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 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.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.Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.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.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.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.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.Cytochrome b Group: Cytochromes (electron-transporting proteins) with protoheme (HEME B) as the prosthetic group.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.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.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 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.Nitrate Reductases: Oxidoreductases that are specific for the reduction of NITRATES.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.Cytochrome ReductasesCytochrome-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.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)Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.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).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.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)Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Ribonucleotide ReductasesNitrite Reductases: A group of enzymes that oxidize diverse nitrogenous substances to yield nitrite. (Enzyme Nomenclature, 1992) EC 1.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.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.Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.Ferredoxin-NADP Reductase: An enzyme that catalyzes the oxidation and reduction of FERREDOXIN or ADRENODOXIN in the presence of NADP. EC 1.18.1.2 was formerly listed as EC 1.6.7.1 and EC 1.6.99.4.FMN Reductase: An enzyme that utilizes NADH or NADPH to reduce FLAVINS. It is involved in a number of biological processes that require reduced flavin for their functions such as bacterial bioluminescence. Formerly listed as EC 1.6.8.1 and EC 1.5.1.29.Kinetics: The rate dynamics in chemical or physical systems.Glutathione Reductase: Catalyzes the oxidation of GLUTATHIONE to GLUTATHIONE DISULFIDE in the presence of NADP+. Deficiency in the enzyme is associated with HEMOLYTIC ANEMIA. Formerly listed as EC 1.6.4.2.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)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.Thioredoxin-Disulfide Reductase: A FLAVOPROTEIN enzyme that catalyzes the oxidation of THIOREDOXINS to thioredoxin disulfide in the presence of NADP+. It was formerly listed as EC 1.6.4.5Oxidoreductases, N-DemethylatingMolecular 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.Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.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.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.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.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.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)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.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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.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)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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.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.Quinone Reductases: NAD(P)H:(quinone acceptor) oxidoreductases. A family that includes three enzymes which are distinguished by their sensitivity to various inhibitors. EC 1.6.99.2 (NAD(P)H DEHYDROGENASE (QUINONE);) is a flavoprotein which reduces various quinones in the presence of NADH or NADPH and is inhibited by dicoumarol. EC 1.6.99.5 (NADH dehydrogenase (quinone)) requires NADH, is inhibited by AMP and 2,4-dinitrophenol but not by dicoumarol or folic acid derivatives. EC 1.6.99.6 (NADPH dehydrogenase (quinone)) requires NADPH and is inhibited by dicoumarol and folic acid derivatives but not by 2,4-dinitrophenol.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)Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Tetrahydrofolate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.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.Dealkylation: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)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.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.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.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.Methylenetetrahydrofolate Reductase (NADPH2): A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 1.1.1.171.RNA, 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.Nitrate Reductase (NADH): An NAD-dependent enzyme that catalyzes the oxidation of nitrite to nitrate. It is a FLAVOPROTEIN that contains IRON and MOLYBDENUM and is involved in the first step of nitrate assimilation in PLANTS; FUNGI; and BACTERIA. It was formerly classified as EC 1.6.6.1.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Alcohol Oxidoreductases: A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.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.Hydroxymethylglutaryl-CoA Reductase Inhibitors: Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.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)Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.beta-Naphthoflavone: A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)Methionine Sulfoxide Reductases: Reductases that catalyze the reaction of peptide-L-methionine -S-oxide + thioredoxin to produce peptide-L-methionine + thioredoxin disulfide + H(2)O.Oxidoreductases Acting on CH-CH Group Donors: A subclass of enzymes which includes all dehydrogenases acting on carbon-carbon bonds. This enzyme group includes all the enzymes that introduce double bonds into substrates by direct dehydrogenation of carbon-carbon single bonds.