Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)Cytochromes: Hemeproteins whose characteristic mode of action involves transfer of reducing equivalents which are associated with a reversible change in oxidation state of the prosthetic group. Formally, this redox change involves a single-electron, reversible equilibrium between the Fe(II) and Fe(III) states of the central iron atom (From Enzyme Nomenclature, 1992, p539). The various cytochrome subclasses are organized by the type of HEME and by the wavelength range of their reduced alpha-absorption bands.Antipyrine: An analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29)Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Cytochrome P-450 CYP3A: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.Glucaric Acid: A sugar acid derived from D-glucose in which both the aldehydic carbon atom and the carbon atom bearing the primary hydroxyl group are oxidized to carboxylic acid groups.Cytochrome b Group: Cytochromes (electron-transporting proteins) with protoheme (HEME B) as the prosthetic group.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Aryl Hydrocarbon Hydroxylases: A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.Cytochromes b5: Cytochromes of the b group that are found bound to cytoplasmic side of ENDOPLASMIC RETICULUM. They serve as electron carrier proteins for a variety of membrane-bound OXYGENASES. They are reduced by the enzyme CYTOCHROME-B(5) REDUCTASE.Cytochrome P-450 CYP1A1: A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Cytochrome P-450 CYP2E1: An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.Mixed Function Oxygenases: Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.Glutethimide: A hypnotic and sedative. Its use has been largely superseded by other drugs.Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.NADPH-Ferrihemoprotein Reductase: A flavoprotein that catalyzes the reduction of heme-thiolate-dependent monooxygenases and is part of the microsomal hydroxylating system. EC 1.6.2.4.Electron Transport Complex IV: A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane.Cytochrome P-450 CYP2B1: A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Cytochromes c1: The 30-kDa membrane-bound c-type cytochrome protein of mitochondria that functions as an electron donor to CYTOCHROME C GROUP in the mitochondrial and bacterial RESPIRATORY CHAIN. (From Enzyme Nomenclature, 1992, p545)Cytochrome P-450 CYP2D6: A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Adipates: Derivatives of adipic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,6-carboxy terminated aliphatic structure.beta-Naphthoflavone: A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)Kinetics: The rate dynamics in chemical or physical systems.Heparinoids: Heparin derivatives. The term has also been used more loosely to include naturally occurring and synthetic highly-sulphated polysaccharides of similar structure. Heparinoid preparations have been used for a wide range of applications including as anticoagulants and anti-inflammatories and they have been claimed to have hypolipidemic properties. (From Martindale, The Extra Pharmacopoeia, 30th, p232)Cytochromes f: Cytochromes f are found as components of the CYTOCHROME B6F COMPLEX. They play important role in the transfer of electrons from PHOTOSYSTEM I to PHOTOSYSTEM II.FIGLU Test: A urine test for formiminoglutamic acid, an intermediate metabolite in L-histidine catabolism in the conversion of L-histidine to L-glutamic acid. It may be an indicator of vitamin B12 or folic acid deficiency or liver disease.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.Oxidoreductases, N-DemethylatingRNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cytochromes b: Cytochromes of the b group that have alpha-band absorption of 563-564 nm. They occur as subunits in MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III.Metabolic Detoxication, Drug: Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.Oxygenases: Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.TetrahydrocortisoneTyrosine Transaminase: An enzyme that catalyzes the conversion of L-TYROSINE and 2-oxoglutarate to 4-hydroxyphenylpyruvate and L-GLUTAMATE. It is a pyridoxal-phosphate protein. L-PHENYLALANINE is hydroxylated to L-tyrosine. The mitochondrial enzyme may be identical with ASPARTATE AMINOTRANSFERASES (EC 2.6.1.1.). Deficiency of this enzyme may cause type II Tyrosinemia (see TYROSINEMIAS). EC 2.6.1.5.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.NAD(P)H Dehydrogenase (Quinone): A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.Tryptophan Oxygenase: A dioxygenase with specificity for the oxidation of the indoleamine ring of TRYPTOPHAN. It is a LIVER-specific enzyme that is the first and rate limiting enzyme in the kynurenine pathway of TRYPTOPHAN catabolism.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Barbital: A long-acting barbiturate that depresses most metabolic processes at high doses. It is used as a hypnotic and sedative and may induce dependence. Barbital is also used in veterinary practice for central nervous system depression.Cytochrome b6f Complex: A protein complex that includes CYTOCHROME B6 and CYTOCHROME F. It is found in the THYLAKOID MEMBRANE and plays an important role in process of PHOTOSYNTHESIS by transferring electrons from PLASTOQUINONE to PLASTOCYANIN or CYTOCHROME C6. The transfer of electrons is coupled to the transport of PROTONS across the membrane.Cytochromes c2: Type C cytochromes that are small (12-14 kD) single-heme proteins. They function as mobile electron carriers between membrane-bound enzymes in photosynthetic BACTERIA.Toxaphene: A very complex, but reproducible mixture of at least 177 C10 polychloro derivatives, having an approximate overall empirical formula of C10-H10-Cl8. It is used as an insecticide and may reasonably be anticipated to be a carcinogen: Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)Camphor 5-Monooxygenase: A soluble cytochrome P-450 enzyme that catalyzes camphor monooxygenation in the presence of putidaredoxin, putidaredoxin reductase, and molecular oxygen. This enzyme, encoded by the CAMC gene also known as CYP101, has been crystallized from bacteria and the structure is well defined. Under anaerobic conditions, this enzyme reduces the polyhalogenated compounds bound at the camphor-binding site.