1. Chapter 17. Coagulation inhibitors O serpin (serine protease inhibitor) general acid-base catalysis, metal-ion catalysis covalent catalysis (serine)

2. (4) 응고억제

3. 01. Antithrombin III (AT-III) O serpin O heparin, heparan sulfate proteoglycan(HSPGs): negative charge AT-III: rich in lysine (positive charge) O AT-III-alpha form (90%), AT-III-beta form (10%: stronger activity) 4 군데 glycosylation, 3 군데 glycosylation N-glycosidic: asparagine, O-glycosidic: serine, threonine O inhibition: thrombin, Xa, IXa, XIa, XIIa, kallikrein-HMWK, VIIa-TF

4. (1) Heparin 과 antithrombin III O heparin: negative charged heterogeneous mixture anti-coagulant pentasaccharide containing heparin rich in mast cell

5. (2) Phamacologic activation of antithrombin III O standard heparin - above 18 sugar unit, 15-18kD - thrombin, Xa inhibition O low molecular weight heparin (LMWH) - below 18 sugar unit, 7kD - Xa inhibition

6. 02. Heparin cofactor II (HcII, Leuserpin 2) O serpin: AT-III 와 유사 O 유사점 : heparin 과 반응하여 활성도 증가 O 다른점 : thrombin 만을 억제, 임신기간 중 혈전생성 억제 dermatan sulfate proteoglycan 과 반응 (smooth muscle cell, fibroblast 에 주로존재 ) 03. alpha2-macroglobulin O nonspecific serpin O synthesis in liver, fibroblast, macrophage O homotetramer O inhibition: thrombin, kallikrein, plasmin 04. Protein C O vitamin K-dependent: Gla domain O serine protease O inhibition(degradation): Va, VIIIa O EPCR (endothelial cell protein C receptor) thrombomodulin+thrombin Protein C+Protien S (1:1) O protein C deficiency: thrombophilia ( 혈전경향 : 정맥혈전증 )

9. 05. Protein S O synthesis in liver, endothelial cell, megakaryocyte O vitamin K-dependent: gamma-carboxyglutamic acid (Gla domain) O + protein C -> Va, VIIIa inhibition, O deficiency: 정맥혈전증 O 40%: free protein S 60%: C4b-binding protein 과 결합 (1:1) -> inactive state 06. Thrombomodulin (TM) O transmembrane protein in endothelial cell membrane O alpha-thrombin 과 결합 (p174, fig16-15) O protein C, TAFI (thrombin-activatable fibrinolysis inhibitor) 활성화 07. Tissue factor pathway inhibitor (TFPI) O inhibition: VIIa, TF:VIIa complex, Xa, plasmin O synthesis in endothelial cell O 주로 내피세포 표면의 heparan 과 결합되어 있음