Search results for "Microsome"

Inhibition of fatty acid delta 6- and delta 5-desaturation by cyclopropene fatty acids in rat liver microsomes.

1993

delta 6-Desaturation of linoleic acid and delta 5-desaturation of dihomo-gamma-linolenic acid were measured in liver microsomes from rats fed fresh Baobab seed oil containing cyclopropene fatty acids (malvalic acid and sterculic acid) or heated Baobab seed oil practically devoid of these fatty acids or control oil. The presence of cyclopropene fatty acids in the fresh Baobab oil diet highly depressed both desaturations, but delta 6- more than delta 5-desaturation. The decreased capacity of microsomes to desaturate was reflected in the lower arachidonic acid content in microsomal phospholipids from rats fed this oil. However it was also lower in rats fed heated oil although in vitro delta 6-…

Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations.

2015

ABSTRACT Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-E…

Phosphorylation of rabbit liver cytochrome P-450 LM2 and its effect on monooxygenase activity

1984

The phosphorylation of rabbit liver microsomal cytochrome P-450 LM2 by catalytic subunit of cyclic AMP-dependent protein kinase (W. Pyerin et al. (1983) Carcinogenesis 4, 573) has now been studied in detail with purified soluble form of cytochrome P-450 as well as with the purified protein incorporated into model membranes. The apparent Km values for P-450 of the phosphorylation reaction in all experimental systems were in a range of 2-8 microM, while the Vmax values were dependent on the state of P-450. Upon phosphorylation, the reconstituted enzyme activities with benzphetamine (N-demethylation) and 7-ethoxycoumarin (O-deethylation) as substrates were reduced to 30-40% of control.

NADPH-cytochrome P-450 reductase: Preferential inhibition by ellipticine and other type II compounds having little effect on NADPH-cytochrome c reduc…

1980

Abstract Ellipticine (5,11-dimethyl-[6H]-pyrido[4,3b]carbazole) binds with an affinity greater than most other compounds known to interact with P-450. Control and 3-methylcholanthrene-induced aryl hydrocarbon (benzo[ a ]pyrene) hydroxylase (EC 1.14.14.2) and acetanilide 4-hydroxylase and control and phenobarbital-induced ethylmorphine N -demethylase activities are all markedly inhibited by ellipticine to about the same extent. Ellipticine and other Type II compounds (metyrapone, octylamine-1, pyridine and aniline) preferentially inhibit NADPH-cytochrome P-450 reductase activity, while affecting NADPH-cytochrome c reductase activity very little. Butanol-1, a compound having pure Reverse Type…

Kinetic experiments on the binding of metyrapone to liver microsomes

1969

Kinetic experiments on the inhibition of oxidative microsomal O- and N-demethylations by metyrapone (2-methyl-1, 2-bis(3-pyridyl)-l-propanone, Su 4885) were carried out using mouse liver microsomes as the enzyme source. The model substrates were p-nitroanisole and N-monomethyl-p-nitroaniline. It was shown that the inhibition is competitive. The K i for metyrapone is 0.42 × 10−4 M and for the reduced metabolite of metyrapone 1.15×10−4 M. Their spectral dissooiation constants as determined from difference spectra have almost the same values. From this it is concluded that the degree of inhibition is correlated to the amount of metyrapone bound to cytochrome P-450. Metyrapone does not seem to …

Biotransformation of methylxanthines in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Allocation of …

1993

V79 Chinese hamster cells genetically engineered for stable expression of single forms of rat cytochromes P450IA1, P450IA2, P450IIB1, human P450IA2, and rat liver epithelial cells expressing murine P450IA2 were used to allocate metabolic pathways of methylxanthines to specific isoforms and to test the suitability of such cell lines for investigations on drug interactions occurring at the cytochrome expressed. The cell lines were exposed to caffeine and/or theophylline and concentrations of metabolites formed in the medium were determined by HPLC. Caffeine was metabolized by human, rat and murine P450IA2, resulting in the formation of four primary demethylated and hydroxylated metabolites. H…

Cytoplasmic autoantigens in autoimmune hepatitis: molecular analysis and clinical relevance.

1991

Biomarker responses of the earthworm Aporrectodea tuberculata to copper and zinc exposure: differences between populations with and without earlier m…

2003

Biomarkers in the earthworm Aporrectodea tuberculata (Eisen) were measured to find out their possible induction under Cu and Zn exposure and differences in the responses between two populations with different exposure history. The biomarkers applied were concentration of metallothioneins (MT), and cytochrome P4501A (CYP1A) monooxygenase and glutathione-S-transferase (GST) activities. These were measured from earthworms sampled at three distances from a steel smelter in Finland and from the individuals from two populations, one with and another without earlier metal exposure, exposed to three combined Cu/Zn concentrations in the laboratory. In the field, MT concentration, and cytochrome CYP1…

ER-to-Golgi Transport: The COPII-Pathway

2006

The endoplasmic reticulum (ER) is the starting site of the journey of newly synthesized proteinsto the apoplast, plasma membrane and to the vacuolar compartments. Transport between these membranecompartments of the secretory pathway in eukaryotic cells is mediated by vesicles, which are producedby a budding mechanism involving coat proteins that capture specific cargo molecules and helppackage them into coated vesicles. These vesicles are known as COPII-coated vesicles, and are usuallyisolated after their induction in vitro using microsomal membranes, cytosol and a non-hydrolyzableGTP-analogue. COPII-coated vesicles are formed at specific sites in the ER known as ER-exit sites(ERES). ERES a…

Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus.

2005

Abstract Background: Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in the liver and intestine by cytochrome P450 3A (CYP3A). Patients with high concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced in these organs, require higher doses of tacrolimus, but the exact mechanism of this association is unknown. Methods: cDNA-expressed CYP3A enzymes and a bank of human liver microsomes with known CYP3A4 and CYP3A5 content were used to investigate the contribution of CYP3A5 to the metabolism of tacrolimus to 13-O-demethyltacrolimus as quantified by liquid chromatography–tandem mass spectrometry. Results: Demethylation of tacrolimus to 13-O-demethyltacrolimus was …