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.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.Oxygenases: Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1.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.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.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.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.Sulfaphenazole: A sulfonilamide anti-infective agent.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Dihydropteridine Reductase: An enzyme that catalyzes the reduction of 6,7-dihydropteridine to 5,6,7,8-tetrahydropteridine in the presence of NADP+. Defects in the enzyme are a cause of PHENYLKETONURIA II. Formerly listed as EC 1.6.99.7.Proadifen: An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.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.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)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).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.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)Troleandomycin: A macrolide antibiotic that is similar to ERYTHROMYCIN.Dithionite: Dithionite. The dithionous acid ion and its salts.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)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.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.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.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.Methylcholanthrene: A carcinogen that is often used in experimental cancer studies.Thioredoxin Reductase 1: A subtype of thioredoxin reductase found primarily in the CYTOSOL.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.Ferricyanides: Inorganic salts of the hypothetical acid, H3Fe(CN)6.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.Enoyl-(Acyl-Carrier-Protein) Reductase (NADH): An NAD-dependent enzyme that catalyzes the oxidation of acyl-[acyl-carrier protein] to trans-2,3-dehydroacyl-[acyl-carrier protein]. It has a preference for acyl groups with a carbon chain length between 4 to 16.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.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.Ferredoxins: Iron-containing proteins that transfer electrons, usually at a low potential, to flavoproteins; the iron is not present as in heme. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.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.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.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.Cytochromes c6: Cytochromes of the c type that are involved in the transfer of electrons from CYTOCHROME B6F COMPLEX and PHOTOSYSTEM I.Bacterial Proteins: Proteins found in any species of bacterium.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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Flavin-Adenine Dinucleotide: A condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972)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.Paracoccus denitrificans: A species of bacteria isolated from soil.Oxidoreductases Acting on Sulfur Group Donors: Oxidoreductases with specificity for oxidation or reduction of SULFUR COMPOUNDS.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.Flavin Mononucleotide: A coenzyme for a number of oxidative enzymes including NADH DEHYDROGENASE. It is the principal form in which RIBOFLAVIN is found in cells and tissues.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.NAD: A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)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.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.Flavins: Derivatives of the dimethylisoalloxazine (7,8-dimethylbenzo[g]pteridine-2,4(3H,10H)-dione) skeleton. Flavin derivatives serve an electron transfer function as ENZYME COFACTORS in FLAVOPROTEINS.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)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.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.Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.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)Succinate Cytochrome c Oxidoreductase: An electron transport chain complex that catalyzes the transfer of electrons from SUCCINATE to CYTOCHROME C. It includes ELECTRON TRANSPORT COMPLEX II and ELECTRON TRANSPORT COMPLEX III.Biocatalysis: The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.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.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.Iron-Sulfur Proteins: A group of proteins possessing only the iron-sulfur complex as the prosthetic group. These proteins participate in all major pathways of electron transport: photosynthesis, respiration, hydroxylation and bacterial hydrogen and nitrogen fixation.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.Oxazines: Six-membered heterocycles containing an oxygen and a nitrogen.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Mevalonic AcidSteroid 21-Hydroxylase: An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Anaerobiosis: The complete absence, or (loosely) the paucity, of gaseous or dissolved elemental oxygen in a given place or environment. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)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.Arsenate Reductases: Oxidoreductases that specifically reduce arsenate ion to arsenite ion. Reduction of arsenate is a critical step for its biotransformation into a form that can be transported by ARSENITE TRANSPORTING ATPASES or complexed by specific sulfhydryl-containing proteins for the purpose of detoxification (METABOLIC DETOXIFICATION, DRUG). Arsenate reductases require reducing equivalents such as GLUTAREDOXIN or AZURIN.