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.
The process of cleaving a chemical compound by the addition of a molecule of water.
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.
A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17.
A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones.
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.
Mutant strain of Rattus norvegicus which is used as a disease model of kernicterus.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
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.
A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.
Analogs or derivatives of morphine.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
A group of hydroxycorticosteroids bearing a hydroxy group at the 17-position. Urinary excretion of these compounds is used as an index of adrenal function. They are used systemically in the free alcohol form, but with esterification of the hydroxy groups, topical effectiveness is increased.
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.
The rate dynamics in chemical or physical systems.
A bile pigment that is a degradation product of HEME.
A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin.
Linear TETRAPYRROLES that give a characteristic color to BILE including: BILIRUBIN; BILIVERDIN; and bilicyanin.
A plant genus of the family ASTERACEAE that is similar to CONYZA. Members contain SESQUITERPENES.
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)
Cholestanes substituted in any position with one or more hydroxy groups. They are found in feces and bile. In contrast to bile acids and salts, they are not reabsorbed.
A metabolite of TESTOSTERONE or ANDROSTENEDIONE with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.
A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.
A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties.
An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Chromatographic techniques in which the mobile phase is a liquid.
Inorganic salts of sulfuric acid.
A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.
A coumarin derivative possessing properties as a spasmolytic, choleretic and light-protective agent. It is also used in ANALYTICAL CHEMISTRY TECHNIQUES for the determination of NITRIC ACID.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
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)
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)
A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.
Very toxic industrial chemicals. They are absorbed through the skin, causing lethal blood, bladder, liver, and kidney damage and are potent, broad-spectrum carcinogens in most species.
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.
A group of 4-keto-FLAVONOIDS.
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)
A genus of chiefly Eurasian and African land snails including the principal edible snails as well as several pests of cultivated plants.
Rats bearing mutant genes which are phenotypically expressed in the animals.
A sugar acid formed by the oxidation of the C-6 carbon of GLUCOSE. In addition to being a key intermediate metabolite of the uronic acid pathway, glucuronic acid also plays a role in the detoxification of certain drugs and toxins by conjugating with them to form GLUCURONIDES.
A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.
A group of FLAVONOIDS characterized with a 4-ketone.
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.
Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)
An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.
The addition of an organic acid radical into a molecule.
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.
An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from ANDROSTENEDIONE directly, or from TESTOSTERONE via ESTRADIOL. In humans, it is produced primarily by the cyclic ovaries, PLACENTA, and the ADIPOSE TISSUE of men and postmenopausal women.
Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.
The chemical and physical integrity of a pharmaceutical product.
The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.
Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
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).
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
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.
Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Proteins prepared by recombinant DNA technology.
The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.
Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.
Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)
A group of phenyl benzopyrans named for having structures like FLAVONES.
An extraction method that separates analytes using a solid phase and a liquid phase. It is used for preparative sample cleanup before analysis by CHROMATOGRAPHY and other analytical methods.
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)
The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties.
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.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
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.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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.
Treatment process involving the injection of fluid into an organ or tissue.
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.
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.
The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.
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.
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.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
Uptake of substances through the lining of the INTESTINES.
Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.
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)
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.
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.
The giving of drugs, chemicals, or other substances by mouth.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
Multisubunit enzymes that reversibly synthesize ADENOSINE TRIPHOSPHATE. They are coupled to the transport of protons across a membrane.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
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.
Elements of limited time intervals, contributing to particular results or situations.
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).
An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.
Inorganic salts of phosphoric acid.
Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.
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).
Injections made into a vein for therapeutic or experimental purposes.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
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.
A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.
Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation.
Proteins found in any species of bacterium.
Kamata T, Nishikawa M, Katagi M, Tsuchihashi H (2003). "Optimized glucuronide hydrolysis for the detection of psilocin in human ... Some psilocin is not broken down by enzymes and instead forms a glucuronide; this is a biochemical mechanism animals use to ...
Deepoxidation and glucuronide conjugation do also occur. Ht-2 is the main metabolite. For the hydroxylation, the cytochrome ... In red blood cells T-2 mycotoxin is metabolized to neosolaniol, and, in white blood cells, to HT-2 via hydrolysis catalyzed by ... In vivo studies showed that the most occurring reactions are ester hydrolysis and hydroxylation of the isovaleryl group. ...
In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed. In March 2010, the U.S. Food and Drug ... Metabolism and elimination: In vitro and in vivo, clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative. ...
The scutellarin (Scutellarein-7-glucuronide) is transformed by hydrolysis into scutellarein. UmiKalsom, Yusuf; Harborne, ...
Metabolism and elimination: In vitro and in vivo, clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative. ... In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed. ... The two structures at the bottom are tautomers of each other; and the final step is a hydrolysis. The active metabolite (top ...
Major metabolic pathways were alkyl and indazole hydroxylation, terminal amide hydrolysis, subsequent glucuronide conjugations ...
... may undergo further metabolism via conjugation into tizoxanide glucuronide. Korba BE, Montero AB, Farrar K, et al. ( ... is a thiazolide and an antiparasitic agent that occurs as a metabolite of nitazoxanide in humans through hydrolysis. ...
It is one of the two conjugates of benzoic acid produced metabolically, the other being the glucuronide. Both are eliminated ... Benzoic acid is introduced into the body by ingestion (sodium benzoate is used as a preservative) and by hydrolysis of ...
The main metabolic pathway involves the hydrolysis of the hydroxyl groups followed by a series of reactions, such as taurine, ... sulfate and glucuronide conjugation. In humans, the majority of excretion of Geniposide is urinary. Hepatoxicity is the major ...
