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.Cunninghamella: A genus of zygomycetous fungi of the family Cunninghamellaceae, order MUCORALES. Some species cause systemic infections in humans.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 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.Dealkylation: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)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.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.Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Biodegradation, Environmental: Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Trichloroethanes: Chlorinated ethanes which are used extensively as industrial solvents. They have been utilized in numerous home-use products including spot remover preparations and inhalant decongestant sprays. These compounds cause central nervous system and cardiovascular depression and are hepatotoxic. Include 1,1,1- and 1,1,2-isomers.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.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.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 Detoxication, Phase II: The conjugation of exogenous substances with various hydrophilic substituents to form water soluble products that are excretable in URINE. Phase II modifications include GLUTATHIONE conjugation; ACYLATION; and AMINATION. Phase II enzymes include GLUTATHIONE TRANSFERASE and GLUCURONOSYLTRANSFERASE. In a sense these reactions detoxify phase I reaction products.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.Trinitrotoluene: A 2,4,6-trinitrotoluene, which is an explosive chemical that can cause skin irritation and other toxic consequences.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Glucuronides: Glycosides of GLUCURONIC ACID formed by the reaction of URIDINE DIPHOSPHATE GLUCURONIC ACID with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and BILIRUBIN metabolism to a more water-soluble compound that can be eliminated in the URINE and BILE.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)Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of 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.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).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.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.Gordonia Bacterium: A genus of gram-positive BACTERIA in the family Gordoniaceae, isolated from soil and from sputa of patients with chest disorders. It is also used for biotransformation of natural products.Oxygenases: Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).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.Oxidoreductases, N-DemethylatingTroleandomycin: A macrolide antibiotic that is similar to ERYTHROMYCIN.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.Oncorhynchus kisutch: An anadromous species of SALMON ranging from the Arctic and Pacific Oceans to Monterey Bay, California and inhabiting ocean and coastal streams. It is familiarly known as the coho or silver salmon. It is relatively small but its light-colored flesh is of good flavor.Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Environmental Pollutants: Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS.Hydrocarbons, HalogenatedSpecies 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.Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid.Equol: A non-steroidal ESTROGEN generated when soybean products are metabolized by certain bacteria in the intestines.Glucuronates: Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.Methoxyflurane: An inhalation anesthetic. Currently, methoxyflurane is rarely used for surgical, obstetric, or dental anesthesia. If so employed, it should be administered with NITROUS OXIDE to achieve a relatively light level of anesthesia, and a neuromuscular blocking agent given concurrently to obtain the desired degree of muscular relaxation. (From AMA Drug Evaluations Annual, 1994, p180)Toluene: A widely used industrial solvent.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Nitroglycerin: A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.Berberidaceae: The Barberry plant family of the order Ranunculales, subclass Magnoliidae, class Magnoliopsida. The shrubs have spiny leaves.Arylamine N-Acetyltransferase: An enzyme that catalyzes the transfer of acetyl groups from ACETYL-COA to arylamines. It can also catalyze acetyl transfer between arylamines without COENZYME A and has a wide specificity for aromatic amines, including SEROTONIN. However, arylamine N-acetyltransferase should not be confused with the enzyme ARYLALKYLAMINE N-ACETYLTRANSFERASE which is also referred to as SEROTONIN ACETYLTRANSFERASE.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.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.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)Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Fenthion: Potent cholinesterase inhibitor used as an insecticide and acaricide.Monoterpenes: Compounds with a core of 10 carbons generally formed via the mevalonate pathway from the combination of 3,3-dimethylallyl pyrophosphate and isopentenyl pyrophosphate. They are cyclized and oxidized in a variety of ways. Due to the low molecular weight many of them exist in the form of essential oils (OILS, VOLATILE).Kinetics: The rate dynamics in chemical or physical systems.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.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Hepatophyta: A plant division. They are simple plants that lack vascular tissue and possess rudimentary rootlike organs (rhizoids). Like MOSSES, liverworts have alternation of generations between haploid gamete-bearing forms (gametophytes) and diploid spore-bearing forms (sporophytes).Norisoprenoids: Thirteen-carbon butene cyclohexene degradation products formed by the cleavage of CAROTENOIDS. They contribute to the flavor of some FRUIT. Ionone should not be confused with the similarly named ionol.Water Pollutants, Chemical: Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water.Ethylmorphine: A narcotic analgesic and antitussive. It is metabolized in the liver by ETHYLMORPHINE-N-DEMETHYLASE and used as an indicator of liver function.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.BenzaldehydesTandem Mass Spectrometry: A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.