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.Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Molecular Weight: The sum of the weight of all the atoms in a molecule.Ubiquinone: A lipid-soluble benzoquinone which is involved in ELECTRON TRANSPORT in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals.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.NADH Dehydrogenase: A flavoprotein and iron sulfur-containing oxidoreductase that catalyzes the oxidation of NADH to NAD. In eukaryotes the enzyme can be found as a component of mitochondrial electron transport complex I. Under experimental conditions the enzyme can use CYTOCHROME C GROUP as the reducing cofactor. The enzyme was formerly listed as EC 1.6.2.1.Lauric Acids: 12-Carbon saturated monocarboxylic acids.Cholestanetriol 26-Monooxygenase: An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol.3-Oxoacyl-(Acyl-Carrier-Protein) Reductase: A 3-oxoacyl reductase that has specificity for ACYL CARRIER PROTEIN-derived FATTY ACIDS.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.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.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.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.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.Succinate Dehydrogenase: A flavoprotein containing oxidoreductase that catalyzes the dehydrogenation of SUCCINATE to fumarate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II.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.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.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.Vitamin K Epoxide Reductases: OXIDOREDUCTASES which mediate vitamin K metabolism by converting inactive vitamin K 2,3-epoxide to active vitamin K.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.Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.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.Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Hemeproteins: Proteins that contain an iron-porphyrin, or heme, prosthetic group resembling that of hemoglobin. (From Lehninger, Principles of Biochemistry, 1982, p480)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)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.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.Aerobiosis: Life or metabolic reactions occurring in an environment containing oxygen.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.Dinitrogenase Reductase: A non-heme iron-sulfur protein isolated from Clostridium pasteurianum and other bacteria. It is a component of NITROGENASE along with molybdoferredoxin and is active in nitrogen fixation.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.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)Thioredoxins: Hydrogen-donating proteins that participates in a variety of biochemical reactions including ribonucleotide reduction and reduction of PEROXIREDOXINS. Thioredoxin is oxidized from a dithiol to a disulfide when acting as a reducing cofactor. The disulfide form is then reduced by NADPH in a reaction catalyzed by THIOREDOXIN REDUCTASE.Metabolic Detoxication, Phase I: Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Receptors, Steroid: Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.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.Sugar Alcohol Dehydrogenases: Reversibly catalyzes the oxidation of a hydroxyl group of sugar alcohols to form a keto sugar, aldehyde or lactone. Any acceptor except molecular oxygen is permitted. Includes EC 1.1.1.; EC 1.1.2. and EC 1.1.99.Hydroxytestosterones: 17 beta-Hydroxy-4-androsten-3-ones. Testosterone derivatives formed by the substitution of one or more hydroxyl groups in any position.
CYP2D6 a member of the cytochrome P450 mixed oxidase system. "Hydroxyurea". The American Society of Health-System Pharmacists. ... Hydroxycarbamide decreases the production of deoxyribonucleotides via inhibition of the enzyme ribonucleotide reductase by ... Cytochrome P-450 CYP2D6 Inhibitors - Acts as an inhibitor to one of the most important enzymes involved in the metabolism of ... Hydroxyurea selectively inhibits ribonucleoside diphosphate reductase, an enzyme required to convert ribonucleoside ...
... are the Cytochrome P450 (CYP) enzymes. The term Cytochrome P450 was coined by Omura and Sato in 1962 to describe the membrane- ... For example, CYP2D6 refers to family 2, subfamily D, and gene number 6. From a clinical perspective, the most commonly tested ... The vitamin K epoxide reductase complex subunit 1 (VKORC1) is responsible for the pharmacodynamics of warfarin. VKORC1 along ... "Genetic polymorphisms in cytochrome P450 oxidoreductase influence microsomal P450-catalyzed drug metabolism". Pharmacogenet ...
"Effects of genetic variants of human P450 oxidoreductase on catalysis by CYP2D6 in vitro". Pharmacogenetics and Genomics. 20 ( ... P450 reductase, POR, CPR, CYPOR) is a membrane-bound enzyme required for electron transfer from NADPH to cytochrome P450 in the ... Cytochrome P450 Reductase at the US National Library of Medicine Medical Subject Headings (MeSH) GeneReviews/NCBI/NIH/UW entry ... Cytochrome P450 reductase (EC 1.6.2.4; also known as NADPH:ferrihemoprotein oxidoreductase, NADPH:hemoprotein oxidoreductase, ...
A second electron is transferred, from either cytochrome P450 reductase, ferredoxins, or cytochrome b5, reducing the Fe-O2 ... CYP2D6, and CYP3A4). A subset of cytochrome P450 enzymes play important roles in the synthesis of steroid hormones ( ... Cytochrome P450, B-class InterPro: IPR002397 Cytochrome P450, mitochondrial InterPro: IPR002399 Cytochrome P450, E-class, group ... Substrate binding induces electron transfer from NAD(P)H via cytochrome P450 reductase or another associated reductase. ...