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Electron Transport: The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270)Primidone: An antiepileptic agent related to the barbiturates; it is partly metabolized to PHENOBARBITAL in the body and owes some of its actions to this metabolite. Adverse effects are reported to be more frequent than with PHENOBARBITAL. (From Martindale, The Extra Pharmacopoeia, 30th ed, p309)Phenytoin: An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.Cytochrome Reductasesgamma-Glutamyltransferase: An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.Aminopyrine N-DemethylaseMolecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.17-Hydroxycorticosteroids: A group of hydroxycorticosteroids bearing a hydroxy group at the 17-position. Urinary excretion of these compounds is used as an index of adrenal function. They are used systemically in the free alcohol form, but with esterification of the hydroxy groups, topical effectiveness is increased.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Aniline Hydroxylase: A drug-metabolizing, cytochrome P-450 enzyme which catalyzes the hydroxylation of aniline to hydroxyaniline in the presence of reduced flavoprotein and molecular oxygen. EC 1.14.14.-.Dactinomycin: A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Steroid 16-alpha-Hydroxylase: A liver microsomal cytochrome P450 enzyme that catalyzes the 16-alpha-hydroxylation of a broad spectrum of steroids, fatty acids, and xenobiotics in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme is encoded by a number of genes from several CYP2 subfamilies.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Microsomes: Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17.Isothiocyanates: Organic compounds with the general formula R-NCS.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Alkane 1-Monooxygenase: A P450 oxidoreductase that catalyzes the hydroxylation of the terminal carbon of linear hydrocarbons such as octane and FATTY ACIDS in the omega position. The enzyme may also play a role in the oxidation of a variety of structurally unrelated compounds such as XENOBIOTICS, and STEROIDS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Anticonvulsants: Drugs used to prevent SEIZURES or reduce their severity.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cytochrome d Group: Cytochromes (electron-transporting proteins) with a tetrapyrrolic chelate of iron as a prosthetic group in which the degree of conjugation of double bonds is less than in porphyrin. (From Enzyme Nomenclature, 1992, p539)Cytochromes a1: A subclass of heme a containing cytochromes have a reduced alpha-band absorption of 587-592 nm. They are primarily found in microorganisms.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.Benzoflavones: Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Rats, Inbred F344Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated S-adenosylmethionine to form spermidine.Steroid 17-alpha-Hydroxylase: A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.Dealkylation: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Liver Neoplasms, Experimental: Experimentally induced tumors of the LIVER.Leucine: An essential branched-chain amino acid important for hemoglobin formation.Proadifen: An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.8,11,14-Eicosatrienoic Acid: A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Organ Size: The measurement of an organ in volume, mass, or heaviness.Anticarcinogenic Agents: Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.Camphor: A bicyclic monoterpene ketone found widely in plants, especially CINNAMOMUM CAMPHORA. It is used topically as a skin antipruritic and as an anti-infective agent.Methylcholanthrene: A carcinogen that is often used in experimental cancer studies.Sulfaphenazole: A sulfonilamide anti-infective agent.Carbon Monoxide: Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)Benzphetamine: A sympathomimetic agent with properties similar to DEXTROAMPHETAMINE. It is used in the treatment of obesity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1222)Cytochromes a: A subclass of heme a containing cytochromes that have two imidazole nitrogens as axial ligands and an alpha-band absorption of 605 nm. They are found in a variety of microorganisms and in eucaryotes as a low-spin cytochrome component of MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Cytochrome-c Peroxidase: A hemeprotein which catalyzes the oxidation of ferrocytochrome c to ferricytochrome c in the presence of hydrogen peroxide. EC 1.11.1.5.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Cytochromes c6: Cytochromes of the c type that are involved in the transfer of electrons from CYTOCHROME B6F COMPLEX and PHOTOSYSTEM I.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Cytochromes c': A widely occurring subclass of c type cytochromes which function as electron carriers in the electron transport chain in photosynthetic and denitrifying BACTERIA.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Tetrachlorodibenzodioxin: A chemical by-product that results from burning or incinerating chlorinated industrial chemicals and other hydrocarbons. This compound is considered an environmental toxin, and may pose reproductive, as well as, other health risks for animals and humans.Adrenodoxin: An iron-sulfur protein which serves as an electron carrier in enzymatic steroid hydroxylation reactions in adrenal cortex mitochondria. The electron transport system which catalyzes this reaction consists of adrenodoxin reductase, NADP, adrenodoxin, and cytochrome P-450.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Carboxy-Lyases: Enzymes that catalyze the addition of a carboxyl group to a compound (carboxylases) or the removal of a carboxyl group from a compound (decarboxylases). EC 4.1.1.Spectrum Analysis: The measurement of the amplitude of the components of a complex waveform throughout the frequency range of the waveform. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Cholesterol Side-Chain Cleavage Enzyme: A mitochondrial cytochrome P450 enzyme that catalyzes the side-chain cleavage of C27 cholesterol to C21 pregnenolone in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11A1 gene, catalyzes the breakage between C20 and C22 which is the initial and rate-limiting step in the biosynthesis of various gonadal and adrenal steroid hormones.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Troleandomycin: A macrolide antibiotic that is similar to ERYTHROMYCIN.Horses: Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Cytochrome-B(5) Reductase: A FLAVOPROTEIN oxidoreductase that occurs both as a soluble enzyme and a membrane-bound enzyme due to ALTERNATIVE SPLICING of a single mRNA. The soluble form is present mainly in ERYTHROCYTES and is involved in the reduction of METHEMOGLOBIN. The membrane-bound form of the enzyme is found primarily in the ENDOPLASMIC RETICULUM and outer mitochondrial membrane, where it participates in the desaturation of FATTY ACIDS; CHOLESTEROL biosynthesis and drug metabolism. A deficiency in the enzyme can result in METHEMOGLOBINEMIA.Oxygen: An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.Aromatase: An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.Receptors, Aryl Hydrocarbon: Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.NADP: Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)Hydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.Electron Spin Resonance Spectroscopy: A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.Ferricyanides: Inorganic salts of the hypothetical acid, H3Fe(CN)6.