Some of the water-soluble conjugates are excreted via the bile duct, and partly reabsorbed after hydrolysis from the intestinal ... Estradiol is excreted in the form of glucuronide and sulfate estrogen conjugates in urine. Following an intravenous injection ... estradiol glucuronide and, as such, excreted via the kidneys. ...
Another study identifies 5,6,7-trihydroxy-2'- methoxyflavone and its 7-O-glucuronide. A number of the flavones found in S. ... Scutellarin is transformed by hydrolysis into scutellarein. Other plants with sedative GABAergic properties Piper methysticum ( ...
It is rapidly converted by hepatic enzymatic hydrolysis to the active form valdecoxib. The compound then undergoes another ... but a non CYP450 metabolism pathway to glucuronide metabolite is also at hand. A very small portion of etoricoxib (. ... is then further metabolized by non-cytochrome P450 pathway to a glucuronide metabolite. These metabolites are excreted in the ... to hydroxylated metabolite and glucuronide metabolite. The hydroxylated metabolite, that also has weak COX-2-specific ...
... or hydrolysis of the glucuronide can occur producing free bilirubin which is less reactive. Intestinal bacteria convert the ... The urine test strip reaction is based on the action of leukocyte esterase in catalysing the hydrolysis of an ester of ... In acid medium Bilirubin glucuronide + Diazonium salt→ Azo dye (violet) False positive reactions can be due to unusual pigments ...
Unlike other estradiol esters, polyestradiol phosphate is resistant to hydrolysis, which may be because it is a phosphatase ... as in estradiol glucuronide, and others (e.g., estramustine phosphate (estradiol 3-normustine 17β-phosphate)). These esters are ... for instance estrogen conjugates like estrone sulfate and estrone glucuronide and the very long-lived lipoidal estradiol, which ...
This process is analogous to hydrolysis of X-gal by Beta-galactosidase to produce blue cells as is commonly practiced in ... The insertion of the uidA gene will cause production of GUS, which can then be detected using various glucuronides as ... There are different possible glucuronides that can be used as substrates for the β-glucuronidase, depending on the type of ... For other types of detection, common substrates are p-nitrophenyl β-D-glucuronide for the spectrophotometric assay and 4- ...
Ertugliflocin is metabolised mainly to glucuronides by the enzymes UGT1A9 and UGT2B7. Cytochrome P450 enzymes play only a minor ... The high proportion of unchanged substance in the feces is probably due to hydrolysis of the metabolites back to the parent ...
D-glucuronate The enzyme also hydrolyses wogonin 7-O-beta-D-glucuronide and oroxylin 7-O-beta-D-glucuronide with lower ...
... as it is then less easily excreted from the body in its SN-38 glucuronide form. SN-38 and its glucuronide are lost into the ... SN38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1A1. The variant of ...
Only in dogs glucuronide could be found in the bile which is a sure sign of metabolism in that species. Also no differences in ... A Sandmeyer reaction by diazotization of 2-(4-aminophenyl)propanenitrile (1) followed by acid hydrolysis leads to phenol (2), ... In man and dog, the compound was excreted as the ester glucuronide, and in the other species as the unchanged compound. This ... enantiomer and glucuronide conjugation will metabolize benoxaprofen. However, benoxaprofen will not readily undergo oxidative ...
The second nucleotide binding domain, NBD2, is the domain responsible for the hydrolysis of ATP. This asymmetry is specific to ... This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternative splicing by ...
During phase I metabolism, mitragynine undergoes hydrolysis of the methylester group on C16 as well as o-demethylation of both ... During phase II metabolism, phase I metabolites undergo glucuronidation and sulfation to form multiple glucuronide and sulfate ...
J. W. Walker; V. K. Krieble (1909). "The hydrolysis of amygdalin by acids. Part I". Journal of the Chemical Society. 95 (11): ... transported intact to the liver and converted to a beta-glucuronide complex, which was then carried to the cancerous cells, ... Laetrile is synthesized from amygdalin by hydrolysis. The usual preferred commercial source is from apricot kernels (Prunus ... Liebig and Wöhler found three hydrolysis products of amygdalin: sugar, benzaldehyde, and prussic acid (hydrogen cyanide, HCN). ...
These can be activated by enzyme hydrolysis, which causes the sugar part to be broken off, making the chemical available for ... the resulting glucuronides are then excreted. Compounds can also be generally defined based on the class of glycone; for ... For example, the glycone and aglycone portions can be chemically separated by hydrolysis in the presence of acid and can be ... then the molecule is a glucuronide; etc. In the body, toxic substances are often bonded to glucuronic acid to increase their ...
Ellagic acid itself results from the hydrolysis of ellagitannins in the gut in the presence of water.[citation needed] Sources ... Urolithin A and its derivatives - urolithin A glucuronide and urolithin A sulfate being most abundant - release into the ...
A more important fate may be hydrolysis. Carbophenothion can be synthesized in two steps from 4-chlorothiophenol, hydrogen ... This is then converted in approximately equal proportions to sulphate and glucuronide conjugates. Furthermore, there are ...
The main metabolite is the inactive hydrolysis product with the ring opened. Ertapenem is mainly eliminated via the kidneys and ... they may reduce enterohepatic circulation and recycling of valproic acid glucuronide by acting against gut bacteria; and they ... they may increase metabolization of valproic acid to its glucuronide; ...
The major metabolites of diamorphine, 6-MAM, morphine, morphine-3-glucuronide, and morphine-6-glucuronide, may be quantitated ... Furthermore, some testing procedures employ a hydrolysis step before quantitation that converts many of the metabolic products ... a selective heroin/morphine-6β-glucuronide antagonist". FEBS Letters. 412 (1): 35-8. doi:10.1016/S0014-5793(97)00710-2. PMID ... that 6-MAM binds to a subtype of μ-opioid receptors that are also activated by the morphine metabolite morphine-6β-glucuronide ...