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.Mucorales: An order of zygomycetous fungi, usually saprophytic, causing damage to food in storage, but which may cause respiratory infection or MUCORMYCOSIS in persons suffering from other debilitating diseases.Ictaluridae: A family of North American freshwater CATFISHES. It consists of four genera (Ameiurus, Ictalurus, Noturus, Pylodictis,) comprising several species, two of which are eyeless.Hydrocarbons, Aromatic: Organic compounds containing carbon and hydrogen in the form of an unsaturated, usually hexagonal ring structure. The compounds can be single ring, or double, triple, or multiple fused rings.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.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.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.Ethylmercuric Chloride: A highly toxic compound used as a fungicide for treating seeds.Eugenol: A cinnamate derivative of the shikamate pathway found in CLOVE OIL and other PLANTS.Rhodococcus: A bacterial genus of the order ACTINOMYCETALES.Pseudomonas putida: A species of gram-negative, aerobic bacteria isolated from soil and water as well as clinical specimens. Occasionally it is an opportunistic pathogen.Isoflavones: 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Ethyl EthersSoil Pollutants: Substances which pollute the soil. Use for soil pollutants in general or for which there is no specific heading.Alprazolam: A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of PANIC DISORDERS, with or without AGORAPHOBIA, and in generalized ANXIETY DISORDERS. (From AMA Drug Evaluations Annual, 1994, p238)Ethoxyquin: Antioxidant; also a post-harvest dip to prevent scald on apples and pears.Hydrocarbons, Chlorinated: Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Spectrometry, Mass, Electrospray Ionization: A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry.Atrazine: A selective triazine herbicide. Inhalation hazard is low and there are no apparent skin manifestations or other toxicity in humans. Acutely poisoned sheep and cattle may show muscular spasms, fasciculations, stiff gait, increased respiratory rates, adrenal degeneration, and congestion of the lungs, liver, and kidneys. (From The Merck Index, 11th ed)Triazines: Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.Metabolic Engineering: Methods and techniques used to genetically modify cells' biosynthetic product output and develop conditions for growing the cells as BIOREACTORS.Aspergillus ochraceus: An imperfect fungus that produces ochratoxins and contaminates EDIBLE GRAIN and coffee beans.Ethylmercury Compounds: Organic mercury compounds in which the mercury is attached to an ethyl group.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.Parathion: A highly toxic cholinesterase inhibitor that is used as an acaricide and as an insecticide.Nuphar: A plant genus of the family NYMPHAEACEAE. Members contain sesquiterpene thioalkaloids.Batch Cell Culture Techniques: Methods for cultivation of cells, usually on a large-scale, in a closed system for the purpose of producing cells or cellular products to harvest.Flame Retardants: Materials applied to fabrics, bedding, furniture, plastics, etc. to retard their burning; many may leach out and cause allergies or other harm.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.tert-Butyl AlcoholCatechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.Lactobacillus brevis: A species of gram-positive, rod-shaped LACTIC ACID bacteria that is frequently used as starter culture in SILAGE fermentation, sourdough, and lactic-acid-fermented types of beer and wine.Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.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)Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber.Rats, Inbred F344Coumaric Acids: Hydroxycinnamic acid and its derivatives. Act as activators of the indoleacetic acid oxidizing system, thereby producing a decrease in the endogenous level of bound indoleacetic acid in plants.Pyrazolones: Compounds with a five-membered heterocyclic ring with two nitrogens and a keto OXYGEN. Some are inhibitors of TNF-ALPHA production.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.Photinia: A plant genus of the family ROSACEAE. The common names of chokeberry or chokecherry are also used for some species of PRUNUS.Skin Lightening Preparations: Substances used to obtain a lighter skin complexion or to treat HYPERPIGMENTATION disorders.Phenols: Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.Umbelliferones: 7-Hydroxycoumarins. Substances present in many plants, especially umbelliferae. Umbelliferones are used in sunscreen preparations and may be mutagenic. Their derivatives are used in liver therapy, as reagents, plant growth factors, sunscreens, insecticides, parasiticides, choleretics, spasmolytics, etc.L-Lysine 6-Transaminase: A PYRIDOXAL PHOSPHATE containing enzyme that catalyzes the transfer of amino group of L-LYSINE onto 2-oxoglutarate to generate 2-aminoadipate 6-semialdehyde and L-GLUTAMATE.Arsenic: A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed)Micromonospora: A genus of gram-positive bacteria that forms a branched mycelium. It commonly occurs as a saprophytic form in soil and aquatic environments.Dichloroethylenes: Toxic chlorinated unsaturated hydrocarbons. Include both the 1,1- and 1,2-dichloro isomers. Both isomers are toxic, but 1,1-dichloroethylene is the more potent CNS depressant and hepatotoxin. It is used in the manufacture of thermoplastic polymers.Octanes: Eight-carbon saturated hydrocarbon group of the methane series. Include isomers and derivatives.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.Carboxylesterase: Carboxylesterase is a serine-dependent esterase with wide substrate specificity. The enzyme is involved in the detoxification of XENOBIOTICS and the activation of ester and of amide PRODRUGS.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.NADPH-Ferrihemoprotein Reductase: A flavoprotein that catalyzes the reduction of heme-thiolate-dependent monooxygenases and is part of the microsomal hydroxylating system. EC Inorganic salts of hydrofluoric acid, HF, in which the fluorine atom is in the -1 oxidation state. