The mechanism of halothane binding to microsomal cytochrome P450 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1974-12

AUTHORS

D. Mansuy, W. Nastainczyk, V. Ullrich

ABSTRACT

The unusual difference spectrum obtained with halothane and reduced rat liver microsomal cytochrome P450 can be simulated by addition of trifluoro diazoethane to dithionite reduced microsomes. Chemical evidence and model reactions suggest that in both cases a trifluoromethyl carbene complex is formed with the reduced hemoprotein. The spectral dissociation constants of the two species are similar as are their competitive reactions with carbon monoxide. The partial destruction of the carbenoid-cytochrome P450 complex characterizes the ligand as a highly reactive species. It is assumed that under anaerobic conditions this complex is formed by a two electron reduction of halothane and that covalent binding to microsomal proteins proceeds by this carbenoid species. A possible relationship to the hepatotoxicity of polyhalogenated compounds and anesthetics is discussed. More... »

PAGES

315-324

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00501461

DOI

http://dx.doi.org/10.1007/bf00501461

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009178910

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/4280521


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