Human β-glucuronidase is a type of glucuronidase (a member of glycosidase Family 2) that catalyzes hydrolysis of β-D-glucuronic ... in water sources and comparison with the expression of beta-glucuronidase activity in 4-methylumbelliferyl-beta-D-glucuronide ... Using analysis of labeled β-glucuronidase peptides after hydrolysis of a substrate that enters a very stable intermediate stage ... This homologous relationship, along with the knowledge that glycosidases often perform hydrolysis catalyzed by two acidic ...
Some of the water-soluble conjugates are excreted via the bile duct, and partly reabsorbed after hydrolysis from the intestinal ... Estradiol is excreted in the form of glucuronide and sulfate estrogen conjugates in urine. ... estradiol glucuronide and, as such, excreted via the kidneys. ...
Partial hydrolysis of diethyl 3,4-furandicarboxylate (I) with an equimolar quantity of NaOH results in the monoester 4-( ... Out of all the metabolites found in urine, the primary excretion pathway, 4-IPO glucuronide was the most abundant. Excretion of ... forming 4-IPO glucuronide. This can, like the NAL/NAC-IPO adduct, be excreted. However, the major pathway involves the enedial ... 4-IPO glucuronide can be increased when rats were treated with phenobarbital, which increases γ-aminobutyric acid (GABA) ...
After hydrolysis, retinol is taken up by the enterocytes. Retinyl ester hydrolysis requires the presence of bile salts that ... Walker, JR; Alshafie, G; Abou-Issa, H; Curley, RW (12 September 2002). "An Improved Synthesis of the C-linked Glucuronide of N ... Several enzymes that are present in the intestinal lumen may be involved in the hydrolysis of dietary retinyl esters. ...
The conjugate with the acetyl group intact is referred to as the acyl glucuronide; the deacetylated conjugate is the phenolic ... It is stable in dry air, but gradually hydrolyses in contact with moisture to acetic and salicylic acids. In solution with ... Dogs are better able to tolerate aspirin than cats are.[173] Cats metabolize aspirin slowly because they lack the glucuronide ... Conjugation with glycine forms salicyluric acid, and with glucuronic acid to form two different glucuronide esters. ...
... hydrolysis test[edit]. Aesculin is incorporated into agar with ferric citrate and bile salts (bile aesculin agar).[4] ... Aesculin will fluoresce under long wave ultraviolet light (360 nm) and hydrolysis of aesculin results in loss of this ... National Standard Methods MSOP 48 (Bile aesculin agar) and BSOPTP 2 (Aesculin hydrolysis test (UK)) ... Hydrolysis of aesculin forms aesculetin (6,7-dihydroxycoumarin) and glucose. Aesculetin forms dark brown or black complexes ...
Ester bonds are easily biodegradable through spontaneous or endogenous, nonspecific esterase hydrolysis, which has been ... but they are mostly excreted in urine as glucuronide conjugates. The presence of synthetic cannabinoids or their metabolites in ... in most cases are formed by oxidation of the alkyl side-chain to an alcohol and carboxylic acid followed by glucuronide ...
The hydrolysis under acidic conditions is a reversion of the Fischer-Speier esterification, whereas the hydrolysis under basic ... Nevertheless, metabolites like monobutyl glucuronide and monobenzyl phthalate glucuronide as well as trace amounts of free ...
In humans it is metabolized within 7 hours into trichloroethanol and trichloroethanol glucuronide by erythrocytes and plasma ... 5 HCl In basic conditions the haloform reaction takes place and chloral hydrate is decomposed by hydrolysis to form chloroform ...
beta-Glucuronidase catalyzed hydrolysis of benzo(a)pyrene-3-glucuronide and binding to DNA ... beta-Glucuronidase catalyzed hydrolysis of benzo(a)pyrene-3-glucuronide and binding to DNA ... beta-Glucuronidase catalyzes the hydrolysis of benzo[a]pyrene-3-glucuronide to 3-hydroxybenzo[a]pyrene. During the enzymatic ... beta-Glucuronidase catalyzed hydrolysis of benzo(a)pyrene-3-glucuronide and binding to DNA ...
Enzymatic conjugation and hydrolysis of [18O]isoborneol glucuronide. Message Subject (Your Name) has forwarded a page to you ... Enzymatic conjugation and hydrolysis of [18O]isoborneol glucuronide.. L P Johnson and C Fenselau ... Enzymatic conjugation and hydrolysis of [18O]isoborneol glucuronide.. L P Johnson and C Fenselau ... Enzymatic conjugation and hydrolysis of [18O]isoborneol glucuronide.. L P Johnson and C Fenselau ...
Hydrolysis of iodothyronine glucuronides by obligately anaerobic bacteria isolated from human faecal flora. Publication. ... 35 bacterial strains isolated from the human faecal flora were screened for hydrolysis of the glucuronides of 3,3′,5- ... Hydrolysis of iodothyronine glucuronides by obligately anaerobic bacteria isolated from human faecal flora. F E M S ... Iodothyronine glucuronides, obligate anaerobes Persistent URL. dx.doi.org/10.1016/0378-1097(86)90101-1, hdl.handle.net/1765/ ...
Enzymatic hydrolysis. Each isolated glucuronide was subjected to enzymatic hydrolysis with β-glucuronidase. Surprisingly, two ... Enzymatic hydrolysis. 5 µL aliquots of stock solutions containing ca. 5 mg/L of each isolated (iso-)DON/DOM glucuronide were ... All of these glucuronides escape detection in the conventional methods based on enzymatic hydrolysis and detection of released ... Likewise, iso-DON- and iso-DOM- glucuronides have never been quantified in hydrolysis methods unless iso-DON and iso-DOM ...
