Document Detail


Inhibition of p-nitroanisole O-demethylation in perfused rat liver by potassium cyanide.
MedLine Citation:
PMID:  6311107     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of potassium cyanide on p-nitroanisole O-demethylation in perfused rat livers has been examined. Cyanide (2 mM), an inhibitor of cytochrome oxidase, diminished p-nitroanisole O-demethylation by 50-75% in perfused livers from normal and phenobarbital-treated rats, but had much less effect on hepatic microsomal p-nitroanisole O-demethylation. The inhibition was also observed in livers where the activity of the pentose phosphate shunt was abolished by pretreatment with 6-aminonicotinamide. Cyanide infusion decreased hepatic ATP/ADP ratios and cellular concentrations of glutamate, alpha-ketoglutarate, and isocitrate, but caused an increase in the NADP+/NADPH ratio. Rates of NADPH generation via the pentose phosphate shunt were unchanged by cyanide, and hepatic concentrations of glucose 6-phosphate were markedly increased by cyanide. Thus, inhibition of p-nitroanisole metabolism could not be explained solely by a direct interaction of cyanide with mixed-function oxidases or diminished NADPH generation via the pentose cycle. These data indicate that cyanide inhibits mixed-function oxidation in intact cells by diminishing the generation of NADPH from sources other than the pentose cycle. Further, these data are consistent with the hypothesis that some NADPH for mixed-function oxidation arises from cyanide-sensitive mitochondrial sources.
Authors:
L A Reinke; F C Kauffman; S A Belinsky; R G Thurman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  225     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  1983 Aug 
Date Detail:
Created Date:  1983-10-08     Completed Date:  1983-10-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  313-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyanides / pharmacology*
Electron Transport Complex IV / antagonists & inhibitors
Female
Liver / enzymology*
Microsomes, Liver / enzymology
Nitroanisole O-Demethylase / antagonists & inhibitors*
Oxidoreductases / antagonists & inhibitors*
Pentosephosphates / metabolism
Perfusion
Phenobarbital / pharmacology
Potassium Cyanide / pharmacology*
Rats
Rats, Inbred Strains
Grant Support
ID/Acronym/Agency:
CA-20807/CA/NCI NIH HHS; CA-23080/CA/NCI NIH HHS; CA-30137/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cyanides; 0/Pentosephosphates; 151-50-8/Potassium Cyanide; 50-06-6/Phenobarbital; EC 1.-/Nitroanisole O-Demethylase; EC 1.-/Oxidoreductases; EC 1.9.3.1/Electron Transport Complex IV

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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