| Maintenance of nicotinamide dinucleotide phosphate content and oxidation-reduction state during mixed-function oxidation of p-nitroanisole in isolated perfused livers of various species. | |
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MedLine Citation:
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PMID: 3566803 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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F C Kauffman; R K Evans; A A Jerkins; L A Reinke; J G Conway; R G Thurman |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Biochemical pharmacology Volume: 36 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1987 Apr |
Date Detail:
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Created Date: 1987-05-08 Completed Date: 1987-05-08 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1083-90 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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CA-20807/CA/NCI NIH HHS; CA-23080/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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