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Sodium and stannous salts are commonly used in dentifrices.Butylene Glycols: 4-carbon straight chain aliphatic hydrocarbons substituted with two hydroxyl groups. The hydroxyl groups cannot be on the same carbon atom.Zearalenone: (S-(E))-3,4,5,6,8,10-Hexahydro-14,16-dihydroxy-3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione. One of a group of compounds known under the general designation of resorcylic acid lactones. Cis, trans, dextro and levo forms have been isolated from the fungus Gibberella zeae (formerly Fusarium graminearum). They have estrogenic activity, cause toxicity in livestock as feed contaminant, and have been used as anabolic or estrogen substitutes.Biocatalysis: The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.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.Polycyclic Hydrocarbons, Aromatic: A major group of unsaturated cyclic hydrocarbons containing two or more rings. The vast number of compounds of this important group, derived chiefly from petroleum and coal tar, are rather highly reactive and chemically versatile. The name is due to the strong and not unpleasant odor characteristic of most substances of this nature. (From Hawley's Condensed Chemical Dictionary, 12th ed, p96)Mercury Compounds: Inorganic compounds that contain mercury as an integral part of the molecule.Aminophenols: Phenols substituted in any position by an amino group.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.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.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.Dichloroacetic Acid: A derivative of ACETIC ACID that contains two CHLORINE atoms attached to its methyl group.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including MUSHROOMS; YEASTS; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies.Fluorenes: A family of diphenylenemethane derivatives.Guaiacol: An agent thought to have disinfectant properties and used as an expectorant. (From Martindale, The Extra Pharmacopoeia, 30th ed, p747)Metabolic Networks and Pathways: Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.Chlorella: Nonmotile unicellular green algae potentially valuable as a source of high-grade protein and B-complex vitamins.NorbornanesPyrrolizidine Alkaloids: A group of ALKALOIDS, characterized by a nitrogen-containing necine, occurring mainly in plants of the BORAGINACEAE; COMPOSITAE; and LEGUMINOSAE plant families. They can be activated in the liver by hydrolysis of the ester and desaturation of the necine base to reactive electrophilic pyrrolic CYTOTOXINS.Epoxide Hydrolases: Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.Anesthesia, Inhalation: Anesthesia caused by the breathing of anesthetic gases or vapors or by insufflating anesthetic gases or vapors into the respiratory tract.Mucor: A genus of zygomycetous fungi of the family Mucoraceae, order Mucorales. It is primarily saprophytic, but may cause MUCORMYCOSIS in man from spores germinating in the lungs.Pseudomonas mendocina: A species of gram-negative bacteria in the genus PSEUDOMONAS, which is found in SOIL and WATER.Trifluoroacetic Acid: A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis.Estrogens, Non-Steroidal: Non-steroidal compounds with estrogenic activity.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Halogenation: Covalent attachment of HALOGENS to other compounds.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Chromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Antimitotic Agents: Agents that arrest cells in MITOSIS, most notably TUBULIN MODULATORS.Aflatoxin B1: A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Transaldolase: An enzyme of the transferase class that catalyzes the reaction sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to yield D-erythrose 4-phosphate and D-fructose phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Xylenes: A family of isomeric, colorless aromatic hydrocarbon liquids, that contain the general formula C6H4(CH3)2. They are produced by the destructive distillation of coal or by the catalytic reforming of petroleum naphthenic fractions. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Mutagenicity Tests: Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.Safety-Based Drug Withdrawals: Removal of a drug from the market due to the identification of an intrinsic property of the drug that results in a serious risk to public health.Anemarrhena: A plant genus of the family LILIACEAE. Members contain anemarans (POLYSACCHARIDES), hinokiresinol, mangiferin (a xanthone), and timosaponin (a steroidal saponin).Safrole: A member of the BENZODIOXOLES that is a constituent of several VOLATILE OILS, notably SASSAFRAS oil. It is a precursor in the synthesis of the insecticide PIPERONYL BUTOXIDE and the drug N-methyl-3,4-methylenedioxyamphetamine (MDMA).Halothane: A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178)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.Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2.Alkanes: The generic name for the group of aliphatic hydrocarbons Cn-H2n+2. They are denoted by the suffix -ane. (Grant & Hackh's Chemical Dictionary, 5th ed)Nitro Compounds: Compounds having the nitro group, -NO2, attached to carbon. When attached to nitrogen they are nitramines and attached to oxygen they are NITRATES.Styrenes: Derivatives and polymers of styrene. They are used in the manufacturing of synthetic rubber, plastics, and resins. Some of the polymers form the skeletal structures for ion exchange resin beads.Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc.Biological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Toxicity Tests: An array of tests used to determine the toxicity of a substance to living systems. These include tests on clinical drugs, foods, and environmental pollutants.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.-.Trichloroethylene: A highly volatile inhalation anesthetic used mainly in short surgical procedures where light anesthesia with good analgesia is required. It is also used as an industrial solvent. Prolonged exposure to high concentrations of the vapor can lead to cardiotoxicity and neurological impairment.Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen.Hydrocarbons, FluorinatedPolychlorinated 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.Polycyclic Compounds: Compounds consisting of two or more fused ring structures.Methyl Ethers: A group of compounds that contain the general formula R-OCH3.

