Linked Life Data

2053846

Source:http://linkedlifedata.com/resource/pubmed/id/2053846

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1991-7-23
pubmed:abstractText
Anaerobic incubation of NADPH- or sodium dithionite-reduced rat liver microsomes with halothane resulted in a significant inactivation of cytochrome P-450 and parallel loss of the prosthetic group protohaem. When the loss of microsomal haem was measured in the same incubations by two different methods, the pyridine/haemochrome assay and the porphyrin fluorescence technique, halothane was responsible for a loss of haem in both assays, indicating that the tetrapyrrolic structure of haem has been modified by halothane metabolites. Cytochrome P-450 loss by halothane was found to be irreversible, saturable, inhibited by carbon monoxide and showed biphasic, pseudo first-order kinetics, thus fulfilling all the conditions of a typical "suicide" inactivation reaction. Pretreatment of rats with inducers of cytochrome P-450 isoenzymes modified the kinetics of cytochrome P-450 inactivation and the amount of total inactivable enzyme in microsomes. A partition ratio, between metabolic turnover of the substrate and enzyme inactivation, of about 121 was found with microsomes from phenobarbital-treated rats, indicating that halothane is rather efficient as a suicide substrate of cytochrome P-450. A stable complex between reduced cytochrome P-450 and a halothane metabolite is responsible for the 470 nm peak observed in the difference spectrum of reduced liver microsomes obtained on addition of halothane. An extinction coefficient for this complex was calculated from the amount of enzyme involved.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0340-5761
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
The mechanism of the suicidal reductive inactivation of microsomal cytochrome P-450 by halothane.
pubmed:affiliation
Istituto di Medicina del Lavoro, Università degli Studi di Padova, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't