Detection and quantitation of drug glucuronides is an essential part of forensic and toxicologic analyses with potential social ... Many drugs are rapidly and extensively metabolized to their glucuronide conjugates for excretion. ... Certification of Reference Materials: Purity Analysis of Morphine-3β-D-Glucuronide by Quantitative NMR, Enzymatic Hydrolysis LC ... Hydrolysis of M3G by glucuronidase enzyme followed by assay using LC-MS/MS traceable to a morphine reference standard; ...
... glucuronidase for the hydrolysis of desomorphine-glucuronide. Both BGTurbo and IMCSzyme offered fast hydrolysis with no need ... Although hydrolysis of conjugated species is sometimes required prior to analysis, desomorphine-glucuronide has not been fully ... each hydrolysis method produced complete hydrolysis (96 percent); however, under simulated challenging conditions, P. vulgata ... Acid hydrolysis was compared with five -glucuronidase sources (BGTurbo, IMCSzyme, Escherichia coli, Helix pomatia and Patella ...
GUSB-Mediated Hydrolysis of Resveratrol Glucuronides.. The hydrolysis potential of resveratrol glucuronides (R3G and R4′G) in ... Two glucuronide isomers [i.e., resveratrol 3-O-glucuronide (R3G) and resveratrol 4′-O-glucuronide (R4′G)] were excreted into ... 2A). Both the control lysate and GUSB lysate were able to catalyze hydrolysis of resveratrol glucuronides (R3G and R4′G) (Fig. ... 2, B and C). As expected, the GUSB lysate showed a much higher hydrolysis activity toward the glucuronides compared with the ...
Metabolism by 3 and 16-beta hydroxylation , glucuronides and sulfates found in urine ...
Two N-oxide metabolites and one glucuronide metabolite were observed. Surprisingly, ester hydrolysis was not a major metabolic ...
Glucuronide hydrolysis. Irinotecan is converted to SN-38-G by the host and converted back into cytotoxic SN-38 in intestine ... Hydrolysis. Conversion to cyanuric acid, which cocrystallizes with melamine in kidneys. Zheng et al., 2013. ... Hydrolysis. Bromovinyluracil produced is metablized by the host to an inhibitor of host dihydropyrimidine dehydrogenase, ... Drug-drug interactions can also arise as a consequence of microbial biotransformations, such as the hydrolysis of the antiviral ...
... hydrolysis of codeine-6-glucuronide in 15 minutes, eliminate 6-MAM > morphine conversion, 2 year shelf life, broad efficacy ... Accelerating Hydrolysis Efficiency. *Greater than 90% hydrolysis of codeine-6-glucuronide in 15 minutes. ... 50 U/μL enzyme in spiked urine at 1000 ng/mL glucuronide (nominal). Enzyme used as supplied (pH 5.0). 70 °C hydrolysis ... Optimize Your Hydrolysis. Ensure accuracy and efficiency of analytical results using glucuronide reference standards for ...
GUS catalyses the hydrolysis of β-glucuronides and, less efficiently, some β-galacturonides. E. coli lives in the digestive ... 1986), and the GUS enzyme enables it to metabolise β-glucuronides as a main source of carbon and energy. 56. The uidA gene is ... the cell-wall hydrolysis enzymes needed for conversion of cellulose (a complex carbohydrate) to fermentable sugars such as ...
Metabolism and elimination: In vitro and in vivo, clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative. ... In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed. ... The two structures at the bottom are tautomers of each other; and the final step is a hydrolysis. The active metabolite (top ...
This latter compound would result from reductive deiodination and amide hydrolysis of closantel. No sulfate or glucuronide ... The scheme shown in Figure 2 would, therefore, apply to rats, with the possibility of amide hydrolysis occurring after the ...
Kamata T, Nishikawa M, Katagi M, Tsuchihashi H (2003). "Optimized glucuronide hydrolysis for the detection of psilocin in human ... Some psilocin is not broken down by enzymes and instead forms a glucuronide; this is a biochemical mechanism animals use to ...
Sulfates and glucuronides were present in urine in similar proportions before ovulation in the marmoset, although after ... The results compared well with those for total estradiol 17-beta after hydrolysis and ether extraction. The use of direct ... Conversely, most of the estrogens in tamarin urine appear to be conjugated as glucuronides. Direct assay for estrone sulfate ...
Both are glucuronides based on hydrolysis studies using sulfatase-free glucuronidases. On the other hand, formononetin was ... Wilkinson AP, Gee JM, Dupont MS, Needs PW, Mellon FA, Williamson G, and Johnson IT (2003) Hydrolysis by lactase phlorizin ... Conversion of Biochanin A to Genistein. Daidzein and genistein were found in bile after their hydrolysis with β-glucuronidase ... The relationship between the peak areas of the metabolites before hydrolysis and the peak areas of aglycones after the ...
Include hydration of epoxides and arene oxides, hydrolysis of Sulfonylureas, Carbamates, Hydroxamates and alpha Glucuronide and ... Glucuronide Conjugation formation of hydrazo intermediate which undergo cleavage at N-N bond. *Very important Synthetic ... Glucuronide formation occurs in 2 steps:- formation of hydrazo intermediate which undergo cleavage at N-N bond. ... Hydrolysis of amides: formation of hydrazo intermediate which undergo cleavage at N-N bond. ...
8-dihydronormorphine-3-glucuronide. The base portion of both metabolites was liberated by acid hydrolysis and isolated. ... ISOLATION OF TWO DIFFERENT GLUCURONIDE METABOLITES OF NALOXONE FROM THE URINE OF RABBIT AND CHICKEN. JAMES M. FUJIMOTO ... ISOLATION OF TWO DIFFERENT GLUCURONIDE METABOLITES OF NALOXONE FROM THE URINE OF RABBIT AND CHICKEN. JAMES M. FUJIMOTO ... ISOLATION OF TWO DIFFERENT GLUCURONIDE METABOLITES OF NALOXONE FROM THE URINE OF RABBIT AND CHICKEN. JAMES M. FUJIMOTO ...
