Thrombin and haemostasis: regulation of the biological functions of thrombin. (Facts and perspectives).
Thrombin plays an essential role in the maintenance of haemostatic balance through several biochemical reactions. Its functions as well as the regulation of its activities seem to be decisive in controlling thrombus formation. The present paper endeavours to give a brief summary of the control of thrombin activity and the regulation of biological actions of thrombin. As to the control of the amount of the active enzyme, three possible ways are discussed, i.e. prothrombin synthesis, activation of prothrombin, and inactivation of thrombin by plasma proteinase inhibitors (antithrombin III, alpha-2-macroglobulin, alpha-1-proteinase inhibitor). Regarding the regulation of the various actions of thrombin, the most important  biological targets of this enzyme are summarized, namely interaction with fibrinogen, activation of Factor XIII, Factor IX, Factor VIII, Factor V and prothrombin, and the binding to platelets, fibroblasts and endothelial cells. The limits of our present knowledge about the determination of the possible reaction routes catalyzed by thrombin are also considered. Finally, a tentative hypothesis is put forward to explain how the endogenous modulators like heparin determine the biological functions of thrombin.
D000990:Antithrombin III / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004727:Endothelium / Q000378:metabolism; D005164:Factor IX / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005176:Factor XIII / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D011516:Prothrombin / Q000096:biosynthesis / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000515:alpha 1-Antitrypsin / Q000378:metabolism / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000494:pharmacology
D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D000990:Antithrombin III; D005165:Factor V; D011516:Prothrombin; D005169:Factor VIII; D005164:Factor IX; D005340:Fibrinogen; D006493:Heparin; D005176:Factor XIII; D013917:Thrombin