Anticoagulant activity of M-LAO, L-amino acid oxidase purified from Agkistrodon halys blomhoffii, through selective inhibition of factor IX.
One of haemorrhagic toxins present in snake venoms is L-amino acid oxidase (LAO), which catalyzes the oxidative deamination of L-amino acids with the generation of hydrogen peroxide. Although it is widely accepted that LAO alters platelet function, the effects of LAO on human blood coagulation remain largely unknown. The present study demonstrated, for the first time, that M-LAO, LAO purified from the venom of Agkistrodon halys blomhoffii (Japanese mamushi), possesses an anticoagulant activity. Thrombelastography (TEG) showed that M-LAO significantly delayed the onset and the progress of the coagulation process. In addition, the enzyme prolonged the activated partial thromboplastin time (aPTT) dose-dependently, but had little effect on the prothrombin time (PT), suggesting that its principal activity was mediated in the intrinsic coagulation pathway. Furthermore, M-LAO reduced factor IX procoagulant activity in a dose-dependent manner and did not affect other coagulation factors. These results indicate that M-LAO has an anticoagulant activity that impairs the intrinsic clotting by inhibiting factor IX.
Sakurai
Yoshihiko
Y
Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Nara Kashihara 634-8522, Japan.
Shima
Midori
M
Matsumoto
Tomoko
T
Takatsuka
Hideo
H
Nishiya
Katsumi
K
Kasuda
Shogo
S
Fujimura
Yoshihiro
Y
Yoshioka
Akira
A
D017836:Agkistrodon; D000594:Amino Acid Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D003435:Crotalid Venoms / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004795:Enzyme Stability; D005164:Factor IX / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050830:L-Amino Acid Oxidase; D011517:Prothrombin Time; D013916:Thrombelastography
D000925:Anticoagulants; D003435:Crotalid Venoms; D005164:Factor IX; D006861:Hydrogen Peroxide; D000594:Amino Acid Oxidoreductases; D050830:L-Amino Acid Oxidase