• Scaling of metabolic clearance values from liver microsomal data or recombinantly expressed cytochrome P450 enzymes to predict human hepatic clearance requires knowledge of the amount of microsomal protein per gram of liver (MPPGL). (nih.gov)
  • Phenacetin is metabolized primarily by O-deethylation to paracetamol (POD activity), a reaction catalysed by cytochrome P450. (nih.gov)
  • Warfarin is metabolized via the cytochrome P450 system by CYP 2C9, 1A2, and 3A4. (tag-challenge.com)
  • A reduced rate of lidocaine metabolism following tumescent liposuction may result from an inhibition of cytochrome P450 3A4 (CYP3A4) by sertraline (Zoloft) and flurazepam (Dalmane). (liposuction.com)
  • The specific cytochrome P450 enzyme responsible for the metabolism of flurazepam has not been identified. (liposuction.com)
  • Since 1994 there has been a rapid expansion of information about the specificity of hepatic microsomal enzymes of the cytochrome P450 family for the metabolism of different drugs. (liposuction.com)
  • Effects of probiotic Escherichia coli Nissle 1917 on expression of cytochromes P450 along the gastrointestinal tract of male rats. (nel.edu)
  • The aim of the study was to find whether probiotic Escherichia coli Nissle 1917 O6:K5:H1 (EcN) influences the expression of cytochromes P450 (CYP) in the rat intestine. (nel.edu)
  • Matuskova Z, Tunkova A, Anzenbacherova E, Vecera R, Siller M, Tlaskalova-Hogenova H, Zidek Z, Anzenbacher P. Effects of probiotic Escherichia coli Nissle 1917 on expression of cytochromes P450 along the gastrointestinal tract of male rats. (nel.edu)
  • We investigated the metabolism of 1,8-cineole by liver microsomes of rats and humans and by recombinant cytochrome P450 (P450 or CYP) enzymes in insect cells in which human P450 and NADPH-P450 reductase cDNAs had been introduced. (unboundmedicine.com)
  • 1,8-Cineole was found to be oxidized at high rates to 2-exo-hydroxy-1,8-cineole by rat and human liver microsomal P450 enzymes. (unboundmedicine.com)
  • Primary human hepatocytes in culture are commonly used to evaluate cytochrome P450 (P450) induction via an enzyme activity endpoint. (aspetjournals.org)
  • To this end, the impact of time-dependent P450 inhibition in this system was evaluated. (aspetjournals.org)
  • This work demonstrates that caution is warranted in the interpretation of enzyme induction studies with metabolically stable, weak time-dependent inhibitors, which may have dramatic inhibitory effects on P450 activity in this system. (aspetjournals.org)
  • Therefore, in addition to enzyme activity, mRNA and/or protein levels should be measured to fully evaluate the P450 induction potential of a drug candidate. (aspetjournals.org)
  • An alternative metabolic route was described in which oct-1-ene was converted to a reactive intermediate, octen-3-one, which formed S-3-oxo-octyl-acetylcysteine in in vitro systems using NADPH, cytochrome P450, NAD(P), and N-acetylcysteine (pathway 2). (europa.eu)
  • MeIQx is metabolized by cytochrome P450 1A2 in the human liver into detoxificated and bioactivated products. (peerj.com)
  • An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE . (nih.gov)
  • Cytochromes P450 monooxygenases represent a large superfamily of heme enzymes, which require a dioxygen molecule and two electrons supplied by a NAD(P)H-dependent protein redox partner to form catalytically active high-valent ferryl-oxo intermediate. (schoolbag.info)
  • Cytochromes P450 represent a superfamily of heme enzymes with a common fold and mechanism that requires an atmospheric dioxygen molecule, two electrons from NAD(P)H, and one or two protons available from solvent water to form an active catalytic ferryl-oxo intermediate (1). (schoolbag.info)
  • All cytochromes P450 have one heme b (protoporphyrin IX) buried deeply in the protein globule, with molecular masses in the range 45-60 kDa. (schoolbag.info)
  • Most reactions performed by cytochromes P450 can be catalyzed effectively by Compound I, which is formally the same high-valent intermediate in all isozymes (5, 6). (schoolbag.info)
  • Thus, the broad range of metabolized substrates and the unprecedented variability of the chemical reactions catalyzed by cytochromes P450 can be attributed largely to the differences in substrate binding properties of different isozymes. (schoolbag.info)