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Bacterial Proteins: Proteins found in any species of bacterium.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Dithionite: Dithionite. The dithionous acid ion and its salts.Cyanides: Inorganic salts of HYDROGEN CYANIDE containing the -CN radical. The concept also includes isocyanides. It is distinguished from NITRILES, which denotes organic compounds containing the -CN radical.Mice, Inbred C57BLPromoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.NADH, NADPH Oxidoreductases: A group of oxidoreductases that act on NADH or NADPH. In general, enzymes using NADH or NADPH to reduce a substrate are classified according to the reverse reaction, in which NAD+ or NADP+ is formally regarded as an acceptor. This subclass includes only those enzymes in which some other redox carrier is the acceptor. (Enzyme Nomenclature, 1992, p100) EC 1.6.Paracoccus denitrificans: A species of bacteria isolated from soil.Metyrapone: An inhibitor of the enzyme STEROID 11-BETA-MONOOXYGENASE. It is used as a test of the feedback hypothalamic-pituitary mechanism in the diagnosis of CUSHING SYNDROME.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.L-Lactate Dehydrogenase (Cytochrome): A cytochrome form of lactate dehydrogenase found in the MITOCHONDRIA. It catalyzes the oxidation of L-lactate to PYRUVATE with transfer of electrons to CYTOCHROME C. The enzyme utilizes FMN and PROTOHEME IX as cofactors.Embryonic Induction: The complex processes of initiating CELL DIFFERENTIATION in the embryo. The precise regulation by cell interactions leads to diversity of cell types and specific pattern of organization (EMBRYOGENESIS).Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Sterol 14-Demethylase: An NADPH-dependent P450 enzyme that plays an essential role in the sterol biosynthetic pathway by catalyzing the demethylation of 14-methyl sterols such as lanosterol. The enzyme acts via the repeated hydroxylation of the 14-methyl group, resulting in its stepwise conversion into an alcohol, an aldehyde and then a carboxylate, which is removed as formic acid. Sterol 14-demethylase is an unusual cytochrome P450 enzyme in that it is found in a broad variety of organisms including ANIMALS; PLANTS; FUNGI; and protozoa.Dextromethorphan: Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.Potentiometry: Solution titration in which the end point is read from the electrode-potential variations with the concentrations of potential determining ions. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Oxazines: Six-membered heterocycles containing an oxygen and a nitrogen.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Cell Line, Tumor: A cell line derived from cultured tumor cells.Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called CATHODE RAYS.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Antimycin A: An antibiotic substance produced by Streptomyces species. It inhibits mitochondrial respiration and may deplete cellular levels of ATP. Antimycin A1 has been used as a fungicide, insecticide, and miticide. (From Merck Index, 12th ed)Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Electron Transport Chain Complex Proteins: A complex of enzymes and PROTON PUMPS located on the inner membrane of the MITOCHONDRIA and in bacterial membranes. The protein complex provides energy in the form of an electrochemical gradient, which may be used by either MITOCHONDRIAL PROTON-TRANSLOCATING ATPASES or BACTERIAL PROTON-TRANSLOCATING ATPASES.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Lauric Acids: 12-Carbon saturated monocarboxylic acids.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Spectrophotometry, Ultraviolet: Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Hemeproteins: Proteins that contain an iron-porphyrin, or heme, prosthetic group resembling that of hemoglobin. (From Lehninger, Principles of Biochemistry, 1982, p480)Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.7-Alkoxycoumarin O-Dealkylase: A drug-metabolizing enzyme found in the hepatic, placental and intestinal microsomes that metabolizes 7-alkoxycoumarin to 7-hydroxycoumarin. The enzyme is cytochrome P-450- dependent.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Cytochromes b6: Cytochromes of the b group that are found as components of the CYTOCHROME B6F COMPLEX. They contain two non-covalently bound HEME B groups.Tetramethylphenylenediamine: Used in the form of the hydrochloride as a reagent in ANALYTICAL CHEMISTRY TECHNIQUES.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
"In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil". Drug Metabolism and Disposition. 28 ( ... is an enzyme that in humans is encoded by the CYP2C9 gene. CYP2C9 is an important cytochrome P450 enzyme with a major role in ... "Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and ... "Inhibitory effect of medroxyprogesterone acetate on human liver cytochrome P450 enzymes". European Journal of Clinical ...
"Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells". The ... The first step of steroidogenesis is dependent on the transfer of electrons from NADPH to a P450 type enzyme (P450scc) via an ... "Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells ... His Ph.D. thesis was on the "Mechanism of electron transport to cytochrome P-450 in adrenal cortex mitochondrial steroid ...
"Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells" (PDF). ... The rapid actions of ACTH include stimulation of cholesterol delivery to the mitochondria where the P450scc enzyme is located. ... Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an ... The long term actions of ACTH include stimulation of the transcription of the genes coding for steroidogenic enzymes, ...
"Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells" (PDF). J ... and adrenodoxin that transfer 2 electrons from NADPH to the P450 for each monooxygenase reaction catalyzed by the enzyme. In ... This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that ... Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. ...
St John's wort has been shown to cause multiple drug interactions through induction of the cytochrome P450 enzymes CYP3A4 and ... This drug-metabolizing enzyme induction results in the increased metabolism of certain drugs, leading to decreased plasma ... Obach RS (2000). "Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in ... Song M, Hong M, Lee MY, Jee JG, Lee YM, Bae JS, Jeong TC, Lee S (2013). "Selective inhibition of the cytochrome P450 isoform by ...
