factor XIII -> factor XIII cleaved tetramer + 2 factor XIII A activation peptides

Stable Identifier
R-HSA-140599
Type
Reaction
Species
Homo sapiens
Compartment
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Some direct oral anticoagulant (DOAC) drugs are potent, competitive direct thrombin inhibitors (DTIs). They reversibly and specifically binds both clot-bound and free thrombin (unlike warfarin or heparin), as well as inhibiting thrombin-induced platelet aggregation. These drugs can be synthetic organic compounds (dabigatran, argatroban) or recombinant peptides (lepirudin, bivalirudin, desirudin). Dabigatran (brand name Pradexa) is formulated as a lipophilic prodrug, dabigatran etexilate, to promote gastrointestinal absorption before it is metabolised to the active drug. The kidneys excrete the majority (80%) of unchanged drug (Stangier et al. 2007). Argatroban is a synthetic inhibitor of thrombin derived from L-arginine, which has a relatively short period of binding only to thrombin’s active site (Hursting et al. 1997). It is given intravenously and is metabolised in the liver. Because of its hepatic metabolism, it may be used in patients with renal dysfunction. Lepirudin (brand name Refludan) is a recombinant hirudin derived from yeast cells (Weitz et al. 1990). Hirudin is a naturally occurring anticoagulant produced by the salivary glands of medicinal leeches. Bivalirudin (brand name Angiomax, Angiox) is a synthetic analog of hirudin, with a shorter period of binding to thrombin (Gladwell 2002). Desirudin (brand name Iprivask) is another recombinant hirudin derivative that directly inhibits free and fibrin-bound thrombin (Graetz et al. 2011). Melagatran is the active drug formed from the prodrug ximelagatran and is a competitive and rapid inhibitor of thrombin (Gustafsson et al. 1998). DuP 714 is a potent and specific thrombin inhibitor (Chiu et al. 1991).

Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers (Lewis et al. 1985). The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.

Literature References
PubMed ID Title Journal Year
2866798 Regulation of formation of factor XIIIa by its fibrin substrates

Lorand, L, Janus, TJ, Shafer, JA, Lewis, SD

Biochemistry 1985
Participants
Participates
Catalyst Activity

serine-type endopeptidase activity of activated thrombin (factor IIa) [extracellular region]

This event is regulated
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