  • With respect to their functional roles in living organisms, cytochromes P450 can be separated tentatively into the enzymes essential for biosynthetic pathways and the xenobiotic metabolizing enzymes (1). (schoolbag.info)
  • The former group includes cytochromes P450 involved into the biosynthesis of steroid hormones, antibiotics, and the transformation of vitamins and cofactors such as retinoids, carotenoids, eicosanoids, and fatty acid derivatives as well as those involved in endogenous intracellular and extracellular signaling. (schoolbag.info)
  • As a result, some cytochromes P450 from this group are critical for normal life cycle, and deficiencies can lead to serious diseases (7). (schoolbag.info)
  • In contrast, most cytochromes P450 that belong to the latter group can metabolize a variety of substrates of different sizes through multiple chemical mechanisms and even can form several different products from one substrate. (schoolbag.info)
  • Despite the unprecedented variability of chemical reactions catalyzed by cytochromes P450, all the important features of their mechanism can be attributed to the oxidative transformations driven by the main catalytic intermediate, which is a ferryl-oxo heme complex with the porphyrin pi-cation radical, or Compound I (3, 4, 8). (schoolbag.info)
  • Nonclassic reactions catalyzed by some cytochromes P450, which do not use oxygen, and thus deviate from the main P450 mechanism, include direct reductive processes driven by the heme iron (conversion of nitric oxide to nitrous oxide by CYP55, reductive dehalogenation, reduction of azo compounds and quinines, etc. (schoolbag.info)
  • An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. (edu.au)
  • Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. (unboundmedicine.com)
  • In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufuralol, using liver microsomes from several human samples and human P450 enzymes expressed in human lymphoblastoid cell lines or Escherichia coli. (unboundmedicine.com)
  • Purified recombinant P450 1A2 (expressed in E. coli) produced 1'-, 4-, and 6-hydroxybufuralol in a reconstituted system, although P450 2D6 (expressed in human lymphoblast cell lines) was found to catalyze only bufuralol 1'-hydroxylation. (unboundmedicine.com)
  • Hence, 2-butanol appears to be a very good alcohol substrate for the ethanol-inducible cytochrome P-450. (mssm.edu)
  • Stereochemical studies may be of value in elucidating the mechanism and the identification of the ethanol-inducible cytochrome P-450. (mssm.edu)
  • Pyrazole is oxidized to 4-hydroxypyrazole by rat liver microsomes in a cytochrome P-450-dependent reaction and this oxidation can be increased by prior treatment of rats with pyrazole, 4-methylpyrazole, or chronic ethanol feeding. (elsevierpure.com)
  • The induction pattern suggests that pyrazole may be an effective substrate for oxidation by P-450 IIE.1. (elsevierpure.com)
  • Experiments were carried out to evaluate the ability of anti-3a IgG to inhibit pyrazole oxidation by microsomes from controls and from rats treated with inducers of P-450 IIE.1. (elsevierpure.com)
  • Rates of pyrazole oxidation were highest with microsomes from rats treated with the inducer of P-450 IIE.1 and lowest with pair-fed controls or rats treated with phenobarbital. (elsevierpure.com)
  • The anti-3a IgG-resistant rate of pyrazole oxidation was similar with all the microsomal preparations, and was not due to interaction of pyrazole with hydroxyl radicals. (elsevierpure.com)
  • The anti-3a IgG-sensitive rate of pyrazole oxidation was increased 4- to 5-fold after treatment of rats with pyrazole, 4-methylpyrazole, or ethanol, indicating that the increased oxidation of pyrazole caused by these agents is due to induction of P-450 IIE.1. (elsevierpure.com)
  • Clejan, LA, Koop, DR & Cederbaum, AI 1989, ' Sensitivity of the rat liver microsomal oxidation of pyrazole to antibody raised against the ethanol-inducible rabbit liver cytochrome P-450 isozyme ', Drug Metabolism and Disposition , vol. 17, no. 6, pp. 694-698. (elsevierpure.com)
  • Hepatic microsomal enzymes alter gut-derived chemical substrates by oxidation and by conjugation to glycine and glutathione(GSH) for excretion into bile and for circulation to the kidneys. (antardhwani.org)
  • Similar principles were demonstrated by Leibman and Ortiz (1970), who evaluated the role of epoxides as intermediaries in the microsomal oxidation of olefins to glycols. (europa.eu)
