RESUMEN
The DoD Cholinesterase Monitoring Program and Cholinesterase Reference Laboratory have safeguarded U.S. government employees in chemical defense for over five decades. Considering Russia's potential deployment of chemical warfare nerve agents in Ukraine, it is critical to maintain a robust cholinesterase testing program and its efficiency presently and in future.
Asunto(s)
Guerra Química , Colinesterasas , Pruebas Enzimáticas Clínicas , Medicina Militar , Humanos , Colinesterasas/historia , Medicina Militar/historia , Guerra Química/historia , Estados Unidos , Pruebas Enzimáticas Clínicas/historiaRESUMEN
For the second half of the XX century, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences was the center of the Russian cholinesterase investigations ("the Russian cholinesterase club"). The close cooperation with chemists-syntheticians of different scientific schools provided success and fruitfulness of this scientific search. All these years, there was preserved dualism of this investigation: a study of the mechanism of functioning and kinetics of cholinesterase catalysis as well as the comparative-enzymological character of studies of cholinesterases of the animals being at different levels of evolutionary development.
Asunto(s)
Bioquímica/historia , Colinesterasas , Ciencia/historia , Animales , Aniversarios y Eventos Especiales , Evolución Biológica , Colinesterasas/química , Colinesterasas/historia , Colinesterasas/fisiología , Historia del Siglo XX , Historia del Siglo XXIRESUMEN
Research on cholinesterases and effects of their inhibition in the USSR and Russia since 1930-1940s till present is exposed in historical aspects. The first physiological and toxicological effects of cholinesterase inhibition were reported by Alexander Ginetsinsky during World War II, when academic institutions were evacuated from Leningrad to Kazan. The main scientific schools that initiated research on chemistry, enzymology and physiology of cholinesterases and their inhibitors were leaded by Alexandr and Boris Arbuzovs, Victor Rozengart, Viktor Yakovlev, Michael Michelson, Martin Kabachnik, Mikhail Voronkov, Ivan Knunyants, Alexandr Bretskin and others. They investigated the main physiological effects of cholinesterase inhibitors, and analyzed the catalytic mechanisms of cholinesterases and related enzymes. Their contributions are landmarks in the history of cholinesterase research. At the present time revival of research on cholinesterases in different universities and institutes is vivid, in particular at the Moscow State University, research institutes of Russian Academy of Sciences and Kazan Scientific Center.
Asunto(s)
Colinesterasas/historia , Academias e Institutos/historia , Animales , Inhibidores de la Colinesterasa/historia , Colinesterasas/metabolismo , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Investigación/historia , Federación de Rusia , U.R.S.S. , Universidades/historiaRESUMEN
In the past four decades of cholinesterase (ChE) research, we have seen substantive evolution of the field from one centered around substrate and inhibitor kinetic profiles and compound characterizations to the analysis of ChE structure, first through the gene families and then by X-ray crystallographic determinations of the free enzymes and their complexes and conjugates. Indeed, these endeavors have been facilitated by recombinant DNA technologies, structure determinations and parallel studies in related proteins in the α/ß-hydrolase fold family. This approach has not only contributed to a fundamental understanding of structure and function of a large family of hydrolase-like proteins possessing functions other than catalysis, but also has been used to develop new practical strategies for scavenging and antidotal activity in cases of organophosphate insecticide or nerve agent exposure.
Asunto(s)
Colinesterasas/historia , Animales , Colinesterasas/química , Colinesterasas/genética , Colinesterasas/metabolismo , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Modelos Moleculares , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/historia , Proteínas del Tejido Nervioso/metabolismo , Pliegue de Proteína , Estructura Terciaria de ProteínaRESUMEN
The classification of the cholinesterases into 'true' and 'pseudo' became obsolete when, some 60 years ago, the author and his co-workers showed that both enzymes had a broad specificity and differed mainly in their acyl group specificity. The importance of complementarity between enzyme and substrate was shown by the high rate of hydrolysis of carbon analogues of choline esters and this enabled pioneer studies of the intermolecular forces between the enzymes' active centres and their substrates to be carried out.