Interaction between 2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridine and enzymes of the NADPH-specific electron transport chain of rat liver microsomes

1977 ◽  
Vol 83 (6) ◽  
pp. 794-797
Author(s):  
T. N. Sniedze ◽  
A. P. Shtokman ◽  
V. N. Kiseleva ◽  
T. I. Kagan ◽  
A. P. Gilev
Keyword(s):  
Electron Transport ◽  
Rat Liver ◽  
Electron Transport Chain ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Transport Chain

Analysis of the effects of inhibitors on NADPH-dependent electron transport in rat liver microsomes

1977 ◽  
Vol 26 (5) ◽  
pp. 389-392 ◽  
Author(s):  
Alexander I. Archakov ◽  
Georgy F. Zhirnov ◽  
Irina I. Karuzina
Keyword(s):  
Electron Transport ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria

Hepatology ◽  
1994 ◽  
Vol 19 (2) ◽  
pp. 471-479 ◽  
Author(s):  
Stephan Krähenbühl ◽  
Christine Talos ◽  
Sven Fischer ◽  
Jürg Reichen
Keyword(s):  
Electron Transport ◽  
Bile Acids ◽  
Rat Liver ◽  
Electron Transport Chain ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Isolated Rat Liver ◽  
Transport Chain ◽  
Isolated Rat

scholarly journals Complete inhibition of dihydro-orotate oxidation and superoxide production by 1,1,1-trifluoro-3-thenoylacetone in rat liver mitochondria

1985 ◽  
Vol 225 (1) ◽  
pp. 189-194 ◽  
Author(s):  
K N Dileepan ◽  
J Kennedy
Keyword(s):  
Electron Transport ◽  
Dehydrogenase Activity ◽  
Rat Liver ◽  
Electron Transport Chain ◽  
Chelating Agent ◽  
Liver Mitochondria ◽  
Complete Inhibition ◽  
Rat Liver Mitochondria ◽  
Transport Chain ◽  
A Site

1,1,1-Trifluoro-3-thenoylacetone was shown to cause complete inhibition of dihydroorotate oxidation in rat liver mitochondria as measured by orotate formation and the rate of dihydro-orotate-dependent reduction of 2,6-dichlorophenol-indophenol or cytochrome c. The inhibition by trifluorothenoylacetone was dose-dependent, and a concentration of 1 mM completely inhibited dihydro-orotate dehydrogenase activity. 1,10-Phenanthroline, another iron-chelating agent, also caused total inhibition of the liver enzyme. Whereas the iron chelators inhibited 100% of dihydro-orotate dehydrogenase activity in liver mitochondria, they inhibited only a maximum of 72% in the case of the brain enzyme. The inhibition by trifluorothenoylacetone was not prevented by addition of phenazine methosulphate or ubiquinone. Dihydro-orotate dehydrogenase-mediated generation of superoxide was abolished when the enzyme was fully inhibited by trifluorothenoylacetone or when the electron-transport system was blocked by antimycin A. These results suggest that the iron component(s) of dihydro-orotate dehydrogenase is of strategic importance for catalytic activity and transfer of reducing equivalents from the primary enzyme to the electron-transport chain. Furthermore, the study indicates that production of superoxide radicals during dihydro-orotate dehydrogenase-catalysed oxidation of dihydro-orotate may be at the cytochrome b-c1 segment of the electron-transport chain (as a consequence of autooxidation of ubisemiquinone) rather than at a site on the primary enzyme.

scholarly journals The mitochondrial oxidation of quinol monophosphates

1970 ◽  
Vol 118 (5) ◽  
pp. 719-731
Author(s):  
J. M. Young
Keyword(s):  
Electron Transport ◽  
Cytochrome C ◽  
Oxygen Uptake ◽  
Cytochrome Oxidase ◽  
Rat Liver ◽  
Mode Of Action ◽  
Electron Transport Chain ◽  
Rapid Reduction ◽  
Transport Chain ◽  
Mitochondrial Oxidation

1. Mitochondria from ox heart and rat liver catalysed a slow cyanide-sensitive oxidation of 2,3-dimethylnaphthaquinol monophosphate, duroquinol monophosphate, menadiol 1-phosphate and menadiol 4-phosphate. 2. The release of Pi was concomitant with oxygen uptake. 3. The oxidation was somewhat stimulated by Ca2+ and Pi, and weakly inhibited by 2,4-dinitrophenol. 4. The quinol monophosphates effected a rapid reduction of free cytochrome c, and consequently addition of cytochrome c greatly increased the rate of the mitochondrial oxidation of 2,3-dimethylnaphthaquinol monophosphate. 5. This quinol phosphate interacts with the electron-transport chain at the level of cytochrome c. 6. Polylysine promoted an interaction between 2,3-dimethylnaphthaquinol monophosphate and cytochrome oxidase. Thus, although polylysine blocks mitochondrial oxidations via reduced cytochrome c, the oxidation of the quinol phosphate was strongly stimulated. 7. This stimulation was most effective in the most intact mitochondrial preparations and was inhibited by ADP and by Pi. 8. The implications of these results for factors limiting the rate of quinol phosphate oxidation, the mode of action of stimulators and the mechanism of Pi formation are discussed.

Metabolic Analysis of Triptolide Microspheres in Human, Dog, Rabbit and Rat Liver Microsomes with UPLC-MS/MS Method

2020 ◽  
Vol 17 ◽  
Author(s):  
LiJuan Wang ◽  
Yan Liu ◽  
Rui Li ◽  
DongXian He
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Liver Microsomes ◽  
Good Precision ◽  
Kinetics Parameters ◽  
Measure Concentration ◽  
Standard Curve ◽  
Variation Of Parameters

Objectives: Triptolide (TPL) has been shown to have a good clinical effect on rheumatoid arthritis (RA). We designed TPL microspheres (TPL-MS) and investigated its metabolic behavior in human, dog, rabbit and rat liver microsomes (HLM, DLM, RLM and SDRLM) with UPLC-MS/MS method. Methods: First, a UPLC-MS/MS method was established to measure concentration of TPL in samples. The sample was separated on a C18 column (2.1×100 mm, 1.8μm) and eluted with a gradient elution. The precursor ion/product ion were m/z 378.1/361.0 for TPL and 260.0/116.2 for the internal standard. Then T1/2, Vmax and CLint were calculated from the above data. Finally, the metabolites of TPL-MS were identified by high-resolution UPLC-MS/MS. The sample was separated on a C18 column (2.1×100 mm, 2.2 μm) and eluted with isocratic elution. Mass spectrometric detection was carried out on a thermo Q-exactive mass spectrometer with HESI. The scanning range of precursor ions was from m/z 50 to m/z 750. Result and Discussion: Through several indicators including standard curve, precision, accuracy, stability, matrix effect and recovery rate, the enzymatic kinetics parameters including T1/2, Vmax and CLint were completed. Several metabolites of TPL-MS were identified. Conclusion: UPLC-MS/MS method is an accurate and sensitive method for determination of TPL in liver microsome samples with good precision, accuracy and stability. The variation of parameters indicated that the microspheres can delay the elimination of TPL in liver microsomes. The metabolism of TPL-MS varied among species, but no new metabolites appeared.

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