Search results for "Cytochrome p450"

Enzymatic Biosynthesis of Vomilenine, a Key Intermediate of the Ajmaline Pathway, Catalyzed by a Novel Cytochrome P 450-Dependent Enzyme from Plant C…

1995

Abstract Microsomal preparations from Rauwolfia serpentina Benth. cell suspension cultures cata­lyze a key step in the biosynthesis of ajmaline -the enzymatic hydroxylation of the indole alkaloid vinorine at the allylic C-21 resulting in vomilenine. Vomilenine is an important branch-point intermediate, leading not only to ajmaline but also to several side reactions of the biosynthetic pathway to ajmaline. The investigation of the taxonomical distribution of the enzyme indicated that vinorine hydroxylase is exclusively present in ajmaline-producing plant cells. The novel enzyme is strictly dependent on NADPH2 and O2 and can be inhibited by typical cytochrome P450 inhibitors such as cytochrom…

Epoxide Hydrolase Isoenzymes and their Individual Contribution to the Control of Toxic Metabolites

1991

Epoxides are highly strained three membered cyclic ethers which are formed in vivo by the microsomal cytochrome P450 dependent monooxygenases as intermediates of several important biosynthetic pathways (leukotriene A4, squalene 2, 3-oxide) and as metabolites of numerous xenobiotic compounds containing olefinic or aromatic double bonds. Further transformation of these epoxides may occur by either, rearrangement to phenols, aliphatic aldehydes, or ketones; by cytochrome P450 dependent reduction to the parent compound; or by spontaneous or enzymatic conjugation to gluta-thione. Epoxides may also bind covalently to cellular nucleophiles, such as proteins and nucleic acids thus eliciting carcino…

Rôle des enzymes du métabolisme des xénobiotiques dans la perception de la caféine chez la drosophile

2010

National audience; Les animaux ont développé des systèmes de communication avec leur environnement indispensables à leur survie et leur reproduction. Les systèmes chimiosensoriels gustatifs et olfactifs détectent et transmettent au niveau central les informations chimiques de l’environnement (xénobiotique) afin que l’individu distingue les sources alimentaires des substances toxiques et reconnaisse ses proies de ses congénères. Ces systèmes, pour être efficaces, doivent être très sensibles et discriminants, et éviter la saturation des récepteurs. Dans l’espace péri-récepteur, les enzymes du métabolisme des xénobiotiques (EMX), impliquées normalement dans la détoxication, pourraient égalemen…

Effect of Antioxidants on Microsomal Enzymes of Rat Liver

1978

Rat diet was supplemented with butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) or ethoxyquin (EQ) for 14 days, and hepatic microsomal epoxide hydratase (EH) and monooxygenase were subsequently studied in vitro. The antioxidants increased EH activity. The increase was marked with BHT (factor 3) and EQ (factor 4) and was paralleled by an increase in a protein band on SDS polyacrylamide gels which migrated together with purified rat hepatic EH. A slight but nonsignificant increase in cytochrome P450 content and a moderate increase in ethoxycoumarin deethylation and cytochrome b5 content was also observed while aryl hydrocarbon hydroxylase (AHH) activity was not elevated. Irrever…

External Versus Internal Metabolic Activation of Polycyclic Aromatic Compounds in Mutagenicity Tests: A Comparison Using Heterologous Expression Syst…

1996

Abstract Benzo[a]pyrene-trans-7,8-dihydrodiol was virtually non-mutagenic to Chinese hamster V79p cells, but was strongly mutagenic to a V79-derived cell line expressing cytochrome P450 1A1, when the cells were exposed separately. In mixed cultures of these two cell types, it showed about 50 % of the mutagenic activity in V79p cells, compared to that observed in the enzyme-proficient cell line, indicating an efficient intercellular transfer of the active metabolite. The benzylic alcohols 1-hydroxymethylpyrene and 6-hydroxymethylbenzo[a]-pyrene were weakly mutagenic to Salmonella typhimurium TA1538 in the absence of a metabolic activation system, but were potent mutagens to a TA1538-derived …

Mechanisms involved in lipid accumulation and apoptosis induced by 1-nitropyrene in Hepa1c1c7 cells

2011

International audience; 1-Nitropyrene (1-NP) is a nitro-polycyclic aromatic hydrocarbon (nitro-PAH) present in diesel exhaust and bound to particular matter in urban air. We show that 1-NP and the referent PAH benzo(a)pyrene (BP) induce apoptosis and a lipid accumulation dependent on cytochrome P450 1A1-metabolites in mouse hepatoma cells, whereas 1-amino-pyrene had no effect. The caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-fmk), inhibits 1-NP-induced apoptosis, but failed to alter 1-NP-triggered lipid accumulation determined by Nile red staining. We further show that cholesterol and fatty acid contents are modified after nitro-PAH exposure and that 1…

Effect of cytochrome P450 inhibitors (diethyl dithiocarbamate, ketoconazole and grapefruit juice) on the pharmacokinetics of all-trans-retinoic acid.

2004

Diethyl dithiocarbamate (DEDTC) has been reported to be a more powerful inhibitor of all-trans-retinoic acid (ATRA) in vitro metabolism than the well-established cytochrome P450 (CYP) inhibitor ketoconazole (KC). In recent years grapefruit juice (GJ) has been shown to be able to increase the oral bioavailability of several drugs by inhibiting intestinal CYP. This study investigated the in vivo effect of these CYP inhibitors on the pharmacokinetics of ATRA. The latter was administered to rats as a constant-rate intravenous (i.v.) infusion (0.48 mg h(-1) kg(-1)) during 10 h and orally (1.6 mg kg(-1)). DEDTC (320 mg kg(-1) x 2 i.v., 6.4 and 32 mg kg(-1) per os (p.o.)) did not change the ATRA c…

Cytochrome-P450 phosphorylation as a functional switch

2002

Xenobiotic metabolizing cytochromes P450 (CYP) were shown to be phosphorylated in vitro (using purified protein kinases together with purified CYPs), in intact cells (in V79 cells after transfection of cDNAs coding for individual CYPs, in diagnostic mutants, in hepatocytes), and in whole organisms (rats). CYP phosphorylation is highly isoenzyme selective in that only some CYPs are phosphorylated. Protein kinase A (PKA) was identified as a major catalyst for the phosphorylation of CYPs. The PKA recognition motif Arg-Arg-X-Ser is present in several members of the CYP2 family, but is used by only some of them, most notably by CYP2B1/2B2 and CYP2E1. For CYP2B1 it was shown that a substantial po…

Candidate gene study on nicotine dependence in Finnish sibpairs

2008

Breath test using 13C methacetin does not seem to be useful in the assessment of liver function in girls with anorexia nervosa: a case control study

2018

Abstract Background Anorexia nervosa (AN) concerns approximately up to 1.8% of the pediatric female population. One of the complications that can occur in the course of this disease is acute liver failure. This study’s objective was to assess the usefulness of the 13C labeled Methacetin Breath Test (MBT) in the diagnostics of the liver function in girls with eating disorders. Methods For the study 81 girls aged 12 to 17 years were recruited, including 41 patients with confirmed diagnosis of AN (mean age 14.7 ± 1.48 years) and 40 age-matched controls. The diagnosis was based on the present Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Weight and height were measured…