... enzyme induction) or inhibited (enzyme inhibition). If drug A is metabolized by a cytochrome P450 enzyme and drug B inhibits or ... and the most important enzymes are CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. The majority of the enzymes are also ... If drug A is metabolized by a cytochrome P450 enzyme and drug B induces or increases the enzyme's activity, then blood plasma ... "cytochrome P450". Danielson PB (December 2002). "The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism ...
... and FMN-containing enzyme NADPH:cytochrome P450 reductase The general scheme of electron flow in the POR/P450 system is: NADPH ... In phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified ... in cases where an enzyme is responsible for metabolizing a pro-drug into a drug, enzyme induction can speed up this conversion ... P450 reductase, POR, CPR, CYPOR, is a membrane-bound enzyme required for electron transfer to cytochrome P450 in the microsome ...
Cytochrome P-450 enzyme induction and inhibition[38][39][40] Potent inducers. Potent inhibitors. Substrates ... known as cytochrome P-450, is the most important family of metabolizing enzymes in the liver. Cytochrome P-450 is the terminal ... Drugs interact with the enzyme family in several ways.[41] Drugs that modify cytochrome P-450 enzyme are referred to as either ... P-450 is cytochrome P-450 enzymes. 3 different pathways are depicted for Drugs A, B and C. ...
"Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells" (PDF). ... P450scc is a member of the cytochrome P450 superfamily of enzymes (family 11, subfamily A, polypeptide 1). The gene name is ... Steroidogenic enzyme Cytochrome P450 oxidase GRCh38: Ensembl release 89: ENSG00000140459 - Ensembl, May 2017 GRCm38: Ensembl ... "Expression of cytochrome P450 genes encoding enzymes active in the metabolism of tamoxifen in human uterine endometrium". ...
In fetuses, ethanol is instead metabolized at much slower rates by different enzymes from the cytochrome P-450 superfamily (CYP ... Exposure to ethanol is known to promote further induction of this enzyme in fetal and adult tissues. CYP2E1 is a major ... The enzyme encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a ... Thanks to enzymes in their gut, and particularly one called ADH4, they can make use of the calories in alcohol. The average ...
"Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells ... The enzyme functions as the first electron transfer protein of mitochondrial P450 systems such as P450scc. The FAD coenzyme ... Hanukoglu I (1996). "Electron transfer proteins of cytochrome P450 systems" (PDF). Adv. Mol. Cell Biol. 14: 29-55. doi:10.1016/ ... Hanukoglu I, Hanukoglu Z (May 1986). "Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase ...
Depending on the substrate and enzyme involved, P450 enzymes can catalyze any of a wide variety of reactions. A hypothetical ... enzyme induction) or by directly inhibiting the activity of the CYP (enzyme inhibition). This is a major source of adverse drug ... Cytochrome P450, B-class InterPro: IPR002397 Cytochrome P450, mitochondrial InterPro: IPR002399 Cytochrome P450, E-class, group ... Preissner S (2010). "Cytochrome P450 database". Nucleic Acids Research. Sim SC (2008-09-04). "Human Cytochrome P450 (CYP) ...
Detoxifying enzymes such as antioxidant and cytochrome P450 enzymes play a main role in aquatic organisms in the removal of ... It has been extensively studied and reported that induction of cytochrome P450 protein related ethoxyresorufin -O- deethylase ( ... Cytochrome P450-dependent monooxygenase system mediated hydrocarbon metabolism and antioxidant enzyme responses in prawn, ... Does Cytochrome P450 exists in Prawn? Macrobrachium malcolmsonii (Milne-Edwards, 1844) is an omnivorous bottom dwelling fresh ...
Cytochrome P450 oxidases (or P-450), a specific class of MFO, have been specifically connected to detoxification of plant ... Herbivores may also produce salivary enzymes that reduce the degree of defense generated by a host plant. The enzyme glucose ... The induction of P-450 after initial nicotine ingestion allowed the larval tobacco hornworms to increase feeding on the toxic ... Insect P450 enzymes. Annual Review of Entomology 44:507 - 533. Snyder, M. J., and J. I. Glendinning. 1996. Causal connection ...
A leading hypothesis is that PAHs may activate the cytochrome enzyme CYP1B1 in vascular smooth muscle cells. This enzyme then ... "Role of Aryl Hydrocarbon Receptor-mediated Induction of the CYP1 Enzymes in Environmental Toxicity and Cancer". Journal of ... Androutsopoulos, V.P.; Tsatsakis, A.M.; Spandidos, D.A. (2009). "Cytochrome P450 CYP1A1: wider roles in cancer progression and ... PAH exposure can increase production of the cytochrome enzymes, allowing the enzymes to convert PAHs into mutagenic diol ...
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which ... Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells". Neurosci. Lett. 314 (1-2): 45-8. doi:10.1016/ ... "Entrez Gene: CYP46A1 cytochrome P450, family 46, subfamily A, polypeptide 1". Human CYP46A1 genome location and CYP46A1 gene ... 2004). "Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain". ...
NADPH using enzymes). 7-ethoxyresorufin, is a compound used as the substrate in the measurement of cytochrome P450 (CYP1A1) ... Usually, in the presence of NADPH dehydrogenase or NADH dehydrogenase as the enzyme, NADPH or NADH is the reductant that ... induction using the ethoxyresorufin-O-deethylase (EROD) assay system in cell culture and environmental samples, produced in ... The compound is catalysed by the enzyme to produce the same fluorescent product, resorufin.[citation needed] 1,3-dichloro-7- ...