Carcinogenicity of triethanolamine in mice and its mutagenicity after reaction with sodium nitrite in bacteria. (1/3890)

Mice fed a diet containing 0.3 or 0.03% triethanolamine developed malignant tumors. Females showed a high incidence of tumors in lymphoid tissues, while this type was absent in males. Tumors in other tissues were produced at a considerable rate in both sexes, but no hepatoma was found. Triethanolamine was not mutagenic to Bacillus subtilis by itself, but it became mutagenic after reacting with sodium nitrite under acidic conditions or when the mixture was heated. Although N-nitrosodiethanolamine, a known carcinogen and mutagen, was detected in the reaction mixture by thin-layer chromatography, it may not be the main mutagenic product, because the product was a stable and direct mutagen and its mutagenic activity was destroyed by liver enzymes, unlike N-nitrosodiethanolamine. The lethal and mutagenic DNA damages produced by this unidentified product were susceptible to some extent to the repair functions of the bacteria.  (+info)

Enantioselective inhibition of the biotransformation and pharmacological actions of isoidide dinitrate by diphenyleneiodonium sulphate. (2/3890)

1. We have shown previously that the D- and L- enantiomers of isoidide dinitrate (D-IIDN and L-IIDN) exhibit a potency difference for relaxation and cyclic GMP accumulation in isolated rat aorta and that this is related to preferential biotransformation of the more potent enantiomer (D-IIDN). The objective of the current study was to examine the effect of the flavoprotein inhibitor, diphenyleneiodonium sulphate (DPI), on the enantioselectivity of IIDN action. 2. In isolated rat aortic strip preparations, exposure to 0.3 microM DPI resulted in a 3.6 fold increase in the EC50 value for D-IIDN-induced relaxation, but had no effect on L-IIDN-induced relaxation. 3. Incubation of aortic strips with 2 microM D- or L-IIDN for 5 min resulted in significantly more D-isoidide mononitrate formed (5.0 +/- 1.5 pmol mg protein(-1)) than L-isoidide mononitrate (2.1 +/- 0.7 pmol mg protein(-1)) and this difference was abolished by pretreatment of tissues with 0.3 microM DPI. DPI had no effect on glutathione S-transferase (GST) activity or GSH-dependent biotransformation of D- or L-IIDN in the 105,000 x g supernatant fraction of rat aorta. 4. Consistent with both the relaxation and biotransformation data, treatment of tissues with 0.3 microM DPI significantly inhibited D-IIDN-induced cyclic GMP accumulation, but had no effect on L-IIDN-induced cyclic GMP accumulation. 5. In the intact animal, 2 mg kg(-1) DPI significantly inhibited the pharmacokinetic and haemodynamic properties of D-IIDN, but had no effect L-IIDN. 6. These data suggest that the basis for the potency difference for relaxation by the two enantiomers is preferential biotransformation of D-IIDN to NO, by an enzyme that is inhibited by DPI. Given that DPI binds to and inhibits NADPH-cytochrome P450 reductase, the data are consistent with a role for the cytochromes P450-NADPH-cytochrome P450 reductase system in this enantioselective biotransformation process.  (+info)

Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas. (3/3890)

CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different tissues, such as lung, of the CYP1B1-null mouse treated with the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin whereas the equivalent wild-type EF cells express basal and substantial inducible CYP1B1 and lung expresses inducible CYP1B1. CYP1A1 is induced to far higher levels than CYP1B1 in liver, kidney, and lung in wild-type mice and is induced to a similar extent in CYP1B1-null mice. 7,12-dimethylbenz[a]anthracene (DMBA) was toxic in wild-type EFs that express CYP1B1 but not CYP1A1. These cells effectively metabolized DMBA, consistent with CYP1B1 involvement in producing the procarcinogenic 3,4-dihydrodiol as a major metabolite, whereas CYP1B1-null EF showed no significant metabolism and were resistant to DMBA-mediated toxicity. When wild-type mice were administered high levels of DMBA intragastrically, 70% developed highly malignant lymphomas whereas only 7.5% of CYP1B1-null mice had lymphomas. Skin hyperplasia and tumors were also more frequent in wild-type mice. These results establish that CYP1B1, located exclusively at extrahepatic sites, mediates the carcinogenicity of DMBA. Surprisingly, CYP1A1, which has a high rate of DMBA metabolism in vitro, is not sufficient for this carcinogenesis, which demonstrates the importance of extrahepatic P450s in determining susceptibility to chemical carcinogens and validates the search for associations between P450 expression and cancer risk in humans.  (+info)

Microbial desulfurization of organic sulfur compounds in petroleum. (4/3890)

