_Dr. Mohr's lectures_kinins[1].lecture.04

_Dr. Mohr's lectures_kinins[1].lecture.04 - Factor XII...

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Unformatted text preview: Factor XII Factor XIIa Plasma prekallikrein Plasma kallikrein HMW kininogen Bradykinin Inactive peptides Kininases Contact with negative charged surface FXI T p issue rokallikrein Tissue kallikrein Kallidin LMW kininogen ?- - - - - - - - - - - - - - - - - Kinins Overview: Two activation system have been described— Contact System and Endothelial Receptor System Contact System Receptor HK PK/FXI PK/FXI Intact endothelial cell membrane FXII HK Receptor HKa K/FXI BK Endothelial cell membrane Serine protease Receptor HKa K/FXI FXIIa A. B. C. Overview: Endothelial Cell Receptor System Zn 2+ Intact endothelial cell membrane; also platelet and granulocyte membranes FXIIa 3 Kallikreins • Two forms—Plasma and Tissue – Differ in MW, substrate specificity, type of kinin released, functional importance • Acidic glycoproteins • Serine proteases (kininogenases) • Found in biological fluids, glandular tissues, neutrophils HMW kininogen LMW kininogen Plasma pre-kallikrein Tissue kallikrein Ka llid in Plasma kallikrein Br adykinin 4 Plasma kallikrein • Plasma kallikrein, single gene • Synthesized as a zymogen (prekallikrein) in the liver • Prekallikrein circulates bound to HMW kininogen and Factor XI (Plasma Thromboplastic Antecedent) • Kallikrein from action of FXII or binding to HMW K? • Formation of kallikrein requires zinc (1-4 μM) • Plasma kallikrein cleaves bradykinin from HMW kininogen • Major substrate for PK is High Molecular Weight Kininigen (HMK); also LMW kininogen but less preferred • Plasma kallikreins are rapidly inactivated by C1- Inhibitor, a 2-macroglobulin, and antithrombin III 5 Tissue kallikrein • Tissue kallikrein, multiple gene family • Formed first as zymogen: prokallikrien • Tissue kallikrein forms kallidin (Lys-bradykinin) from LMW kininogen (preferred) and HMW kininogen • Some conversion of kallidin to bradykinin may occur by the action of aminopeptidases • Tissue kallikrein gene found in epithelial and secretory cells of ducts – Salivary, sweat, pancreatic , prostatic, intestinal, and distal nephron, endothelium – Tissue kallikrein mRNA found in cultured vascular smooth muscle and in neutrophils 6 Tissue kallikrein • Several proteases in vitro can activate tissue kallikrein from prokallikrein • The in vivo activating enzyme is not known • Inhibitors of tissue kallikrein – Aprotinin, bovine basic pancreatic trypsin inhibitor, kallistatin • Roles in angiogenesis, organogenesis, apoptosis, proliferation T p issue rokallikrein Tissue kallikrein Kallidin LMW kininogen ? 7 Roles for kallikreins Pl Kallikrein Pro-Urokinase Urokinase...
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This note was uploaded on 12/30/2010 for the course PMI 285 taught by Professor Wu during the Winter '04 term at UC Davis.

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_Dr. Mohr's lectures_kinins[1].lecture.04 - Factor XII...

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