The scutellarin (Scutellarein-7-glucuronide) is transformed by hydrolysis into scutellarein. UmiKalsom, Yusuf; Harborne, ...
Also noted are several 8-hydroxyflavonoid glucuronides; gossypetin 3-glucoside 8-glucuronide, and hypolaetin 8-glucuronide. The ... Constituents/Active Ingredients: 8-10% mucilage, which on hydrolysis produces arabinose, glucose, rhamnose, galactose, and ...
For each RIA, a hydrolysis step was included to remove sulfate and glucuronide residues. The estrogen metabolites were then ... The enzymatic hydrolysis step removed sulfate and glucuronide residues from estrogen metabolites. Using one 0.5 mL urine sample ... Details of the analytic method for urinary estrogen metabolites, which includes hydrolysis, extraction, derivatization, and LC- ... the ELISA methods also included a hydrolysis step before measuring estrogen metabolites. The measurement of 2-OHE1 and 16α-OHE1 ...
A few minor additional metabolites were detected in urine, which appeared to be acyl-glucuronides of CGP 47292. There is no ... Most elimination of rufinamide is via metabolism, with the primary metabolite resulting from enzymatic hydrolysis of the ... The primary biotransformation pathway is carboxylesterase(s) mediated hydrolysis of the carboxamide group to the acid ...
Incomplete recovery of prescription opioids in urine using enzymatic hydrolysis of glucuronide metabolites. J Anal Toxicol. ... hydromorphone-glucuronide, and morphine-6-glucuronide, supporting the ability to accurately identify and quantify all compounds ... Enzymatic hydrolysis and sample pretreatment are performed in the wells of the extraction plate, mini-mizing transfer steps. ... Yet the use of the ACQUITY UPLC BEH Phenyl Column also enables the resolution and analysis of morphine-3-glucuronide and ...
β-glucuronidase hydrolysis (B) was used to confirm that the products observed were indeed glucuronides. The compounds evaluated ... After 2 h of β-glucuronidase hydrolysis, the radioactivity in the region corresponding to the glucuronide for each substrate ... After 2 h of β-glucuronidase hydrolysis, the radioactivity in the region corresponding to the glucuronides was markedly ... β-glucuronidase hydrolysis was used to confirm that the products observed were indeed glucuronides. Fig. 7B ⇓ shows the ...
β-glucuronidase hydrolysis (B) was used to confirm that the products observed were indeed glucuronides. The compounds evaluated ... After 2 h of β-glucuronidase hydrolysis, the radioactivity in the region corresponding to the glucuronide for each substrate ... After 2 h of β-glucuronidase hydrolysis, the radioactivity in the region corresponding to the glucuronides was markedly ... β-glucuronidase hydrolysis was used to confirm that the products observed were indeed glucuronides. Fig. 7B ⇓ shows the ...
Benazepril is extensively metabolized to form benazeprilat as the main metabolite, which occurs by enzymatic hydrolysis, mainly ... Two minor metabolites are the acyl glucuronide conjugates of benazepril and benazeprilat. ...
Dabigatran is metabolized to four different acyl glucuronides and both the glucuronides and dabigatran have similar ... The cleavage of the dabigatran etexilate by esterase-catalyzed hydrolysis to the active principal dabigatran is the predominant ... Dabigatran is subject to conjugation forming pharmacologically active acyl glucuronides. Four positional isomers, 1-O, 2-O, 3-O ... Pharmacokinetics described here refer to the sum of dabigatran and its glucuronides. Dabigatran displays dose-proportional ...
... anomerisation and hydrolysis of acyl glucuronides and glucosides. As previously reported,9,30 the glucosides and glucuronides ... Table 2 Kinetic models for the acyl migration, anomerisation and hydrolysis reactions of the acyl glucuronides of (R)-MPA, (S)- ... Table 3 Degradation rate constants, half-lives and % hydrolysis for the 1-β anomers of acyl glucuronides and acyl glucosides. ... Table 4 Average rate constants (h−1) for acyl migration, anomerisation and hydrolysis of acyl glucuronides and glucosides ...
