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Fibrin (also called Factor Ia) is a
fibrous Fiber (spelled fibre in British English; from ) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often inco ...
, non-globular
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
involved in the
clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation ...
of
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
. It is formed by the action of the
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
thrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...
on
fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...
, which causes it to
polymerize In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many form ...
. The polymerized fibrin, together with
platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
s, forms a
hemostatic An antihemorrhagic () agent is a substance that promotes hemostasis (a process which stops bleeding). It may also be known as a hemostatic (also spelled haemostatic) agent. Antihemorrhagic agents used in medicine have various mechanisms of action: ...
plug or clot over a wound site. When the lining of a blood vessel is broken, platelets are attracted, forming a
platelet plug The platelet plug, also known as the hemostatic plug or platelet thrombus, is an aggregation of platelets formed during early stages of hemostasis in response to one or more injuries to blood vessel walls. After platelets are recruited and begin ...
. These platelets have thrombin receptors on their surfaces that bind serum thrombin molecules, which in turn convert soluble fibrinogen in the serum into fibrin at the wound site. Fibrin forms long strands of tough insoluble protein that are bound to the platelets.
Factor XIII Factor XIII, or fibrin stabilizing factor, is a plasma protein and zymogen. It is activated by thrombin to factor XIIIa which crosslinks fibrin in coagulation. Deficiency of XIII worsens clot stability and increases bleeding tendency. Huma ...
completes the cross-linking of fibrin so that it hardens and contracts. The cross-linked fibrin forms a mesh atop the platelet plug that completes the clot. Fibrin was discovered by
Marcello Malpighi Marcello Malpighi (10 March 1628 – 30 November 1694) was an Italians, Italian biologist and physician, who is referred to as the "founder of microscopical anatomy, histology and father of physiology and embryology". Malpighi's name is borne by ...
in 1666.


Role in disease

Excessive generation of fibrin due to activation of the
coagulation cascade Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulat ...
leads to
thrombosis Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...
, the blockage of a vessel by an
agglutination In linguistics, agglutination is a morphology (linguistics), morphological process in which words are formed by stringing together morphemes (word parts), each of which corresponds to a single Syntax, syntactic feature. Languages that use agglu ...
of red blood cells, platelets, polymerized fibrin and other components. Ineffective generation or premature
lysis Lysis ( ; from Greek 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ...
of fibrin increases the likelihood of a
hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...
. Dysfunction or disease of the liver can lead to a decrease in the production of fibrin's inactive precursor,
fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...
, or to the production of abnormal fibrinogen molecules with reduced activity (
dysfibrinogenaemia The dysfibrinogenemias consist of three types of fibrinogen disorders in which a critical blood clotting factor, fibrinogen, circulates at normal levels but is dysfunctional. Congenital dysfibrinogenemia is an inherited disorder in which one of t ...
). Hereditary abnormalities of fibrinogen (the gene is carried on chromosome 4) are both quantitative and qualitative in nature and include
afibrinogenaemia Congenital afibrinogenemia is a rare, genetically inherited blood fibrinogen disorder in which the blood does not clot normally due to the lack of fibrinogen, a blood protein necessary for coagulation. This disorder is autosomal recessive, meaning ...
,
hypofibrinogenaemia Fibrinolysis syndrome is characterized by an acute hemorrhagic state brought about by inability of the blood to clot, with massive hemorrhages into the skin producing blackish, purplish swellings and sloughing. Symptoms Hemorrhages (this inclu ...
, dysfibrinogenaemia, and
hypodysfibrinogenemia Hypodysfibrinogenemia, also termed congenital hypodysfibrinogenemia, is a rare hereditary fibrinogen disorder cause by mutations in one or more of the genes that encode a factor critical for blood clotting, fibrinogen. These mutations result in th ...
. Reduced, absent, or dysfunctional fibrin is likely to render patients as
hemophiliacs Haemophilia (British English), or hemophilia (American English) (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a long ...
.


Physiology

Fibrin from various different animal sources is generally glycosylated with complex type biantennary asparagine-linked
glycan The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate ...
s. Variety is found in the degree of core
fucosylation Fucosylation is the process of adding fucose sugar units to a molecule. It is a type of glycosylation. It is important clinically, and high levels of fucosylation have been reported in cancer. In cancer and inflammation there are significant chang ...
and in the type of
sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" () was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is ''N''-acetylneuraminic acid ...
and
galactose Galactose (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweetness, sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epime ...
linkage.


Structure

Fibrin is formed after thrombin cleavage of fibrinopeptide A (FPA) from fibrinogen Aalpha-chains, thus initiating fibrin polymerization. Double-stranded fibrils form through end-to-middle domain (D:E) associations, and concomitant lateral fibril associations and branching create a clot network. Fibrin assembly facilitates intermolecular antiparallel C-terminal alignment of gamma-chain pairs, which are then covalently 'cross-linked' by factor XIII ('plasma protransglutaminase') or XIIIa to form 'gamma-dimers'. The image at the left is a crystal structure of the double-d fragment from human fibrin with two bound ligands. The experimental method used to obtain the image was X-ray diffraction, and it has a resolution of 2.30 Å. The structure is mainly made up of single
alpha helices An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
shown in red and
beta sheets The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...
shown in yellow. The two blue structures are the bound
ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...
. The chemical structures of the ligands are Ca2+ ion, alpha-D-mannose (C6H12O6), and
D-glucosamine Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the mos ...
(C6H13NO5).


See also

*
D-dimer D-dimer (or D dimer) is a dimer that is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein ...
*
Fibrin glue Fibrin glue (also called fibrin sealant) is a surgical formulation used to create a fibrin clot for hemostasis, cartilage repair surgeries or wound healing. It contains separately packaged human fibrinogen and human thrombin. Medical uses This ...
* Fibrin scaffold *
Fibrinolysis Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other c ...


References


External links


TGW1916.net
Defibrinated blood harvested from sheep (video)
Fibrin: Molecule of the Month
, by David Goodsell, RCSB Protein Data Bank {{Authority control Coagulation system Blood proteins Acute-phase proteins