Characterization of L-amino Acid Oxidase Derived from Venom: Procoagulant and Anticoagulant Activities
Author
Nielsen, Vance GAffiliation
Univ Arizona, Coll Med, Dept AnesthesiolIssue Date
2019-09-30Keywords
L-amino acid oxidaseanticoagulant
carbon monoxide releasing molecule
fibrinogen polymerizing enzyme
procoagulant
thrombelastography
Metadata
Show full item recordPublisher
MDPICitation
Nielsen, V.G. Characterization of L-amino Acid Oxidase Derived from Crotalus adamanteus Venom: Procoagulant and Anticoagulant Activities. Int. J. Mol. Sci. 2019, 20, 4853.Rights
Copyright © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Snake venom enzymes of the L-amino acid oxidase (LAAO) class are responsible for tissue hemorrhage, edema, and derangement of platelet function. However, what role, if any, these flavoenzymes play in altering plasmatic coagulation have not been well defined. Using coagulation kinetomic analyses (thrombelastograph-based), it was determined that the LAAO derived from Crotalus adamanteus venom displayed a procoagulant activity associated with weak clot strength (no factor XIII activation) similar to thrombin-like enzymes. The procoagulant activity was not modified in the presence of reduced glutathione, demonstrating that the procoagulant activity was likely due to deamination, and not hydrogen peroxide generation by the LAAO. Further, unlike the raw venom of the same species, the purified LAAO was not inhibited by carbon monoxide releasing molecule-2 (CORM-2). Lastly, exposure of the enzyme to phenylmethylsulfonyl fluoride (PMSF) resulted in the LAAO expressing anticoagulant activity, preventing contact activation generated thrombin from forming a clot. In sum, this investigation for the first time characterized the LAAO of a snake venom as both a fibrinogen polymerizing and an anticoagulant enzyme acting via oxidative deamination and not proteolysis as is the case with thrombin-like enzymes (e.g., serine proteases). Using this thrombelastographic approach, future investigation of purified enzymes can define their biochemical nature.Note
Open access journalISSN
1422-0067PubMed ID
31574907Version
Final published versionae974a485f413a2113503eed53cd6c53
10.3390/ijms20194853
Scopus Count
Collections
Related articles
- De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses.
- Authors: Nielsen VG, Frank N, Afshar S
- Issue date: 2019 Feb 6
- Carbon monoxide inhibits the anticoagulant activity of phospholipase A<sub>2</sub> purified from Crotalus adamanteus venom.
- Authors: Nielsen VG
- Issue date: 2019 Jan
- Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
- Authors: Naumann GB, Silva LF, Silva L, Faria G, Richardson M, Evangelista K, Kohlhoff M, Gontijo CM, Navdaev A, de Rezende FF, Eble JA, Sanchez EF
- Issue date: 2011 Jul
- Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).
- Authors: Suntravat M, Nuchprayoon I, Pérez JC
- Issue date: 2010 Sep 15
- Biochemical and functional properties of a new l-amino acid oxidase (LAAO) from Micrurus lemniscatus snake venom.
- Authors: Soares TG, Santos JLD, Alvarenga VG, Santos JSC, Leclercq SY, Faria CD, Oliveira MAA, Bemquerer MP, Sanchez EOF, de Lima ME, Figueiredo SG, Borges MH
- Issue date: 2020 Jul 1