... cytochrome reductases MeSH D08.811.682.608.191.237 --- cytochrome-b(5) reductase MeSH D08.811.682.608.191.500 --- nadph- ... cytochrome p-450 cyp1a1 MeSH D08.244.453.040.777 --- cytochrome p-450 cyp1a2 MeSH D08.244.453.040.888 --- cytochrome p-450 ... cytochromes c1 MeSH D08.244.286.300 --- cytochromes c2 MeSH D08.244.286.600 --- cytochromes c6 MeSH D08.244.453.040 --- aryl ... cytochrome b6f complex MeSH D08.811.600.710.374.500 --- cytochromes b6 MeSH D08.811.600.710.374.750 --- cytochromes f MeSH ...
... cytochrome p-450 cyp2e1 MeSH D12.776.422.220.453.040.972 - cytochrome p-450 cyp3a MeSH D12.776.422.220.453.085 - camphor 5- ... nitrate reductase (nad(p)h) MeSH D12.776.556.579.374.375.988 - nitrate reductase (nadph) MeSH D12.776.556.579.374.450 - ... cytochromes a MeSH D12.776.422.220.175.500 - cytochromes a1 MeSH D12.776.422.220.175.600 - cytochromes a3 MeSH D12.776.422.220. ... cytochromes b MeSH D12.776.422.220.187.500 - cytochromes b5 MeSH D12.776.422.220.286.100 - cytochromes c MeSH D12.776.422.220. ...
Guengerich FP, Johnson WW (December 1997). "Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: ... Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19". Clinical Pharmacokinetics. 29 (3): 192-209. doi:10.2165/ ... Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme. This protein, a member of the cytochrome P450 mixed-function oxidase ... "Cytochrome P450 2C19 (CYP2C19) Genotype". Mayo Medical Laboratories. June 2013. "Entrez Gene: CYP2C19 cytochrome P450, family 2 ...
Microsomal P450 systems, in which electrons are transferred from NADPH via cytochrome P450 reductase (variously CPR, POR, or ... CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP2R1, CYP2S1, CYP2U1, ... A second electron is transferred, from either cytochrome P450 reductase, ferredoxins, or cytochrome b5, reducing the Fe-O2 ... Substrate binding induces electron transfer from NAD(P)H via cytochrome P450 reductase or another associated reductase.[11] ...
Zhou S (6 April 2016). Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism. CRC Press. pp. 242-. ISBN 978-1- ... testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, respectively.[1][ ... and CYP2D6.[151] 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations.[151] The 6β- ... Zuber MX, Simpson ER, Waterman MR (Dec 1986). "Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in ...
The reduction of dolasetron to hydrodolasetron is mediated by a ubiquitous enzyme, carbonyl reductase. Cytochrome P-450 (CYP) ... In this study, mice (CD-1) were treated orally with dolasetron mesylate 75, 150, or 300 mg/kg/day (225, 450 or 900 mg/m²/day). ...
... with P450 reductase/cytochrome b5, CYP2C19 with P450 reductase/cytochrome b5, CYP2D6*1 with P450 reductase, CYP3A4 with P450 ... CYP2C19 with P450 reductase/cytochrome b5, CYP2D6*1 with P450 reductase, and CYP3A4 with P450 reductase/cytochrome b5. The ... Baculovirus cDNA-expressed isoenzymes (Supersomes) of CYP1A2 with P450 reductase, CYP2C8 with P450 reductase/cytochrome b5, ... Incubations without NADPH and with cytochrome P450 reductase/b5 without P450 enzymes served to exclude nonenzymatic metabolite ...
In both cases, tyramine is converted into DA by the cytochrome p-450 CYP2D6 isoform (EC: 1.14.14.1; CYP2, CYP2D genes) [140, ... T. Hiroi, S. Imaoka, and Y. Funae, "Dopamine formation from tyramine by CYP2D6," Biochemical and Biophysical Research ... and aldehyde reductases (ARs) (EC: 1.1.1.21; gene type AKR). ... "Cytochrome P450 mediates dopamine formation in the brain in ... cytochromes, oxidases, and oxygenases can also oxidize DA. For instance, prostaglandin H synthase (COX) (EC: 1.14.99.1) ...