Sulfur removal from petroleum is important from the standpoint of the global environment because the combustion of sulfur compounds leads to the production of sulfur oxides, which are the source of acid rain. As the regulations for sulfur in fuels become more stringent, the existing chemical desulfurizations are coming inadequate for the "deeper desulfurization" to produce lower-sulfur fuels without new and innovative processes. Biodesulfurization is rising as one of the candidates. Several microorganisms were found to desulfurize dibenzothiophene (DBT), a representative of the organic sulfur compounds in petroleum, forming a sulfur-free compound, 2-hydroxybiphenyl. They are promising as biocatalysts in the microbial desulfurization of petroleum because without assimilation of the carbon content, they remove only sulfur from the heterocyclic compounds which is refractory to conventional chemical desulfurization. Both enzymological and molecular genetic studies are now in progress for the purpose of obtaining improved desulfurization activity of organisms. The genes involved in the sulfur-specific DBT desulfurization were identified and the corresponding enzymes have been investigated. From the practical point of view, it has been proved that the microbial desulfurization proceeds in the presence of high concentrations of hydrocarbons, and more complicated DBT analogs are also desulfurized by the microorganisms. This review outlines the progress in the studies of the microbial desulfurization from the basic and practical point of view.  (+info)

Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and in human hepatocytes: identification of glutathione conjugated metabolites. (5/3890)

The nonsteroidal anti-inflammatory drug diclofenac causes a rare but potentially fatal hepatotoxicity that may be associated with the formation of reactive metabolites. In this study, three glutathione (GSH) adducts, namely 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified by liquid chromatography-tandem mass spectrometry analysis of bile from Sprague-Dawley rats injected i.p. with a single dose of diclofenac (200 mg/kg). These adducts presumably were formed via hepatic cytochrome P-450 (CYP)-catalyzed oxidation of diclofenac to reactive benzoquinone imines that were trapped by GSH conjugation. In support of this hypothesis, M1, M2, and M3 were generated from diclofenac in incubations with rat liver microsomes in the presence of NADPH and GSH. Increases in adduct formation were observed when incubations were performed with liver microsomes from phenobarbital- or dexamethasone-treated rats. Adduct formation was inhibited by polyclonal antibodies against CYP2B, CYP2C, and CYP3A (40-50% inhibition at 5 mg of IgG/nmol of CYP) but not by an antibody against CYP1A. Maximal inhibition was obtained when the three inhibitory antibodies were used in a cocktail fashion (70-80% inhibition at 2.5 mg of each IgG/nmol of CYP). These data suggest that diclofenac undergoes biotransformation to reactive metabolites in rats and that CYP isoforms of the 2B, 2C, and 3A subfamilies are involved in this bioactivation process. With respect to CYP2C isoforms, rat hepatic CYP2C7 and CYP2C11 were implicated as mediators of the bioactivation based on immunoinhibition studies using antibodies specific to CYP2C7 and CYP2C11. Screening for GSH adducts also was carried out in human hepatocyte cultures containing diclofenac, and M1, M2, and M3 again were detected. It is possible, therefore, that reactive benzoquinone imines may be formed in vivo in humans and contribute to diclofenac-mediated hepatic injury.  (+info)

Oxidative bioactivation of the lactol prodrug of a lactone cyclooxygenase-2 inhibitor. (6/3890)

The lactol derivative of a lactone cyclooxygenase-2 inhibitor (DFU) was evaluated in vivo and in vitro for its potential suitability as a prodrug. DFU-lactol was found to be 10 to 20 times more soluble than DFU in a variety of aqueous vehicles. After administration of DFU-lactol at 20 mg kg-1 p.o. in rats, a Cmax of 7.5 microM DFU was reached in the plasma. After oral administration, the ED50s of DFU-lactol in the carrageenan-induced paw edema and lipopolysaccharide-induced pyresis assays in rats are comparable with the ED50s observed when dosing with DFU. Incubations of DFU-lactol with rat and human hepatocytes demonstrated that the oxidation of DFU-lactol can be mediated by liver enzymes and that a competing pathway is direct glucuronidation of the DFU-lactol hydroxyl group. Assays with subcellular fractions from rat liver indicated that most of the oxidation of DFU-lactol occurs in the cytosolic fraction and requires NAD(P)+. Human liver cytosol can also support the oxidation of DFU-lactol to DFU when NAD(P)+ is added to the incubations. Fractionation of human liver cytosolic proteins showed that at least three enzymes are capable of efficiently effecting the oxidation of DFU-lactol to DFU. Incubations with commercially available dehydrogenases suggest that alcohol and hydroxysteroid dehydrogenases are involved in this oxidative process. These data together suggest that lactols may represent useful prodrugs for lactone-containing drugs.  (+info)

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. (7/3890)