  • 2-Butanol appears to be a particularly good alcohol substrate for the cytochrome P-450 dependent pathway of alcohol oxidation. (mssm.edu)
  • Chronic ethanol consumption, which induces the microsomal alcohol oxidizing system, resulted in a 3-fold increase in the rate of 2-butanol oxidation. (mssm.edu)
  • The rates of oxidation of racemic 2-butanol, (+)-2-butanol, and (-)-2-butanol were the same for (a) model -OH-generating systems, (b) microsomes from chow-fed rats, and (c) microsomes from phenobarbital-treated rats. (mssm.edu)
  • These results suggest that the ·OH-dependent and the cytochrome P-450 dependent pathways of alcohol oxidation by these microsomes do not display stereospecificity. (mssm.edu)
  • Hepatic microsomal monooxygenase systems are the most important enzymes involved in the metabolism of xenobiotics. (cdc.gov)
  • These heme enzymes are found in most organisms from all biological kingdoms and catalyze various oxidative chemical transformations important for the biosynthesis of steroid hormones, vitamins, signaling molecules, and many other compounds, as well as for the metabolism of xenobiotics. (schoolbag.info)
  • The hepatic cytochrome-P-450 monooxygenase system was described. (cdc.gov)
  • The cytochrome P-450 monooxygenase system of the mammalian lung is known to be associated with the microsomal subcellular fraction and has been demonstrated in two pulmonary cell types rich in endoplasmic reticulum: Clara cells and type II pneumocytes. (aspetjournals.org)
  • Kinetic analysis of enzyme inactivation in hepatocytes was used to describe the effect of these time-dependent inhibitors and derive the inhibition parameters k inact and K I , which generally were in good agreement with the values derived using recombinant P450s and human liver microsomes (HLMs). (aspetjournals.org)
  • These data and in vitro metabolism data suggest that, upon multiple dosing, metabolic enzyme inhibition may occur for this drug. (guidelinecentral.com)
  • Some enzymes may also bind simultaneously two or three substrate molecules, same or different, and various cases of the resulting activation or inhibition of the product turnover were documented both in vivo and in vitro (4, 7). (schoolbag.info)
  • These results suggest that 1,8-cineole, a monoterpenoid present in nature, is one of the effective substrates for CYP3A enzymes in rat and human liver microsomes. (unboundmedicine.com)
  • In an in vitro study designed to determine if carbon-carbon double bonds are metabolized to glycols via direct dihydroxylation of the olefinic bond or via epoxide intermediates, complete metabolic conversion of oct-1-ene to glycolic products was accomplished using an NADPH generating system and rat liver microsomes (Maynert et al. (europa.eu)
  • Microsomes have the potential to oxidize alcohols by two pathways, one dependent on hydroxyl radicals (·OH) and the other dependent on cytochrome P-450 in which ·OH does not seem to be involved. (mssm.edu)
  • Thus, the stereochemical preference displayed by microsomes from chronic alcohol fed rats may be due to the induction of a particular cytochrome P-450. (mssm.edu)
  • Ураження печінки, спричинене лікарськими препаратами Many drugs (eg, statins) commonly cause asymptomatic elevation of hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase). (msdmanuals.com)
  • The newer antidepressant selective serotonin reuptake inhibitors (SSRI) such as sertraline are metabolized by the hepatic enzymes CYP3A4 and CYP2D6. (liposuction.com)
  • A porfirina derivada do grupo heme, inativado pela fenelzina, foi isolada e caracterizada como sendo a N-(2-feniletil) protoporfirina IX Assim, o metabolismo da fenelzina, urna alquilidrazina, forma um radical de carbono que pode inativar o citocromo P 450 , ser convertido num hidrocarboneto, reagir com captadores de spin e provavelmente também, pode reagir com biomoléculas circundantes. (usp.br)
  • A carbon radical is formed during the oxidative metabolism of phenelzine that reacts with the prosthetic heme group of cytochrome P 450 and irreversibly inactivates the enzyme. (usp.br)
  • e) Cytochrome aa 3 contains 2 molecules of heme A, each having one Fe atom. (biologydiscussion.com)
  • A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. (curehunter.com)
  • The activity of hepatic drug-metabolizing enzymes in post-mitochondrial fraction and the cytochrome P 450 contents in microsomal fraction decreased significantly, while lysosomal enzymes such as acid phosphatase, acid ribonuclease and cathepsin B showed an increase in the liver homogenates of infected animals. (ias.ac.in)