  • During the enzymatic hydrolysis, a benzo[a]pyrene derivative is formed which binds to DNA to a far greater extent than either the 3-hydroxybenzo[a]pyrene or its glucuronide. (sciencemag.org)
  • Mass-spectrometric analysis of 18O enrichment in both the aglycon and the intact conjugate made it possible to study both enzymatic conjugation and enzymatic hydrolysis. (aspetjournals.org)
  • Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. (springer.com)
  • Deconjugation efficiencies using chemical and enzymatic hydrolysis were evaluated and stability in aqueous solution was assessed. (ojp.gov)
  • All sample preparation steps, including enzymatic hydrolysis, are performed within the wells of the micro-elution plates, and the extraction method is simplified, eliminating conditioning and equilibration steps, and consolidating the wash procedures into a single step. (waters.com)
  • After enzymatic hydrolysis and thin-layer chromatography, 85% of the activity was found in a single spot corresponding to 5 HBC. (inchem.org)
  • Circulating conjugates (glucuronides/sulfates) of FMN and it?s metabolite daidzein (DZN) were quantified using enzymatic hydrolysis of plasma samples. (omicsonline.org)
  • Therefore an enzymatic hydrolysis should be the first step in analysis. (semanticscholar.org)
  • Enzymatic hydrolysis procedures can be time-consuming, with hydrolysis incubation times ranging from 15 minutes to more than 24 hours. (aacc.org)
  • Although chemical hydrolysis is faster than enzymatic hydrolysis, acid can degrade benzodiazepine and opioid drugs, too, which may hinder accurate drug identification. (aacc.org)
  • Enzymatic hydrolysis varies in its effectiveness depending on the drug and the enzyme [2]. (chromsystems.com)
  • Two N -oxide metabolites and one glucuronide metabolite were observed. (springer.com)
  • The base portion of both metabolites was liberated by acid hydrolysis and isolated. (aspetjournals.org)
  • Acyl glucuronide metabolites have been implicated in the toxicity of several carboxylic acid-containing drugs, and the rate of their degradation via intramolecular transacylation and hydrolysis has been associated with the degree of protein adduct formation. (rsc.org)
  • Whilst glucuronides are common metabolites of xenobiotics, there are relatively few well-documented examples of glucose conjugates (glucosides) of xenobiotics in the literature ( e.g. see Meech et al. (rsc.org)
  • It also allows monitoring of the metabolites of these glucuronides. (waters.com)
  • For both compounds, ester hydrolysis and ester hydrolysis in combination with oxidative defluorination were the most prevalent metabolites produced in vitro. (nih.gov)
  • Approximately 20% of the administered dose was excreted as the sulfate and glucuronide conjugates of hydroxylated metabolites. (inchem.org)
  • A few minor additional metabolites were detected in urine, which appeared to be acyl-glucuronides of CGP 47292. (drugbank.ca)
  • It suggests that the glucuronide/sulfate conjugates are major circulating metabolites in blood. (omicsonline.org)
  • This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides) and its metabolites. (cdc.gov)
  • Abstract The effective analysis of anabolic‐androgenic steroids in urine usually requires a suitable deconjugation method for the analysis of phase II metabolites such as sulphates and glucuronides. (separationsnow.com)
  • Absorbed monoester metabolites are usually oxidized in the body and, in humans, excreted in urine largely as glucuronide conjugates (Albro et al. (cdc.gov)
  • The monoester metabolites are thought to mediate toxic effects for some of the phthalates, but there are known species-related differences in the hydrolysis of diester phthalates, efficiency of intestinal absorption, and extent of metabolite conjugation to glucuronide (Albro et al. (cdc.gov)
  • Many carboxylic acid-containing drugs are associated with idiosyncratic drug toxicity (IDT), which may be caused by reactive acyl glucuronide metabolites. (bireme.br)
  • Here, 13 drugs with a carboxylic acid moiety were incubated with human liver microsomes to produce acyl glucuronide conjugates for the determination of acyl glucuronide half-lives by acyl migration and with HepaRG cells to monitor the formation of acyl CoA conjugates, their further conjugate metabolites, and trans-acylation products with glutathione. (bireme.br)
  • On the basis of the results, the short relative half-life of the acyl glucuronide (high acyl migration rate), high daily dose and detection of acyl CoA conjugates, or further metabolites derived from acyl CoA together seem to indicate that carboxylic acid-containing drugs have a higher probability to cause drug-induced liver injury (DILI). (bireme.br)
  • Five metabolites were detected and tentatively identified, which suggested that the major metabolic pathways of Pyragrel in human were double-bond reduction, double-bond oxidation, and then followed by glucuronide conjugation. (mdpi.com)
  • Two main metabolites were then prepared using β-glucuronide hydrolysis and macroporous resin purification approach followed by preparative high-performance liquid chromatography (PHPLC) method, with their structures confirmed on the basis of nuclear magnetic resonance (NMR) data. (mdpi.com)
  • In particular, studies have shown that immunoassay drug screens for benzodiazepines and opioids produce false negative results due to poor analyte cross-reactivity with various glucuronide metabolites. (aacc.org)
  • One potential solution is to cleave conjugated metabolites prior to analysis using hydrolysis, which increases the parent drug concentration of therapeutics that are primarily metabolized to glucuronide or sulfate metabolites. (aacc.org)
  • Lastly, hydrolysis procedures may not produce 100% cleavage of the conjugated metabolites and the efficiency of various enzymatic and acid protocols varies between different drugs. (aacc.org)
  • As an alternative to preanalytical hydrolysis, laboratories can select analytical methods with higher sensitivity to afford analyte detection at lower cutoffs and/or the ability to detect glucuronide metabolites. (aacc.org)
  • So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. (springer.com)
  • The metabolite from the rabbit was naloxone-3-glucuronide and that from the chicken was N-allyl-14-hydroxy-7,8-dihydronormorphine-3-glucuronide. (aspetjournals.org)
  • Together, these models may find application in drug discovery for prediction of acyl glucuronide and glucoside metabolite behaviour. (rsc.org)