... with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochromes P450 2E1 and 3A4 convert approximately 5 ... This may be due to individual ("idiosyncratic") differences in the expression and activity of certain enzymes in one of the ... The concomitant use of the CYP2E1 inhibitor isoniazid increases the risk of hepatotoxicity, though whether 2E1 induction is ... and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of ...
... and has been found to induce several hepatic cytochrome P450 enzymes, such as CYP3A4, especially when concentrations are high, ... or induction of teratogenicity (i.e., virilization of female fetuses). Progesterone is a substrate for 5α-reductase and has ... been said to be a competitive inhibitor of this enzyme. 5α-Reductase is expressed in the skin, hair follicles, and prostate ... CYP17A1, the cytochrome P450 gene that encodes 17α-hydroxylase and 17,20-lyase, is expressed mainly in the gonads (ovaries and ...
Smoking has been shown to enhance the elimination rate of toluene from the body, perhaps as a result of enzyme induction. The ... The primary route of toluene metabolism is by hydroxylation to benzyl alcohol by members of the cytochrome P450 (CYP) ... Often toluene exposure occurs in conjunction with benzene and since they are to some degree metabolised by the same enzymes, ... "Human cytochrome P450 isoform specificity in the regioselective metabolism of toluene and o-, m- and p-xylene". Journal of ...
One of the primary targets of PXR activation is the induction of CYP3A4, an important phase I oxidative enzyme that is ... PXR is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter ... In addition, PXR up regulates the expression of phase II conjugating enzymes such as glutathione S-transferase and phase III ... Geick A, Eichelbaum M, Burk O (May 2001). "Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin ...
... reactions which are catalyzed by cytochrome P450 enzymes predominantly in the liver, but also in various other tissues. ... Induction of apoptosis by 2-meOE2 may be p53 dependent or independent. 2-meOE2 has also been found to inhibit aromatase ... The enzyme most responsible for estradiol 4-hydroxylation is CYP1B1. In humans, CYP1B1 mRNA and protein exhibit constitutive ... thereby confirming the involvement of cytochrome P450 enzymes in the blockade of tumor blood supply. Further antitumor activity ...
... converts to phenobarbital and PEMA;[67] it is still unknown which exact cytochrome P450 enzymes are responsible.[55] ... This enzyme induction occurs at therapeutic doses. In fact, people taking these drugs have displayed the highest degree of ... "Effects of Prototypical Microsomal Enzyme Inducers on Cytochrome P450 Expression in Cultured Human Hepatocytes". Drug ... The risk of fractures is higher for people taking enzyme-inducing anticonvulsants than for people taking non-enzyme-inducing ...
... converts to phenobarbital and PEMA; it is still unknown which exact cytochrome P450 enzymes are responsible. The ... This enzyme induction occurs at therapeutic doses. In fact, people taking these drugs have displayed the highest degree of ... "Effects of Prototypical Microsomal Enzyme Inducers on Cytochrome P450 Expression in Cultured Human Hepatocytes". Drug ... Desta, Zeruesenay; Nadia V. Soukhova; David A. Flockhart (February 2001). "Inhibition of Cytochrome P450 (CYP450) Isoforms by ...
Steroidogenesis, showing many of the enzyme activities that are performed by cytochrome P450 enzymes.[27] HSD: Hydroxysteroid ... enzyme induction) or by directly inhibiting the activity of the CYP (enzyme inhibition). This is a major source of adverse drug ... Wikimedia Commons has media related to Cytochrome P450.. *. Preissner S (2010). "Cytochrome P450 database". Nucleic Acids ... originally from Pseudomonas putida has been used as a model for many cytochromes P450 and was the first cytochrome P450 three- ...
The naming of enzymes by adding the suffix "-ase" to the substrate on which the enzyme acts, has been traced to French ... 사이토크롬 P450 산화효소가 있는데, 사이토크롬 P450 산화효소는 약물 대사에서 중요하다. 이러한 효소의 유도 또는 저해는 약물 상호작용을 일으킬 수 있다.[94] 또한 효소의 양은 효소의 분해 속도를 변화시킴으로써 조절할 ... Yoshikawa S, Caughey WS (May 1990). "Infrared evidence of cyanide binding to iron and copper sites in bovine heart cytochrome c ... Skett P, Gibson GG (2001). 》Chapter 3: Induction and Inhibition of Drug Metabolism》. 》Introduction to Drug Metabolism》 3판. ...
... of a cocktail of representative probe substrates of cytochrome P450 (CYP) enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 ... A Study to Evaluate the Effect of Ustekinumab on Cytochrome P450 Enzyme Activities Following Induction and Maintenance Dosing ... Drug Interaction Study to Evaluate the Effect of Ustekinumab on Cytochrome P450 Enzyme Activities Following Induction and ... Geometric Mean Ratio (Day 22/ Day 1) of the Maximum Plasma Concentration (Cmax) of Cytochrome P450 Probe Substrates (Midazolam ...
1999) Effect of cryopreservation on cytochrome P-450 enzyme induction in cultured rat hepatocytes. Drug Metab Dispos 27:327-335 ... 1995) Human cytochrome P450 enzymes. in Cytochrome P450. Structure, Mechanism and Biochemistry, ed Ortiz de Montellano PR ( ... Inhibition of Human Cytochromes P450.. The rates of metabolism of marker substrates for nine cytochrome P450 enzymes (Table 1) ... Induction of Human Cytochromes P450.. The ability of modafinil to induce cytochrome P450 activities was examined in vitro in ...