Genome-wide microarray-based transcriptional profiling and qRT-PCR revealed that the cytochrome P450 gene CYP6M7 is responsible ... Functional co-expression of CYP2D6 and human NADPH-cytochrome P450 reductase in Escherichia coli. Pharmacogenetics. 1998, 8 (1 ... gambiae cytochrome P450 reductase, pACYC-AgCPR [28]. The expression of each gene, membrane isolation and P450 content were ... P450 concentration [31] and CPR activity by monitoring cytochrome c reduction [32]. The histidine-tagged An. gambiae cytochrome ...
CYP2D6 a member of the cytochrome P450 mixed oxidase system. "Hydroxyurea". The American Society of Health-System Pharmacists. ... Hydroxycarbamide decreases the production of deoxyribonucleotides via inhibition of the enzyme ribonucleotide reductase by ... Cytochrome P-450 CYP2D6 Inhibitors - Acts as an inhibitor to one of the most important enzymes involved in the metabolism of ... Hydroxyurea selectively inhibits ribonucleoside diphosphate reductase, an enzyme required to convert ribonucleoside ...
1996) In vitro interaction of the antipsychotic agent olanzapine with human cytochromes P450 CYP2C9, CYP2C19, CYP2D6, and CYP3A ... Studies were performed to determine the cytochromes P450 (P450) responsible for the biotransformation of (S)-13[(dimethylamino) ... The Interactions of a Selective Protein Kinase C Beta Inhibitor with the Human Cytochromes P450. Barbara J. Ring, Jennifer S. ... The Interactions of a Selective Protein Kinase C Beta Inhibitor with the Human Cytochromes P450. Barbara J. Ring, Jennifer S. ...
... are the Cytochrome P450 (CYP) enzymes. The term Cytochrome P450 was coined by Omura and Sato in 1962 to describe the membrane- ... For example, CYP2D6 refers to family 2, subfamily D, and gene number 6. From a clinical perspective, the most commonly tested ... The vitamin K epoxide reductase complex subunit 1 (VKORC1) is responsible for the pharmacodynamics of warfarin. VKORC1 along ... "Genetic polymorphisms in cytochrome P450 oxidoreductase influence microsomal P450-catalyzed drug metabolism". Pharmacogenet ...
Cytochrome P-450 CYP2C9 / genetics Actions. * Search in PubMed * Search in MeSH ... CYP2D6 with tramadol (318 544 veterans [4.1%]), and CYP2C9 or VKORC1 with warfarin (7 163 349 veterans [92.2%]). ... Vitamin K Epoxide Reductases / genetics Actions. * Search in PubMed * Search in MeSH ... variants and phenoconversion in 5408 Australian patients genotyped for CYP2D6, CYP2C19, CYP2C9 and VKORC1 genes. Mostafa S, ...
P450 reductase, CYP2A6 + P450 reductase, CYP2C9-Arg 144 + P450 reductase, CYP2C19 + P450 reductase, CYP2D6-Val 374 + P450 ... P450 metabolism. The metabolism of compounds of the invention through the main isoforms of the human cytochrome system P450 are ... Incubates contain a fixed concentration of cytochrome P450 (eg 50 pmoles) and are conducted over 1 hour. The involvement of a ... the presence of supersomes ovenexpressing various cytochrome P450 isoforms, including CYP1A2 + ...
Cytochrome P-450 CYP2D6. *Cytochrome P-450 CYP3A. *Cytochrome P-450 Enzyme System ... Hydroxymethylglutaryl-CoA Reductase Inhibitors*Hydroxymethylglutaryl-CoA Reductase Inhibitors. *Hydroxymethylglutaryl CoA ... "Hydroxymethylglutaryl-CoA Reductase Inhibitors" is a descriptor in the National Library of Medicines controlled vocabulary ... This graph shows the total number of publications written about "Hydroxymethylglutaryl-CoA Reductase Inhibitors" by people in ...