  • 7 However, a large fraction of SN-38 is further metabolized in the liver by members of the UDP-glucuronosyltransferase 1A family to the inactive glucuronide metabolite (SN-38G). (nature.com)
  • The major metabolite was methyl-5 hydroxy 2-benzimidazolecarbamate (5 HBC) which was present in the urine as the glucuronide and/or sulfate. (inchem.org)
  • Compounds found in urine included 2-dimethylamine-thiazolidine carboxylic acid (M1) and the S-glucuronide of dimethyldithiocarbamic acid and an unknown metabolite of apparent mass 326. (europa.eu)
  • Metabolism by carboxyesterases into inactive metabolite CGP 47292, a carboxylic acid derivative, via hydrolysis is the primary biotransformation pathway. (drugbank.ca)
  • The metabolite Genistein (GEN), GEN and BCA conjugates (glucuronides and/or sulfates) were detected from first time point onward. (omicsonline.org)
  • Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring. (bmj.com)
  • Urine samples from workers exposed to 4,4'-methylenebis (2-chloroaniline) (MbOCA) contain a labile metabolite(s) that, on hydrolysis, yields the parent compound at concentrations two to three times those of free MbOCA. (bmj.com)
  • Evidence has now been obtained that the major labile metabolite is an N-glucuronide of MbOCA. (bmj.com)
  • This product, the chemically synthesised glucuronide, and the labile urinary metabolite had identical chromatographic and hydrolytic (heat and beta-glucuronidase) properties. (bmj.com)
  • Another limitation of acid hydrolysis is that the heroin metabolite 6-mono-acetylmorphine (6-AM) is de-acetylated and converted to morphine during the process, which impedes the ability to detect heroin use from the presence of 6-AM in urine. (aacc.org)
  • Many drugs are rapidly and extensively metabolized to their glucuronide conjugates for excretion. (sigmaaldrich.com)
  • our findings suggest that the charged carboxylate ion and neutral hydroxyl group in the glucuronide and glucoside conjugates, respectively, are responsible for these differences. (rsc.org)
  • The reactivity of the acyl glucuronide conjugates of drugs and other xenobiotics has been studied extensively on account of their potential hepatotoxicity 1-4 (as have the corresponding S -acyl-CoA thioesters which are also chemically reactive). (rsc.org)
  • These metabolic conjugates are subject to biliary secretion into the intestine where they undergo gut hydrolysis and reabsorbtion thus increasing the exposure of the drug. (waters.com)
  • ABCC1, also known as MRP1 (multidrug resistance-associated protein), is an ATP-dependent transporter that provides the energy for the movement of GSH, glucuronide, and sulfate conjugates, across membranes. (jax.org)
  • Enzymatic conjugation and hydrolysis of [18O]isoborneol glucuronide. (aspetjournals.org)
  • Introduction of 18O into the acetal linkage of isoborneol glucuronide has been accomplished through the in vitro enzymatic conjugation of 18O-labeled isoborneol by use of immobilized, partially purified, rabbit liver UDP-glucuronyltransferase supplemented with UDP-glucuronic acid. (aspetjournals.org)
  • Analysis by gas chromatography-mass spectrometry indicated that the labeled hydroxyl oxygen of isoborneol is retained during both conjugation and hydrolysis. (aspetjournals.org)
  • Similar to other opioids, during phase II metabolism it undergoes conjugation with glucuronic acid to form desomorphine-glucuronide. (ojp.gov)
  • 5-8 Acyl glucuronides are formed through the conjugation of α- D -glucuronic acid with the carboxylic acid group of a xenobiotic in the presence of membrane-bound UDP-glucuronosyltransferase (UGT) enzymes. (rsc.org)
  • Estradiol is also metabolized via sulphate and glucuronide conjugation, which in turn undergoes enterohepatic recirculation in the liver. (waters.com)
  • Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. (springer.com)
  • The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of the currently used methods for DON-biomarker analysis. (springer.com)
  • Benzoic acid can be further metabolised to hippuric acid and benzoyl glucuronide and excreted in the urine. (europa.eu)
  • These studies show that the major labile conjugate of MbOCA in the urine of workers exposed to this compound is probably the mono N-glucuronide. (bmj.com)
  • In view of the lability of this compound and the fact that its concentration in urine is two to three times that of free MbOCA, it is essential that any strategy for the biological monitoring of exposed workers takes into account the N-glucuronide. (bmj.com)
  • Surprisingly, ester hydrolysis was not a major metabolic pathway for carfentanil. (springer.com)
  • Additionally, the conversion of ester hydrolysis with oxidative defluorination to pentanoic acid for the first time was identified for 5F-MDMB-PICA. (nih.gov)
  • and two by ester hydrolysis. (inchem.org)
  • Enzyme hydrolysis assay is an indirect method of analysis. (sigmaaldrich.com)
  • The hydrolysis of glucuronides can be catalysed by beta-glucuronidase, an enzyme expressed in many tissues and body fluids in humans. (nih.gov)
  • The possible contribution of beta-glucuronidase to drug disposition in humans has not been assessed in a systematic manner, but this enzyme may be able to release, locally or systemically, the active or inactive parent compound from drug glucuronides, thereby modifying the disposition and action of these drugs. (nih.gov)
  • Hydrolysis of testosterone 17-sulfate to testosterone by the P. aeruginosa arylsulfatase and a cartoon of the sulfatase (PDB 1HDH) looking into the enzyme active site. (edu.au)
  • Vmax (range: 0.735-24.012 µmol·min-1·unit-1 [1 unit is defined as the release of 1 µM 4-methylumbelliferyl-ß-D-glucuronide per min]) and the reaction rate constants at low substrate concentrations (k) (range: 0.002-0.062 min-1·(unit/L)-1 were similar for all substrates-enzyme combinations tested. (wur.nl)
  • Many plants store chemicals in the form of inactive glycosides, which can be activated by enzyme hydrolysis. (naturalmedicinejournal.com)
  • Hydrolysis can be mediated via an enzyme reaction with β-glucuronidase or chemically with hydrochloric acid or sodium hydroxide base. (aacc.org)
  • This has been achieved by using a carefully selected enzyme that ensures a complete and selective hydrolysis of all 106 drugs that are covered in the assay, including codeine. (chromsystems.com)
  • A new response test where retinoyl beta-glucuronide is administered and the degree of hydrolysis to retinoic acid is measured has been investigated. (nih.gov)
  • The degree of hydrolysis (α) can be used as a quantitative characteristic for the hydrolysis of salts. (thefreedictionary.com)