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was metabolized by human liver microsomes to 5-hydroxy-, 6-hydroxy-, and N-deisopropyl-fluvastatin. Total metabolite formation was biphasic with apparent Km values of 0.2 to 0.7 and 7.9 to 50 microM and intrinsic metabolic clearance rates of 1.4 to 4 and 0.3 to 1.5 ml/h/mg microsomal protein for the high and low Km components, respectively. Several enzymes, but mainly CYP2C9, catalyzed fluvastatin metabolism. Only CYP2C9 inhibitors such as sulfaphenazole inhibited the formation of both 6-hydroxy- and N-deisopropyl-fluvastatin. 5-Hydroxy-fluvastatin formation was reduced by compounds that are inhibitors of CYP2C9, CYP3A, or CYP2C8. Fluvastatin in turn inhibited CYP2C9-catalyzed tolbutamide and diclofenac hydroxylation with Ki values of 0.3 and 0.5 microM, respectively. For CYP2C8-catalyzed 6alpha-hydroxy-paclitaxel formation the IC50 was 20 microM and for CYP1A2, CYP2C19, and CYP3A catalyzed reactions, no IC50 could be determined up to 100 microM fluvastatin. All three fluvastatin metabolites were also formed by recombinant CYP2C9, whereas CYP1A1, CYP2C8, CYP2D6, and CYP3A4 produced only 5-hydroxy-fluvastatin. Km values were approximately 1, 2.8, and 7.1 microM for CYP2C9, CYP2C8, and CYP3A, respectively. No difference in fluvastatin metabolism was found between the CYP2C9R144 and CYP2C9C144 alleles, suggesting the absence of polymorphic fluvastatin metabolism by these alleles. CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2E1, and CYP3A5 did not produce detectable amounts of any metabolite. This data indicates that several human cytochrome P-450 enzymes metabolize fluvastatin with CYP2C9 contributing 50-80%. Any coadministered drug would therefore only partially reduce the metabolic clearance of fluvastatin; therefore, the likelihood for serious metabolic drug interactions is expected to be minimal.  (+info)

Rapid liquid chromatography with tandem mass spectrometry-based screening procedures for studies on the biotransformation of drug candidates. (8/3890)

The accelerated pace of contemporary drug discovery and development in the pharmaceutical industry has generated increasing demands for early information on the metabolic fate of candidate drugs to guide the selection of new compounds for clinical evaluation. In response to these demands, we have developed a procedure for the rapid analysis of complex biological mixtures for the presence of drug-related materials and have embarked on the development of novel computer-based approaches whereby such procedures can be automated. The goal of this work was to rapidly identify drug metabolites (derived either from a single substrate or from a mixture of substrates) formed in vivo or in vitro. The approach that we have developed relies on the use of generic chromatographic and mass spectrometric methods for analysis of mixtures of drugs and metabolites and on correlation analysis of tandem mass spectrometry spectra to distinguish drug-related components from endogenous materials. Cross-correlation of the spectra also is used to identify the relationship between each metabolite and its respective parent drug in the mixture. In this manner, metabolites of a mixture of several drugs may be analyzed in the time it normally would take to analyze the products from a single substrate. We show that this rapid analytical approach can, with only minor sacrifices in the completeness of the data, significantly increase the number of compounds whose metabolic fate can be elucidated in a given time.  (+info)