6A); to endoxifen by CYP2D6 (Fig. 6B); and to N-didesmethyl-TAM by CYP2D6 (Fig. 6C), with participation of CYP3A4, CYP3A5, ... with reductase) were purchased from BD Biosciences (Franklin Lakes, NJ). Some HLMs were prepared from human liver tissues that ... ABBREVIATIONS: TAM, tamoxifen; ER, estrogen receptor; endoxifen, 4-hydroxy-N-desmethyl-tamoxifen; P450, cytochrome P450; HPLC, ... Jacolot F, Simon I, Dreano Y, Beaune P, Riche C, and Berthou F (1991) Identification of the cytochrome P450 IIIA family as the ...
Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase J. Biol. Chem. ... Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19 Clin. Pharmacokinet. 29:192-209 (1995).PubMedCrossRefGoogle ... Substrate oxidation by cytochrome P450 enzymes. In P. R. O. d. Montellano (ed.), Cytochrome P450: Structure, Mechanisms, and ... Impact of parallel pathways of drug elimination and multiple cytochrome P450 involvement on drug-drug interactions: CYP2D6 ...
In a similar approach, the genes encoding CYP2D6, CYP3A4, human cytochrome P450 reductase (hCPR) and Y. lipolytica cytochrome ... Human liver cytochromes P450 2D6 and 3A4 and human cytochrome P450 reductase (hCPR) as well as Y. lipolytica cytochrome P450 ... NADPH cytochrome c reductase (NCR) activity. The cytochrome P450 reductase-catalysed reduction of bovine heart cytochrome c was ... lipolytica together with human cytochrome P450 reductase (hCPR) or Y. lipolytica cytochrome P450 reductase (YlCPR). These whole ...
Fingerprint Dive into the research topics where Ichiro Ieiri is active. These topic labels come from the works of this person. Together they form a unique fingerprint. ...
Tam metabolism by CYP2D6 coexpressed with P450 reductase in a baculovirus infected insect cell line ("supersomes") exhibited ... Cytochrome P450 (P450) 3A4, the major catalyst involved in human drug oxidation, displays substrate- and reaction-dependent ... Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Court ... Nuclear receptor CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene. Inoue, K., Negishi, M. J ...
G. Gervasini, C. Martinez, J. Benitez, and J. A. Agúndez, "Effect of neurotransmitters on NADPH-cytochrome P450 reductase in ... "Role of the smoking-induced cytochrome P450 (CYP)1A2 and polymorphic CYP2D6 in steady-state concentration of olanzapine," ... Comparative Cytochrome P450 In Vitro Inhibition by Atypical Antipsychotic Drugs. Guillermo Gervasini, Maria J. Caballero, Juan ... J. G. Shin, N. Soukhova, and D. A. Flockhart, "Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in ...
Measurement of liver microsomal cytochrome p450 (CYP2D6) activity using [O-methyl-14C]dextromethorphan. Anal Biochem 219: 309- ... The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: Effect on human cytochrome P-450 and implications ... Integrated cytochrome P450 reaction phenotyping: Attempting to bridge the gap between cDNA-expressed cytochromes P450 and ... Crespi CL, Miller VP and Penman BW (1998) High throughput screening for inhibition of cytochrome P450 metabolism. Med Chem Res ...
Cytochrome P-450 CYP2D6. *Vitamin K Epoxide Reductases. Grant support. *16GRNT29300003/American Heart Association-American ... Commonly encountered gene-drug pairs for these interventions included: CYP2C19 for clopidogrel and antidepressants, CYP2D6 for ... Vitamin K Epoxide Reductases/genetics. *Warfarin/therapeutic use. Substances. *Liver-Specific Organic Anion Transporter 1 ...
4. Cytochrome P450 3A4. General function:. Involved in monooxygenase activity. Specific function:. Cytochromes P450 are a group ... CYP2D6. Uniprot ID:. P10635 Molecular weight:. 55768.94. References. *Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, ... 5. Cytochrome P450 2C9. General function:. Involved in monooxygenase activity. Specific function:. Cytochromes P450 are a group ... 9. Cytochrome P450 2B6. General function:. Involved in monooxygenase activity. Specific function:. Cytochromes P450 are a group ...