  • Any compromise of intestinal barrier function increases the production of oxygen radicals and carcinogens by the liver's cytochrome P-450 mixed-function oxidase system. (antardhwani.org)
  • a) Enzymes that catalyse the removal of hy-drogen from a substrate but use only oxy-gen as a hydrogen acceptor to form water as a reaction product (with the exception of uricase and monoamine oxidase which form H 2 O 2 ). (biologydiscussion.com)
  • a) Cytochrome oxidase is a hemoprotein widely distributed in plants and animal tissues. (biologydiscussion.com)
  • 2 at-oms of Cu are also present which are asso-ciated with the cytochrome oxidase ac-tivity. (biologydiscussion.com)
  • g) This enzyme system contains copper, a component of several oxidase enzymes. (biologydiscussion.com)
  • In Lowicryl-embedded sections of lung from adult rabbits, antisera (1:10,000) against the constitutive pulmonary microsomal cytochrome P-450 monooxygenase isozymes 2 and 5 and NADPH-cytochrome P-450 reductase (anti-2, anti-5 and anti-R) bound specifically to regions known to be rich in agranular endoplasmic reticulum (AER) in the cytoplasm of Clara cells. (aspetjournals.org)
  • the cytochrome P-450 content decreased significantly after 14 of the treatments, and cytochrome b 5 and NADPH cytochrome c reductase contents decreased significantly after five and four of the treatments, respectively. (psu.edu)
  • Several cytochrome P-450 isozymes are involved in the metabolism of benzene, although the predominant form is CYP2E1 (Gut et al. (cdc.gov)
  • 1988). Benzene is initially metabolized by cytochrome P-450-dependent mixed function oxidases primarily in the liver via several toxification and detoxification (via conjugation) pathways. (cdc.gov)
  • Our results demonstrate that (1) the detoxification pathway predominates, (2) the ratio between detoxification and bioactivation pathways is not linear and shows a maximum at 10 µM of MeIQx in hepatocyte cell models, and (3) CYP1A2 is a key enzyme in the system that regulates the balance between bioactivation and detoxification. (peerj.com)
  • In enzymology, a methyltetrahydroprotoberberine 14-monooxygenase (EC 1.14.13.37) is an enzyme that catalyzes the chemical reaction (S)-N-methylcanadine + NADPH + H+ + O2 ⇌ {\displaystyle \rightleftharpoons } allocryptopine + NADP+ + H2O The 4 substrates of this enzyme are (S)-N-methylcanadine, NADPH, H+, and O2, whereas its 3 products are allocryptopine, NADP+, and H2O. (wikipedia.org)
  • When two or three drugs are each substrates for the same enzyme, there is a possibility for an adverse drug reaction when used simultaneously. (liposuction.com)
  • similar to that of CYP2C9, thereby obviating kinetic approaches for determining the contribution of the former enzyme to this microsomal drug-metabolizing reaction. (aspetjournals.org)
  • The study incorporates disciplines such as Reaction conditions, Macromolecule, Membrane and Enzyme in addition to Biophysics. (research.com)
  • The powder and alcoholic extract of dried seeds of garden cress were investigated for their effect on metabolic activity of CYP2D6 and CYP3A4 enzymes. (hindawi.com)
  • Dextromethorphan was used as a common marker for measuring metabolic activity of CYP2D6 and CYP3A4 enzymes. (hindawi.com)
  • This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. (wikipedia.org)
  • microsomal fraction, 163 pmol/mg/min). (nih.gov)
  • With all individual samples, microsomal fraction has been prepared and expression of selected CYPs was determined by Western blotting. (nel.edu)
  • Inducers or inhibitors of CYP450 enzymes may change the clearance and therefore the half-life of granisetron. (nih.gov)
  • Elevation of serum phase II enzymes by anticarcinogenic enzyme inducers: markers for a chemoprotected state? (shengsci.com)
  • Inducers of Phase II enzymes, already consumed by humans as food additives, medicines or as constituents of vegetables, can prevent experimental carcinogenesis. (shengsci.com)
  • Although expression of CYP2C19 in human liver is less than that of CYP2C9, it may play an important role in tolbutamide disposition in subjects expressing either high levels of CYP2C19 or a catalytically deficient CYP2C9 enzyme. (aspetjournals.org)
  • His Biochemistry study frequently draws connections between adjacent fields such as Biological system. (research.com)