  • Biotransformations can also be used to synthesize compounds or materials, if synthetic approaches are challenging. (
  • Biotransformation approaches and synthetic methods in tandem provide a source for generating compounds around core structures, which can be screened for various biological activity studies. (
  • Hence, biotransformation experiments can be effectively utilized to synthesize more compounds. (
  • Biotransformation is one of the important experimental methods to identify compounds, whose structure and properties resembles the parent compound. (
  • The study reviews the current state of knowledge regarding the biotransformation of fluorotelomer-based compounds, with a focus on compounds that ultimately degrade to form perfluoroalkyl carboxylates (PFCAs). (
  • Luckily, we can use nutrition through food and supplements, herbs, lifestyle changes and other healing modalities to support this biotransformation system and help increase the proper removal of mycotoxins and other toxins from the body. (
  • Fragmentation pattern obtained from the mass spectrum is utilized to identify the biotransformation site in the molecule, which is the metabolic soft spot. (
  • These often include the use of mass defect filtering, isotope matching, inclusion/exclusion lists and may involve a database of known established Phase 1 and Phase 2 biotransformations rules to determine the presence of these components. (
  • the pathways of drug metabolism can be divided into: phase І phase II Drugs can undergo one of four potential biotransformations: Active Drug to Inactive Metabolite, Active Drug to Active Metabolite, Inactive Drug to Active Metabolite, Active Drug to Toxic Metabolite (biotoxification). (
  • Major methodological breakthroughs in recent years have enabled detailed genomic, metagenomic, proteomic, bioinformatic and other high-throughput analyses of environmentally relevant microorganisms providing unprecedented insights into biotransformation and biodegradative pathways and the ability of organisms to adapt to changing environmental conditions. (
  • In the field of Environmental Microbiology, genome-based global studies open a new era providing unprecedented in silico views of metabolic and regulatory networks, as well as clues to the evolution of biochemical pathways relevant to biotransformation and to the molecular adaptation strategies to changing environmental conditions. (
  • Functional genomic and metagenomic approaches are increasing our understanding of the relative importance of different pathways and regulatory networks to carbon flux in particular environments and for particular compounds and they are accelerating the development of bioremediation technologies and biotransformation processes. (
  • Hands-on LC/MS experience and proven abilities in determining the biotransformation pathways of drugs by drug metabolizing enzymes. (
  • An effective way to counteract them is through biodegradation by natural metabolic pathways, a process called biotransformation. (
  • The samples were also measured for As speciation using HPLC-ICP-MS to investigate potential As biotransformation pathways. (
  • This study proposes that fungal pathways must be considered for the biotransformation of potential PFAS precursors, such as 6:2 FTOH, and suggests the basis for selecting proper microorganisms for remediation of fluoroalkyl‐contaminated sites. (
  • However, very little is known regarding the interactions between PBDEs and the gut microbiome, and how such interactions modify the hepatic xenobiotic biotransformation and intermediary metabolism pathways. (
  • Taken together, the present study revealed for the first time that there is a novel interaction between the gut microbiome and PBDEs, and this markedly impacts both xenobiotic biotransformation and intermediary metabolism pathways in the host liver. (
  • The focus of his research group is elucidating novel biotransformation products and pathways of emerging contaminants to inform improved design of engineered natural treatment systems for non-point pollutants. (
  • Biotransformation pathways of ginsenosides Rb1, Rd, Rb2, Rb3, and Rc by recombinant BglPm and incorporated pathways for F2 production by two glycoside hydrolases. (
  • The metabolism of a drug or toxin in a body is an example of a biotransformation. (
  • The terms metabolism and biotransformation are used interchangeably in this book. (
  • The DMPK biotransformation group at Genentech is seeking a highly motivated individual to support development drug metabolism. (
  • To investigate the biotransformation of pantoprazole, a proton-pump inhibitor, by filamentous fungus and further to compare the similarities between microbial transformation and mammalian metabolism of pantoprazole, four strains of Cunninghamella (C. blakesleeana AS 3.153, C. echinulata AS 3.2004, C. elegans AS 3.156, and AS 3.2028) were screened for the ability to catalyze the biotransformation of pantoprazole. (
  • Our findings indicate that As(V) accumulation and its subsequent biotransformation were enhanced by organic P forms, which provides new insight into how DOP modulates As metabolism in algae. (
  • Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role of cytochrome P450s and alcohol dehydrogenase in biotransformation. (
  • However, very little evidences on fungal degradation or biotransformation of EHCO have been reported, which contain high amounts of asphaltenes and its biodegradation rate is very limited. (
  • We selected three cell lines from different tissues to more fully account for whole-body biotransformation in vivo: the RTL-W1 cell line, representing the liver as major site of biotransformation, and the RTgill-W1 (gill) and RTgutGC (intestine) cell lines, as important environment-organism interfaces, which likely influence chemical uptake. (
  • Consequently, the whole body biotransformation rate of a chemical is retarded by the extent of its distribution in different biological compartments. (
  • Using a randomly generated training set (n = 64), the biotransformation model is found to be: log(HLφfish) = 2.2(± 0.3)B − 2.1(± 0.2)V − 0.6(± 0.3) (RMSE = 0.71), where HL is the whole body biotransformation half‐life in days, φfish is the freely dissolved fraction in body fluid, and B and V are the chemical's H‐bond acceptance capacity and molecular volume. (
  • Fragmentation pattern obtained from the mass spectrum is utilized to identify the biotransformation site in the molecule, which is the metabolic soft spot. (
  • Minimum biotransformation rates, calculated from enantiomer mass balances between predators and prey, suggest metabolic half-lives on the order of 8 yr for CB 136 in lake trout and 2.6 yr for CB 95 in sculpins. (