Mammalia atoms biological biosynthesis cell degradation enzyme enzymes food growth insects metabolism oxygen structure system ... Role of Cytochrome b5 in the NADH Synergism of NADPH-Dependent Reactions of the Cytochrome P-450 Monooxygenase System of ... Comparison of the Induction Course, Biophysical Chemical Interactions and Photochemical Action Spectra of Phenobarbital and 3- ... Role of Cytochrome b5 in NADPH- and NADH-Dependent Hydroxylation by the Reconstituted Cytochrome P-450- or P-448-Containing ...
Cytochrome P450 2B6 (CYP2B6) belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both ... Cytochrome P450 2B6 (CYP2B6) belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both ... 2010). Profiling induction of cytochrome p450 enzyme activity by statins using a new liquid chromatography-tandem mass ... Inhibition and induction of human cytochrome P450 enzymes: current status. Arch. Toxicol. 82, 667-715. ...
1990) Enzyme induction in the cytochrome P-450 system. Pharmacol Ther 45:241-298. ... and it has been suggested that this effect may be related to their ability to induce drug-metabolizing enzymes, particularly ... cytochrome P450. DHBG. 5-[(6,7-dihydroxy-6-keto-2-octenyl)oxy]psoralen. HBBS. Hanks balanced salt solution. HMF. 3,3′,4′,5,6,7 ... Polymethoxylated Flavones in Orange Juice Are Inhibitors of P-glycoprotein but Not Cytochrome P450 3A4. Hitomi Takanaga, Ayako ...
... indicating that they can activate some intracellular processes while not showing any effect on enzyme induction. The absence of ... In contrast, the induction of the enzymes and the mRNA by cAMP analogs or forskolin required the continuous presence of these ... Exposure of the cells to ACTH for 1-2 h was sufficient for maximal induction of the enzymes and P450scc mRNA. ... ability of a brief pulse of ACTH indicates that ACTH can rapidly initiate a series of reactions that result in enzyme induction ...
1990) Enzyme induction in the cytochrome P-450 system. Pharmacol Ther 45:241-298. ... Identification of ketene reactive intermediate of erlotinib possibly responsible for inactivation of P450 enzymes ... cytochrome P-450. AUC. area under the curve. Cmax. maximal plasma concentration. ... 1996) Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J ...
1998 Induction of Arabidopsis tryptophan pathway enzymes and camalexin by amino acid starvation, oxidative stress, and an ... We report here that the atr4 locus is the CYP83B1 cytochrome P450 gene. The CYP83B1 enzyme has been shown to catalyze the N- ... The highly related Arabidopsis cytochrome P450 enzymes CYP79B2 and CYP79B3 were recently shown to convert tryptophan to IAOx, a ... In this work we show that loss-of-function alleles in the cytochrome P450 gene CYP83B1 are atr mutants of the atr4 ...
2010) Profiling induction of cytochrome p450 enzyme activity by statins using a new liquid chromatography-tandem mass ... 2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic ... 2008) Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 82:667-715. ... Measurement of P450 Enzyme Activities. P450 enzyme activities were determined in culture supernatants using a liquid ...
Cimetidine: Cimetidine inhibits many cytochrome P450 (oxidative) enzymes. In a study where PAXIL (30 mg once daily) was dosed ... The metabolism and pharmacokinetics of paroxetine may be affected by the induction or inhibition of drug-metabolizing enzymes. ... Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose ... Phenobarbital: Phenobarbital induces many cytochrome P450 (oxidative) enzymes. When a single oral 30-mg dose of PAXIL was ...
Drugs that are Metabolized by and/or Inhibit Cytochrome P450 Enzymes CYP Enzyme Inducers (these studies used both drugs at ... Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if ... CYP Enzyme Inhibitors Cimetidine: In healthy male patients (n=12), when cimetidine, a weak inhibitor of CYP1A2, CYP2D6, and ... In vitro data from human liver microsomes indicate that cytochrome 2D6 and 1A2 are involved in the formation of the 8-hydroxy ...
The principal methods used for the assessment of enzyme induction and enzyme inhibition are measurement of the pharmacokinetics ... which are endogenous substrates for cytochrome P450 IIIA enzymes, provides a non-invasive means of assessing enzyme induction ... Assessment of enzyme induction and enzyme inhibition in humans: toxicological implications Xenobiotica. 1990 Nov;20(11):1171-85 ... 1. The principal methods used for the assessment of enzyme induction and enzyme inhibition are measurement of the ...
Terriere LC: Enzyme induction, gene amplification and insect resistance to insecticides. In: Pest Resistance to Pesticides. ... P-450 = rnicrosornal cytochrome P-450; P-4501,~= cytochrome P-4501,~P-450,+ = cytochrorne P-45Q4 PEG = polyethyleneglycol 8000 ... Plenum Press, New York, pp 175205 (1983). 2. Terriere LC: Induction of detoxication enzymes in insects. Annu Rev Entomol 29, 71 ... Pestic Biochem Physiol35, 1(1989). 9. Guengerich FP: Enzymology of rat liver cytochromes P-450. In: Mammalian Cytochromes P-450 ...
Drugs that are Metabolized by and/or Inhibit Cytochrome P450 Enzymes. CYP Enzyme Inducers (these studies used both drugs at ... Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if ... CYP Enzyme Inhibitors Cimetidine: In healthy male patients (n=12), when cimetidine, a weak inhibitor of CYP1A2, CYP2D6, and ... In vitro data from human liver microsomes indicate that cytochrome 2D6 and 1A2 are involved in the formation of the 8-hydroxy ...