  • This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity. (curehunter.com)
  • Specific inhibitory antibodies (both monoclonal and monospecific polyclonal) were used to define the specificity of microsomal POD activity. (nih.gov)
  • Enzymes involved in metabolic processes were considered. (cdc.gov)
  • Epoxide formation via cytochrome P-450 dependent processes is similarly subject to steric hindrance, with ready accessibility of the alpha double bond in linear olefins contrasting with the relative inaccessibility of the double bond in internal olefins (Maynert et al. (europa.eu)
  • The metabolic enzyme modulation also leads to incidences of altered bioavailability and pharmacokinetics of therapeutic substrates. (hindawi.com)
  • Hepatic microsomal fractions from phenobarbital induced rabbits were used along with tested compounds xylene, indene, and cyclohexene. (europa.eu)
  • 1964). In vitro metabolism by hepatic microsomal enzymes from rats treated 8 days previously with single i.p. doses of 10 or 100 mg/kg of chlordane in corn oil was increased for the 3 drugs reported (hexobarbital, aminopyrine and chlorpromazine). (inchem.org)
  • However, in recent years, there are large numbers of reports related to herbal toxicity and herb's effects on basic activities such as modulation of drug metabolizing enzymes and drug transporters and interference with bioavailability and pharmacokinetics of concomitantly administered therapeutic substances [ 1 - 3 ]. (hindawi.com)
  • Olefinic structures related to substances included in this category are metabolised to diols via an epoxide intermediate by hepatic microsomal enzymes. (europa.eu)
  • This enzyme participates in alkaloid biosynthesis i. (wikipedia.org)
  • Tolbutamide is a sulfonylurea-type oral hypoglycemic agent whose action is terminated by hydroxylation of the tolylsulfonyl methyl moiety catalyzed by cytochrome P-450 (CYP) enzymes of the human CYP2C subfamily. (aspetjournals.org)
  • However, analysis of ultracellular fractions, isolated cell preparations, or light microscopic immunohistochemical studies of tissue sections has permitted only limited resolution of the distribution of this enzyme system within the 40 or more cell types of the lung. (aspetjournals.org)
  • Immunoblots (Western) of tracheal homogenates yielded no evidence for epitopes other than those in microsomal fractions from whole lung. (aspetjournals.org)
  • The study demonstrated loss of cytochrome P-450 due to alkylation of the haeme function, with mono-oxygenase inactivation occurring to a greater extent with linear and branched alpha olefins relative to that found with internal olefins (with or without branching) where no or minimal loss of cytochrome P-450 was detected. (europa.eu)
  • The possible relations between changes in microsomal cytochromes and polyunsaturated fatty acids is discussed. (psu.edu)
  • Since protection is neither carcinogen- nor organ-specific, clinical trials are already underway to establish the efficacy of 'anticarcinogenic enzyme inducer. (shengsci.com)
  • this P-450 isozyme is recognized by antibody (anti-3a IgG) raised against the ethanol-inducible P-450 in rabbits. (elsevierpure.com)
  • 1986). Oct-1-ene was converted to octane-1,2-oxide which was rapidly hydrolyzed to octane-1,2-diol using an in vitro NADPH generating system (pathway 1). (europa.eu)
  • Most of this increment reflected an increased rate of metabolism by the cytochrome P-450 pathway. (mssm.edu)
  • These differences were observed only for the cytochrome P-450 dependent pathway. (mssm.edu)
  • Montellano and Mico (1980) demonstrated the NADPH-dependent destruction of hepatic microsomal cytochrome P-450 from phenobarbital pre-treated rats by ethylene and other olefins in vitro. (europa.eu)
  • These studies have shown that hepatic high affinity POD activity is exclusively catalysed by cytochrome P450d in both untreated rats and in rats pretreated with MC. (nih.gov)
  • Therefore, we have used the greater resolving power of transmission electron microscopy and immunogold labeling to characterize the cellular and subcellular distribution of the cytochrome P-450 system in the lung. (aspetjournals.org)
  • POBN suitability enabled us to isolate and characterize, by mass spectrometry, the adduct formed during the microsomal metabolism of 3,5-bis( ethoxycarbonyl)-4-ethyl-2,6-dimethyl -1,4-dihydropyridine, as a POBN-ethyl adduct. (usp.br)