Antithrombinmangel

  • K. Lechner

Zusammenfassung

Antithrombin (AT) ist ein Glykoprotein mit einem Molekulargewicht von 64000 und besteht aus 432 Aminosäuren. Da die Inaktivierung von Thrombin durch AT in Anwesenheit von Heparin beschleunigt wird, wurde AT früher als Heparin-kofaktor I bezeichnet (vgl. Heparinkofaktor II, S. 321). Die funktionell wichtigsten Domänen des AT sind die Heparin- und Thrombinbindungs-stellen. Die Heparinbindungsstellen liegen nahe dem N-terminalen Ende zwischen den Aminosäuren 41 bis 49 und 107 bis 156. Die Thrombin-bindungsstelle liegt nahe dem C-terminalen Ende in einer hydrophoben Tasche (Aminosäuren 382 bis 407). Thrombin spaltet die Bindung Arg 393-Ser 394. Dies hat eine Konformationsänderung des AT-Moleküls zur Folge. Thrombin wird an seiner Bindungsstelle „gefangen“, und es entsteht ein stabiler inaktiver AT-Thrombin-Komplex.

Das AT-Gen liegt im Chromosom 1 (q22–25). Es ist 19 Kilobasen lang und enthält 7 Exons. Exon 2 und 3A kodieren für die heparinbindenden Domänen, Exon 6 für das reaktive Zentrum. Es sind mehrere DNA-Polymorphismen bekannt (Nukleotid- bzw. Aminosäurensubstitutionen ohne Änderung der Funktion oder Sekretion).

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© Springer-Verlag Berlin Heidelberg 1999

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  • K. Lechner

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