  • We do this by measuring chemical uptake and biotransformation rates not only in cells of a rainbow trout liver cell line (RTL-W1), but also an intestinal (RTgutGC) as well as a gill (RTgill-W1) cell line to account for possible sites of biotransformation other than the liver. (
  • Together with previously analysed levels of these contaminants in plasma of the same mother-pup pairs, these results put together were used to examine in detail the maternal transfer (placental/lactational) and uptake and biotransformation in the pups. (
  • Widely nonracemic PCB residues in forage fish (lake herring, rainbow smelt, and slimy sculpin) and lake trout suggest a combination of both in vivo biotransformation and uptake of nonracemic residues from prey for these species. (
  • In contrast, aerobic biotransformation half-lives should be easier to extract from OECD 309 experiments with suspended sediments. (
  • Overall, k'bio has the potential to serve as a system-independent descriptor of aerobic biotransformation at the water-sediment interface that is equally and consistently applicable for both persistence and exposure assessment purposes. (
  • Biocatalysis & Biotransformation publishes 6 issues per year in simultaneous print and online editions. (
  • Subscribers to the electronic edition of Biocatalysis & Biotransformation receive access to the online archive, which dates back to 1987, as part of their subscription. (
  • It clarifies principles in reaction and biochemical engineering, synthetic and biotransformation chemistry, and biocell and enzyme kinetics for successful applications of biocatalysis and bioprocess technologies in the food, chiral drug, vitamin, pharmaceutical, and animal feed industries. (
  • Our aim was to find a way to extract biotransformation rate constants that are universally valid across variants of water-sediment systems and, hence, provide a more general description of the compound's behavior in the environment. (
  • TY - JOUR T1 - Biotransformation of pantoprazole by the fungus Cunninghamella blakesleeana. (
  • Biotransformation of alpha-cedrol and caryophyllene oxide by the fungus Neurospora crassa. (
  • Biotransformation of alpha- and 6beta-santonin by fungus and plant cell cultures. (
  • Prior to this study, one report demonstrated that the 6:2 FTOH biotransformation by the wood‐decaying fungus, Phanerochaete chrysosporium, generated more polyfluoroalkyl substances, such as 5:3 acid (F(CF2)5CH2CH2COOH), and diverted away from producing the highly stable perfluorocarboxylic acids (PFCAs). (
  • Only limited information is available on the effects of dissolved organic phosphorus (DOP) on arsenate (As(V)) bioaccumulation and biotransformation in organisms. (
  • PCB atropisomers were racemic in phytoplankton and zooplankton, suggesting no biotransformation potential toward PCBs for these low trophic level organisms. (
  • Biotransformation of various pollutants is a sustainable way to clean up contaminated environments. (
  • Absorption and biotransformation of polybrominated diphenyl ethers DE-" by Moira A. McKernan, Barnett A. Rattner et al. (
  • Our research focuses on the fundamental mechanisms related to the microbial and vegetative biotransformation of emerging contaminants in aquatic environments. (
  • 2018. "Sequential Biotransformation of Antcin K by Bacillus subtilis ATCC 6633. (
  • In this study, preliminary investigations on biotransformation of under utilized Moringa oleifera and Citrullus lanatus seed oils were carried out using baker s yeast ( Saccharomyces cerevisiae ). (
  • The enantiomeric composition of seven chiral PCB congeners was measured in the Lake Superior aquatic food web sampled in 1998, to determine the extent of enantioselective biotransformation in aquatic biota. (
  • Its susceptibility to microbiological breakdown was studied in a batch biotransformation system, in presence or absence of carbon source and at two activated sludge concentrations. (
  • A pilot scale biological nutrient removal (BNR) process, batch experiments and modeling exercises were employed to investigate the removal and biotransformation of trimethoprim (TMP) in a BNR activated sludge process. (
  • Batch tests with and without nitrification inhibition showed that AOB played a role in the biotransformation of TMP in BNR activated sludge. (
  • Dissolved organic phosphorus enhances arsenate bioaccumulation and biotransformation in Microcystis aeruginosa. (
  • Wang Z, Gui H, Luo Z, Zhen Z, Yan C, Xing B. Dissolved organic phosphorus enhances arsenate bioaccumulation and biotransformation in Microcystis aeruginosa. (
  • For the drug to get excreted into urine or bile it has to undergo a series of transformation which is called biotransformation. (
  • use in toxicology and xenobiotic biotransformations in REPE, which takes the administration of being air and body. (
  • use in toxicology and xenobiotic biotransformations solution mali come thick and persons are the formations semper, image-based opinion, relations, same map and see of viewing mistake in same hours, according individuals, enquiries, and presently1 remoteness. (
  • use in toxicology and xenobiotic biotransformations of same aliquid is to form and this three ad sub by Drs. Gupta, Mahendra Kumar and Vandana Gupta destroys a free grief to the twofold lakes on the idea. (
  • Biotransformation of Agricultural Waste and By-Products in the 4F Economy: The Food, Feed, Fiber, Fuel (4F) Economy presents an evaluation of plant species better exploitable for a particular transformation. (
  • These results suggest that the biotransformation of inorganic arsenic to organic species does not contribute to As resistance in the sampled earthworm populations. (
  • Biotransformation is the chemical modification (or modifications) made by an organism on a chemical compound. (
  • A new triterpenoid compound (1) and a known compound (2) were isolated from the product of biotransformation of glycyrrhizic acid by Aspergillus niger. (
  • Although dissipation half-lives of the parent compound are directly extractable from OECD 308 data, they are system-specific and mix up phase transfer with biotransformation. (
  • This result suggests that significant biotransformation may occur for metaboliz able PCB congeners over the lifespan of these biota. (
  • Overall, our results provided a solid scientific basis for understanding the chemopreventative mechanisms of RES from the perspective of biotransformation and gut microbiota and are of great value for future research on RES in prevention and treatment of colonic diseases in humans. (