Vermes A, Vermes I. Genetic polymorphisms in cytochrome P450 enzymes: effect on efficacy and tolerability of HMG-CoA reductase ... Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6. Drug Metab ... Appetite suppressant drugs as inhibitors of human cytochromes P450: in vitro inhibition of P450-2D6 by D- and L-fenfluramine, ... by microsomal cytochrome P450 in humans, rats, and other species: probable involvement of CYP2D6 and CYP3A. Drug Metab Dispos ...
Whats the Cytochrome P-450 System?. The cytochrome P-450 system is located in the liver and it is in charge of metabolizing ... CBD inhibits CYP3A4 and CYP2D6, enhancing the quantities of drugs metabolized by these isoenzymes. (R) ... HMG CoA Reductase Inhibitors. *PDE-5 Inhibitors. Liquor, Cannabis, & CBD Oil. Given that rise in popularity of cannabidiol ... For folks who binge beverage or have chronic drinking habits, the cytochrome P-450 system gets included, especially the CYP2E1 ...
Effects of Fenofibrate on the Expression of Small Heterodimer Partner (SHP) and Cytochrome P450 (CYP) 2D6 ... Inhibitory Effect of Fruit Juices on the Doxorubicin Metabolizing Activity of Carbonyl Reductase 1 ... Cytochrome P450 1A2 Messenger RNA is a More Reliable Marker than Cytochrome P450 1A2 Activity, Phenacetin O-Deethylation, for ... Strong Induction of Cytochrome P450 1A/3A, But not P450 2B, in Cultured Hepatocytes from Common Marmosets and Cynomolgus ...
CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996; 50: 209-215. ... Human cytochrome P450 enzymes.In: Ortiz de Montellano PR, ed. Cytochrome P450: Structure, Mechanism, and Biochemistry.. New ... the tightness of enzyme coupling to the cytochrome P450 reductase or cytochrome b5.80,87 At the moment, nothing specific is ... oxidases in a multienzyme system that also includes a FAD/FMN-containing NADPH-cytochrome P450 reductase and cytochrome b5. CYP ...
Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354-62.PubMedCrossRefGoogle Scholar ... Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on ... Identification of the gene for vitamin K epoxide reductase. Nature. 2004;427(6974):541-4.PubMedCrossRefGoogle Scholar ... Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin ...
... substrates of CYP2D6 (e.g. including but not limited to thioridazine); inhibitors of CYP3A4 (e.g. including but not limited to ... 5-alpha-reductase inhibitors (e.g. finasteride [Proscar(R)], dutasteride [Avodart(R)]); steroidal anti-androgen therapy; any ...
  • J. Wójcikowski, J. Boksa, and W. A. Daniel, "Main contribution of the cytochrome P450 isoenzyme 1A2 (CYP1A2) to N -demethylation and 5-sulfoxidation of the phenothiazine neuroleptic chlorpromazine in human liver-a comparison with other phenothiazines," Biochemical Pharmacology , vol. 80, no. 8, pp. 1252-1259, 2010. (hindawi.com)
  • PB-BNF increased cytochrome P450 (CYP) activity and CYP1A1, CYP1A2, CYP2B1/2, CYP2C6, CYP3A1, and CYP3A2 expression in rat S9, whereas it decreased CYP2C11 and CYP2E1 expression. (go.jp)
  • Androstenone (5α-androst-16-en-3-one) is a 16-androstene steroid metabolised from cholesterol through the C 21 steroids pregnenolone and progesterone in boar testis [ 5 ]. (biomedcentral.com)
  • Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients. (ge-bu.nl)
  • In Caucasian populations, the prevalence of PMs is 5-10% ( 9 ), the majority of whom (90-95%) are homozygous for any of the known defective CYP2D6 alleles or combinations thereof ( 10 ). (aspetjournals.org)
  • NO inhibits the respiratory chain enzyme, cytochrome c oxidase, with an IC 50 of 60-120 nM at physiological oxygen concentrations [ 4 , 8 ], and micromolar NO levels can produce cell damage via reaction with superoxide and production of the highly oxidising species peroxynitrite [ 9 ]. (biochemj.org)