Inhibition and induction of human cytochrome P450 enzymes: current status. Olavi Pelkonen Pelkonen, Miia Turpeinen, +3 authors ... Characterization of chicken cytochrome P450 1A4 and 1A5: inter-paralog comparisons of substrate preference and inhibitor ... Drug metabolism enzymes in a steatotic model of rat treated with a high fat diet and a low dose of streptozotocin.. Andrea ... Enzyme-kinetic and immunochemical characteristics of mouse cDNA-expressed, microsomal, and purified CYP1A1 and CYP1A2.. @ ...
Johns wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003;290:1500-4.. View abstract. ... Inhibition of human cytochrome P450 enzymes by constituents of St. Johns wort, an herbal preparation used in the treatment of ... Induction and inhibition of cytochromes P450 by the St. Johns wort constituent hyperforin in human hepatocyte cultures. Drug ... Dresser, G. K., Schwarz, U. I., Wilkinson, G. R., and Kim, R. B. Coordinate induction of both cytochrome P4503A and MDR1 by St ...
"Effect of St Johns Wort on Drug Metabolism by Induction of Cytochrome P450 3A4 Enzyme." Journal of the American Medical ... As narcotics are used, the liver produces more and more of these enzymes, so that a dose of pain medication is removed from the ... The need for larger and more frequent doses is due to enzyme induction, in which narcotics are metabolized by the liver and ... The metabolism of narcotics relies on enzymes that are produced by the liver. ...
"Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells" (PDF). ... The rapid actions of ACTH include stimulation of cholesterol delivery to the mitochondria where the P450scc enzyme is located. ... Postorgasmic illness syndrome (POIS), through production of tyrosine hydroxylase and dopamine β-hydroxylase, which two enzymes ... The long term actions of ACTH include stimulation of the transcription of the genes coding for steroidogenic enzymes, ...
Cytochrome P-450 enzyme induction and inhibition[38][39][40] Potent inducers. Potent inhibitors. Substrates ... known as cytochrome P-450, is the most important family of metabolizing enzymes in the liver. Cytochrome P-450 is the terminal ... Drugs interact with the enzyme family in several ways.[41] Drugs that modify cytochrome P-450 enzyme are referred to as either ... P-450 is cytochrome P-450 enzymes. 3 different pathways are depicted for Drugs A, B and C. ...
The cytochrome P450 family of enzymes, the P-glycoprotein drug transporter, and their mechanisms for inhibition, induction, and ... Zanger UM, Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and ... Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 82(10):667-715PubMedCrossRefGoogle ... Stringer RA, Strain-Damerell C, Nicklin P, Houston JB (2009) Evaluation of recombinant cytochrome P450 enzymes as an in vitro ...
Keywords: cell transformation; cytochrome P450; Ah-receptor; enzyme induction Halogenated pyruvate derivatives as substrates of ... Prokaryotic enzymes formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease VIII (Nei) and their eukaryotic homologs NEIL1, ... whereas in F27 cells the induction was observed throughout the experiment. Induction levels of mRNA of the induction-regulating ... The ability to induce Ah-receptor-dependent genes encoding cytochrome P450 isoforms, Ah-receptor repressor, and NADPH-quinine ...
Presentation] Induction of cytochrome P450 3A enzymes by thalidomide in human hepatic cells2012. *. Author(s). Norie Murayama, ... Journal Article] Binding of Diverse Environmental Chemicals with Human Cytochromes P450 2A13, 2A6, and 1B1 and Enzyme ... Presentation] Roles of Auto-Induction of Human P450 3A Enzymes Involved in The Teratogenicity of Thalidomide2014. *. Author(s) ... Journal Article] Human HepaRG Cells can be Cultured in Hanging-Drop Plates for Cytochrome P450 Induction and Function Assays. ...
6: Depending on the substrate and enzyme involved, P450 enzymes can catalyse any of a wide variety of reactions. A hypothetical ... Many drugs may increase or decrease the activity of various CYP isozymes in a phenomenon known as enzyme induction and ... de:Cytochrom P450 it:Citocromo P450 nl:Cytochroom P450 no:Cytokrom P450 sv:Cytokrom P450 ... "cytochrome P450". Compendium of Chemical Terminology Internet edition. Danielson P (2002). "The cytochrome P450 superfamily: ...
Cytochrome P450 is a "superfamily" of enzymes that are the terminal oxidases of this oxidation system. "Cytochrome" means ... resulting in either reduced activity of the enzyme or increased activity of the enzyme referred to as enzyme induction (see " ... These enzymes contain iron and give the liver its red color. The name "P450" comes from the observation that the enzyme absorbs ... Medications metabolized by CYP3A4 or CYP2C9 are particularly susceptible to enzyme induction. Drugs known as "enzyme inducers" ...
Interindividual Variability in Inhibition and Induction of Cytochrome P450 Enzymes. Annu Rev Pharmacol Toxicol 2001; 41:535-567 ... I. Enzyme distribution and species specificity. Biochem Pharmacol 1965; 14:1405-1416.PubMedCrossRefGoogle Scholar ... Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich P. Interindividual Variations in Human Liver Cytochrome P-450 Enzymes ... Villeneuve J-P and Pichette V. Cytochrome P450 and Liver Diseases. Curr Drug Metab 2004; 5:273-282PubMedCrossRefGoogle Scholar ...
