Document Detail


Maintenance of nicotinamide dinucleotide phosphate content and oxidation-reduction state during mixed-function oxidation of p-nitroanisole in isolated perfused livers of various species.
MedLine Citation:
PMID:  3566803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The influence of p-nitroanisole, a substrate for mixed-function oxidation, on total NADP+ and NADPH and NADP+/NADPH ratios was examined in perfused livers from three different species. Studies were performed using livers from Sprague-Dawley rats, Syrian golden hamsters and C57BL/6J mice. Although rates of p-nitroanisole O-demethylation varied more than 16-fold in perfused livers from these species, NADP+/NADPH ratios calculated from measured concentrations of NADP+ and NADPH and from ratios calculated from substrate pairs assumed to be in near equilibrium with NADP+-dependent dehydrogenases remained remarkably constant under most conditions. Thus, rates of NADPH utilization and generation must be tightly coupled in perfused livers during high rates of mixed-function oxidation. Exceptions to the general pattern noted above occurred in livers of fasted, phenobarbital-treated rats where carbohydrate reserves were depleted and in livers from 3-methyl-cholanthrene-treated mice where rates of p-nitroanisole O-demethylation were exceptionally high. Livers from fed phenobarbital-treated rats displayed a paradoxical decrease in NADP+/NADPH ratios reflecting reduction calculated from substrates assumed to be in near equilibrium with 6-phosphogluconate dehydrogenase during mixed-function oxidation, suggesting that NADPH generation exceeded NADPH utilization in the rat in the fed state. In contrast, the NADP+/NADPH ratio calculated from measured pyridine nucleotides increased in livers of 3-methylcholanthrene-treated mice perfused with p-nitroanisole, reflecting oxidation. Moreover, the NADP+/NADPH ratio calculated from substrates assumed to be near equilibrium with 6-phosphogluconate dehydrogenase increased in livers of fasted rats, suggesting that utilization of NADPH exceeded generation. Thus, adequate carbohydrate reserves appear essential for maintenance of NADPH during high rates of mixed-function oxidation.
Authors:
F C Kauffman; R K Evans; A A Jerkins; L A Reinke; J G Conway; R G Thurman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  36     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1987 Apr 
Date Detail:
Created Date:  1987-05-08     Completed Date:  1987-05-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1083-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anisoles / metabolism*
Cricetinae
Female
Kinetics
Liver / drug effects,  metabolism*
Male
Mesocricetus
Methylcholanthrene / pharmacology
Mice
Mice, Inbred C57BL
Mixed Function Oxygenases / metabolism*
NADP / metabolism*
Oxidation-Reduction
Perfusion
Phenobarbital / pharmacology
Rats
Rats, Inbred Strains
Species Specificity
Grant Support
ID/Acronym/Agency:
CA-20807/CA/NCI NIH HHS; CA-23080/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Anisoles; 100-17-4/4-nitroanisole; 50-06-6/Phenobarbital; 53-59-8/NADP; 56-49-5/Methylcholanthrene; EC 1.-/Mixed Function Oxygenases

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


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