Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrinogen is a thrombin-coagulable glycoprotein occurring in the blood of vertebrates. The primary structure of the alpha, beta, and gamma polypeptide chains of human fibrinogen is known from amino acid and nucleic acid sequencing. The intact molecule has a trinodular, dimeric structure and is functionally bivalent. Thrombin cleaves short peptides from the amino termini of the alpha and beta chains exposing polymerization sites that are responsible for the formation of fibrin fibers and appearance of a clot. The major physiological function of fibrinogen is the formation of fibrin that binds together platelets and some plasma proteins in a hemostatic plug. In pathological situations, the network entraps large numbers of erythrocytes and leukocytes forming a thrombus that may occlude a blood vessel. Fibrinogen and fibrin are multifunctional proteins. Fibrinogen is indispensable for platelet aggregation; it also binds to several plasma proteins, however, the biological function of this interaction is not completely understood. Fibrin is an essential matrix for regulation of fibrinolysis and for facilitation of cell attachment in wound healing.
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PMID:Fibrinogen and fibrin: biochemistry and pathophysiology. 287 36

When fibers of fibrin clots or fragments of fibrinogen pellets are negatively stained they exhibit in the electron microscope characteristic patterns of cross-striations or bands. Those found in pellet material are indistinguishable from those seen in thrombin-induced fibrin fibers. The pattern seen in fibrin from bovine sources contains three equally spaced faint bands between every two of the broad prominent ones, spaced 23 nm apart. Human material shows a different pattern, one wherein no central faint band is seen, whereas the two remaining ones are broader. Its character is unaffected by crosslinking following fiber formation and preceding negative staining. The bovine pattern, however, is converted by such crosslinking to one that closely resembles the human. It is suggested that the striation pattern in human fibrin is due to juxtapositions of E domains of the parallel-aligned fibrin monomers with tightly coiled COOH-terminal regions of beta and gamma polypeptide chains, with no discernible contribution to the pattern from the alpha chain. In negatively stained untreated fibers of bovine fibrin, however, it is proposed that the COOH-terminal region of the alpha chain becomes tightly coiled, thereby contributing the faint central striation to the band pattern. Crosslinking prevents this conformational change in the alpha chain.
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PMID:Band patterns seen by electron microscopy in ordered arrays of bovine and human fibrinogen and fibrin after negative staining. 657 20

Coagulation profiles were performed in 30 consecutive alcoholic cirrhotic patients without known infection, malignancy, recent surgery, transfusion, or alcoholic intake. Hemorrhagic phenomena were present in 70% and included gastrointestinal bleeding, oozing from venipuncture sites, bruising, and epistaxis. All 30 patients had multiple liver function and coagulation abnormalities, the most frequent of which were increases in F VIII components and decreases in F XI and F VII. Also decreased in half or more of the 30 patients were Fletcher F, F II, F X, prothrombin time (PT), partial thromboplastin time (APTT), thrombin time (TT), reptilase time (RT), anti-thrombin III, and plasminogen. When comparing cirrhotic bleeders with nonbleeders, four parameters were significantly different in those with a bleeding tendency: F VII, anti-thrombin III, plasminogen, and albumin. The prolonged APTT was associated in four cases with a blocking inhibitor of unknown etiology. The prolonged TT and RT, in the absence of fibrin split products, fibrin monomers, DIC, or shortened euglobulin lysis time in any patient were suggestive of an abnormal fibrinogen, a dysfibrinogen. In three other patients, there was an inhibitor of the TT. Further investigation of the suspected dysfibrinogen in 21 patients by SDS-polyacrylamide gel electrophoresis revealed that the molecular weights of the Aalpha, Bbeta, and gamma polypeptide chains of fibrinogen were not different from normal. Two-dimensional immunoelectrophoresis of the suspected dysfibrinogen was similar to normal in 18 of 21 patients, with loss of the initial shoulder in three.
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PMID:Bleeding and coagulation abnormalities in alcoholic cirrhotic liver disease. 704 81

Examples of using monoclonal antibodies (MAb) for studying the fibrin polymerization mechanism are considered. MAb with epitopes situated in the fibrin polymerization sites or in the recognition sites of enzymes thrombin, plasminogen, and factor XIII, which are the functional partners of fibrin, are primarily discussed. The MAb to epitopes in various regions of A alpha, B beta, and gamma polypeptide chains of the functionally important E, D, and alpha C domains of fibrin are successively described.
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PMID:[Monoclonal antibodies as an instrument to study fibrin polymerization]. 1119 89