  • lmmunoinhibition of ECOD activity with anti-P-4501p, antiserum suggests that PB treatment in S house flies induced P-4501,,, and other forms of cytochromes P-450 with high activity toward this substrate. (docme.ru)
  • However, some gene or enzyme names for CYPs may differ from this nomenclature, denoting the catalytic activity and the name of the compound used as substrate. (wikidoc.org)
  • 1: The substrate binds to the active site of the enzyme, in close proximity to the heme group, on the side opposite to the peptide chain. (wikidoc.org)
  • A drug that is metabolized by a particular isoenzyme is a substrate for that enzyme. (podiatrytoday.com)
  • However, recent studies have shown that the P450 form can sometimes be recovered from P420 by the addition of substrate or alteration of pH [ 8 - 10 ]. (biochemsoctrans.org)
  • Report detailing methodology, donor demographics, mRNA levels, fold induction relative to vehicle control, concentration of metabolite of probe substrate, E max , EC 50 and F2 (concentration which leads to a 2-fold increase above E min ) if appropriate. (cyprotex.com)
  • The plasma concentrations of mirtzapine in patients are influenced by many factors, such as polymorphic cytochrome P450 enzymes contributing to its transformation to the metabolites.The aim of this study was to investigate the determinant factors for individual variations of metabolic clearance of mirtazapine using in vitro and in vivo methods. (nii.ac.jp)
  • Thapliyal and Maru [ 14 ] reported curcumins inhibited the activity of cytochrome P450 in vitro and in vivo. (hindawi.com)
  • Fluvoxamine-theophylline interaction: rip between in vitro and in vivo constraint constants toward cytochrome P4501A2. (nippon-kan.org)
  • Genes encoding tryptophan pathway enzymes are transcriptionally induced by a variety of stress signals, presumably to increase the production of both tryptophan and secondary metabolites during defense responses. (genetics.org)
  • To understand the mechanism of transcriptional induction, we isolated altered tryptophan regulation ( atr ) mutants in Arabidopsis thaliana with activated transcription of tryptophan genes. (genetics.org)
  • Genes encoding CYP enzymes, and the enzymes themselves, are designated with the abbreviation "CYP", followed by an Arabic numeral indicating the gene family, a capital letter indicating the subfamily, and another numeral for the individual gene. (wikidoc.org)
  • Receptor-dependent transcriptional activa- tion of cytochrome P4503A genes: induction mechanisms, species differences and interindividual varying in geezer. (nippon-kan.org)
  • This induction can have implications in a variety of contexts, particularly during the study of the pharmacokinetics, pharmacodynamics, and drug-drug interaction profile of a candidate therapeutic compound. (mcponline.org)
  • The name cytochrome P450 is derived from the fact that these are colored ('chrome') cellular ('cyto') proteins, with a "pigment at 450 nm", so named for the characteristic Soret peak formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (often with sodium dithionite ) and complexed to carbon monoxide . (wikidoc.org)
  • The name "P450" comes from the observation that the enzyme absorbs a very characteristic wavelength (450 nm) of ultraviolet light when it is exposed to carbon monoxide. (podiatrytoday.com)
  • The conclusion from this study was that ethoxyresorufin O -deethylase [cytochrome P450 (CYP) 2 1A] and nifedipine oxidase (CYP3A) activities were slightly induced by modafinil, which also increased the activity of dextromethorphan demethylase (CYP2D6) at the highest concentration tested (1000 μM). (aspetjournals.org)
  • However, it is proportionally more important in intestinal tissue and is the primary CYP3A enzyme in the kidney. (podiatrytoday.com)
  • NR1I3) have been shown to play crucial roles in induction of members of the CYP3A and CYP2B subfamilies in human and mouse liver, respectively (reviewed in refs. (pnas.org)
  • They found that all three species inhibit several of these enzymes. (eurekalert.org)
  • Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. (drugbank.ca)
  • Geranylgeranyl pyrophosphate (GGPP) and geranylgeraniol (GGOH) are used for the prenylation of GTP binding proteins and can reverse the antiresorptive action of nitrogen-containing bisphosphonates which inhibit farnesyl pyrophosphate synthase, an enzyme of the mevalonate pathway involved in the formation of GGPP. (biomedsearch.com)
  • Dr. Scatina's research interests include identification of metabolites, metabolicpathways and enzymes responsible, in vitro-in vivo extrapolation, and prediction of druginteractions. (whsmith.co.uk)
  • The aim of this study was to reveal possible modulating effects of consumption of Brussels sprouts on duodenal, rectal and lymphocytic (i) glutathione S-transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) glutathione (GSH) content. (tudelft.nl)
  • The sections in this chapter of other health outcomes include chloracne, porphyria cutanea tarda, other metabolic and digestive disorders (diabetes mellitus, alterations in hepatic enzymes, lipid abnormalities, and gastrointestinal ulcers), immune system disorders (immune modulation, autoimmunity), and a number of circulatory and respiratory disorders. (nap.edu)
  • But, these agents stimulated cortisol secretion to the medium quickly, indicating that they can activate some intracellular processes while not showing any effect on enzyme induction. (zenodo.org)
  • Avasimibe did not affect sterol 27-hydroxylase and oxysterol 7α-hydroxylase, 2 enzymes in the alternative pathway in bile acid synthesis. (tudelft.nl)
  • 11 This capability is important in defining the functional contribution of either enzyme pathway as the products of these pathways frequently have opposing effects on the circulation. (bmj.com)
  • Any patient currently taking TROG and with stable liver function assessed by liver enzymes (alanine and aspartate aminotransferase) was eligible to participate. (diabetesjournals.org)
  • These measures were repeated after 4 months of randomized therapy with either PIO or ROSI and included liver enzymes (alanine and aspartate aminotransferase), HbA 1c , and fasting plasma lipids (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides). (diabetesjournals.org)
  • Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase , which leads to an increase in intracellular cAMP and subsequent activation of protein kinase A . (wikipedia.org)
  • The iron is tethered to the P450 protein via a thiolate ligand derived from a cysteine residue. (wikidoc.org)