160 ng/mL (=μg/L) for females. A value less than 50 is considered as iron deficiency.
Deficiency
If the ferritin level is low, there is a risk for lack of iron, which could lead to anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
or iron deficiency without anemia.
In the setting of anemia, low serum ferritin is the most specific lab finding for iron-deficiency anemia
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
. However it is less sensitive, since its levels are increased in the blood by infection or any type of chronic inflammation, and these conditions may convert what would otherwise be a low level of ferritin from lack of iron, into a value in the normal range. For this reason, low ferritin levels carry more information than those in the normal range.
Low ferritin may also indicate hypothyroidism, vitamin C deficiency
Scurvy is a disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding ...
or celiac disease
Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...
.
Low serum ferritin levels are seen in some patients with restless legs syndrome
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...
, not necessarily related to anemia, but perhaps due to low iron stores short of anemia.[
]
A ''falsely low'' blood ferritin (equivalent to a false positive
A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resul ...
test) is very uncommon,[ but can result from a ]hook effect
The hook effect refers to the prozone phenomenon, also known as antibody excess or the Postzone phenomenon, also known as antigen excess. It is an immunologic phenomenon whereby the effectiveness of antibodies to form immune complexes can be impai ...
of the measuring tools in extreme cases.
Vegetarianism is not a cause of low serum ferritin levels, according to the American Dietetic Association's position in 2009: "Incidence of iron-deficiency anemia among vegetarians is similar to that of non-vegetarians. Although vegetarian adults have lower iron stores than non-vegetarians, their serum ferritin levels are usually within the normal range."
Excess
If ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess. For example, ferritins may be high in infection without signaling body iron overload.
Ferritin is also used as a marker for iron overload disorder
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...
s, such as hemochromatosis
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...
or hemosiderosis
Hemosiderosis is a form of iron overload disorder resulting in the accumulation of hemosiderin.
Types include:
* Transfusion hemosiderosis
* Idiopathic pulmonary hemosiderosis
* Transfusional diabetes
Organs affected:
* Hemosiderin deposit ...
. Adult-onset Still's disease
Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagno ...
, some porphyrias, and hemophagocytic lymphohistiocytosis
Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a ...
/macrophage activation syndrome
Macrophage activation syndrome is a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly with systemic-onset juvenile idiopathic arthritis (SoJIA). In addition, MAS has be ...
are diseases in which the ferritin level may be abnormally raised.
As ferritin is also an acute-phase reactant, it is often elevated in the course of disease
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
. A normal C-reactive protein
C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin- ...
can be used to exclude elevated ferritin caused by acute phase reactions.
Ferritin has been shown to be elevated in some cases of COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickly ...
and may correlate with worse clinical outcome.
Ferritin and IL-6 are considered to be possible immunological biomarkers for severe and fatal cases of COVID-19. Ferritin and C-reactive protein may be possible screening tools for early diagnosis of systemic inflammatory response syndrome
Systemic inflammatory response syndrome (SIRS) is an inflammatory state affecting the whole body. It is the body's response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "inflammatory" response, i ...
in cases of COVID-19.
According to a study of anorexia nervosa
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...
patients, ferritin can be elevated during periods of acute malnourishment
Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
, perhaps due to iron going into storage as intravascular volume and thus the number of red blood cells falls.
Another study suggests that due to the catabolic nature of anorexia nervosa
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...
, isoferritins may be released. Furthermore, ferritin has significant non-storage roles within the body, such as protection from oxidative damage
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...
. The rise of these isoferritins may contribute to an overall increase in ferritin concentration. The measurement of ferritin through immunoassay
An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoass ...
or immunoturbidimeteric methods may also be picking up these isoferritins thus not a true reflection of iron storage status.
Studies reveal that a transferrin saturation (serum iron concentration ÷ total iron binding capacity) over 60 percent in men and over 50 percent in women identified the presence of an abnormality in iron metabolism (hereditary hemochromatosis
Hereditary haemochromatosis type 1 (HFE-related Hemochromatosis) is a genetic disorder characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores. Humans, like most animals, h ...
, heterozygotes, and homozygotes) with approximately 95 percent accuracy. This finding helps in the early diagnosis of hereditary hemochromatosis, especially while serum ferritin still remains low. The retained iron in hereditary hemochromatosis is primarily deposited in parenchymal cells, with reticuloendothelial cell accumulation occurring very late in the disease. This is in contrast to transfusional iron overload in which iron deposition occurs first in the reticuloendothelial cells and then in parenchymal cells. This explains why ferritin levels remain relative low in hereditary hemochromatosis, while transferrin saturation is high.
In chronic liver diseases
Hematological abnormalities often associate with chronic liver diseases. Both iron overload and iron deficient anemia have been reported in patients with liver cirrhosis. The former is mainly due to reduced hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.
During conditions in which the hepcidin level is abnormally high, such as inflammation, se ...
level caused by the decreased synthetic capacity of the liver, while the latter is due to acute and chronic bleeding caused by portal hypertension. Inflammation is also present in patients with advanced chronic liver disease. As a consequence, elevated hepatic and serum ferritin levels are consistently reported in chronic liver diseases.
Studies showed association between high serum ferritin levels and increased risk of short-term mortality in cirrhotic patients with acute decompensation and acute-on-chronic liver failure. An other study found association between high serum ferritin levels and increased risk of long-term mortality in compensated and stable decompensated cirrhotic patients. The same study demonstrated that increased serum ferritin levels could predict the development of bacterial infection in stable decompensated cirrhotic patients, while in compensated cirrhotic patients the appearance of the very first acute decompensation episode showed higher incidence in patients with low serum ferritin levels. This latter finding was explaind by the association between chronic bleeding and increased portal pressure.
Applications
Ferritin is used in materials science as a precursor in making iron nanoparticle
A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 10 ...
s for carbon nanotube growth by chemical vapor deposition.
Cavities formed by ferritin and mini-ferritins ( Dps) proteins have been successfully used as the reaction chamber for the fabrication of metal nanoparticles (NPs). Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
shells served as a template to restrain particle growth and as a coating to prevent coagulation/aggregation between NPs. Using various sizes of protein shells, various sizes of NPs can be easily synthesized for chemical, physical and bio-medical applications.
Experimental COVID-19 vaccines have been produced that display the spike protein
In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. as cited in The proteins are usually glycoproteins that form dimers or ...
's receptor binding domain on the surface of ferritin nanoparticles.
Notes
The primary sequence of ferritin is MTTASTSQVR QNYHQDSEAA INRQINLELY ASYVYLSMSY YFDRDDVALK NFAKYFLHQS HEEREHAEKL MKLQNQRGGR IFLQDIKKPD CDDWESGLNA MECALHLEKN VNQSLLEFPS PISPSPSCWH HYTTNRPQPQ HHLLRPRRRK RPHSIPTPIL IFRSP.
See also
* Bacterioferritin
* DNA-binding protein from starved cells
* Ferritin light chain
Ferritin light chain is a protein that in humans is encoded by the ''FTL'' gene. Ferritin is the major protein responsible for storing intracellular iron in prokaryotes and eukaryotes. It is a heteropolymer consisting of 24 subunits, heavy and li ...
* Transferrin
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encode ...
References
External links
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Ferritin
at Lab Tests Online
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{{Blood tests
Iron metabolism
Blood tests
Chemical pathology
Acute-phase proteins
Storage proteins