  • Since some issues surrounding the beta-glucuronidase-mediated deconjugation of drug glucuronides still need to be clarified in humans, additional data from animal models supporting this concept have been included. (nih.gov)
  • Acid hydrolysis using methanolysis is one adopted method of deconjugation that efficiently and rapidly cleaves both sulphates and glucuronides contemporaneously. (separationsnow.com)
  • We have studied deconjugation kinetics and pH optimum for four sources of ß-glucuronidase (human neutrophil, human recombinant, myeloid PLB-985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3-glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7-glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-ß-D-glucuronide, and para-nitrophenol-glucuronide. (wur.nl)
  • At inflammatory sites in vivo the pH, neutrophil and flavonoid glucuronide concentrations seem favorable for deconjugation. (wur.nl)
  • Erratic quality assurance results for codeine - one of the more difficult to hydrolyse compounds - are considered to be based on an incomplete hydrolysis [3]. (chromsystems.com)
  • Resveratrol undergoes extensive metabolism to form biologically active glucuronides in humans. (aspetjournals.org)
  • A cellular pharmacokinetic model integrating resveratrol transport/metabolism with glucuronide hydrolysis/excretion was well fitted to the experimental data, allowing derivation of the efflux rate constant values in the absence or presence of shRNA targeting MRP4. (aspetjournals.org)
  • Important reactions of drug metabolism, including UGT mediated glucuronidation and steroidsulfatase mediated hydrolysis of sulfates, take place in the endoplasmic reticulum (ER) of hepatocytes. (uzh.ch)
  • Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. (wur.nl)
  • Hydrolysis is an important reaction in plants and animals (see metabolism metabolism, sum of all biochemical processes involved in life. (thefreedictionary.com)
  • 19 Expression of secreted βG at cancer cells can effectively activate glucuronide prodrugs, but leakage from the tumor microenvironment may allow systemic activation of prodrugs that produces adverse effects. (nature.com)
  • 20 A more selective approach to activate glucuronide prodrugs is to anchor βG on the membrane of tumor cells. (nature.com)
  • Moreover, as beta-glucuronidase has already been proven to be useful in tumour specific bioactivation of glucuronide prodrugs of anticancer agents, we also focus on anticancer prodrug approaches utilising beta-glucuronidase. (nih.gov)
  • Using glucuronide prodrugs for broad-spectrum fluoroquinolone antibacterial agents, we capitalize on this behaviour and perform localized synthesis of antimicrobials which affords a significant zone of inhibition of bacterial growth around the metallic material. (rsc.org)
  • Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. (springer.com)
  • Furthermore, β -glucuronidase expressed in the cells catalyzed the hydrolysis of the glucuronides back to the parent compound. (aspetjournals.org)
  • Acid hydrolysis was compared with five -glucuronidase sources (BGTurbo, IMCSzyme, Escherichia coli, Helix pomatia and Patella vulgata). (ojp.gov)
  • Most drugs are metabolized by phase I reactions that involve oxidation, reduction, and hydrolysis principally involving the CYP450 enzymes. (reference.com)
  • These enzymes modify the drug chemically by processes such as oxidation, reduction and hydrolysis or by the removal and addition of an active group. (reference.com)
  • Here, we aimed to characterize the efflux transport of resveratrol glucuronides using UGT1A1-overexpressing HeLa cells (HeLa1A1 cells), and to determine the contribution of multidrug resistance-associated protein (MRP) 4 to cellular excretion of the glucuronides. (aspetjournals.org)
  • The excretion rate was linearly related to the level of intracellular glucuronide, indicating that glucuronide efflux was a nonsaturable process. (aspetjournals.org)
  • Likewise, short-hairpin RNA (shRNA)-mediated silencing of MRP4 caused a significant reduction in glucuronide excretion but an elevation in glucuronide accumulation. (aspetjournals.org)
  • It was found that a large percentage of glucuronide excretion (43%-46%) was attributed to MRP4. (aspetjournals.org)
  • In conclusion, MRP4 participated in cellular excretion of R3G and R4′G. Integration of mechanistic pharmacokinetic modeling with transporter knockdown was a useful method to derive the contribution percentage of an exporter to overall glucuronide excretion. (aspetjournals.org)
  • The objective of the present study was to determine the role of MRP4 in excretion of resveratrol glucuronides using UGT1A1 stably transfected HeLa cells. (aspetjournals.org)
  • Contribution of MRP4 to glucuronide excretion was quantified by coupling short-hairpin RNA-mediated silencing with mechanistic pharmacokinetic modeling. (aspetjournals.org)
  • Consequently, UGT generated glucuronides, like estradiol-17β-glucuronide, have to be translocated back into the cytoplasm to reach their site of excretion. (uzh.ch)
  • 16 The overall rate of disappearance of the 1-β- O -acyl glucuronide, termed the degradation rate ( k d ) is a combination of (i) the initial rate of acyl migration from the 1-β to the 2-β anomer and (ii) hydrolysis of the 1-β- O -acyl glucuronide. (rsc.org)
  • 19 As a consequence, previous studies have attempted to relate glucuronide acyl migration reaction rates to observed in vivo toxicity. (rsc.org)
  • The rate of acyl migration has been earlier suggested as a predictor of acyl glucuronide reactivity. (bireme.br)
  • Correlation between half-lives and toxicity classification increased when "relative half-lives," taking into account the formation of isomeric AG-forms due to acyl migration and eliminating the effect of hydrolysis, were used instead of plain disappearance of the initial 1-O- -AG-form. (bireme.br)
  • Glucuronidation is typically considered to be a detoxification process that aids the elimination of xenobiotics from the body, but it is possible for the positional anomers of acyl glucuronides to irreversibly bind to endogenous proteins, a process that is thought to potentiate toxicity. (rsc.org)
  • In the human body, many drugs undergo glucuronidation, which requires an enzymatic or acidic hydrolysis prior to the analysis - a challenge for many assays. (chromsystems.com)
  • 12 - 14 Both buprenorphine and norbuprenorphine undergo glucuronidation by UDP-glucuronosyl transferases (UGT) to buprenorphine-3-glucuronide (B3G) and norbuprenorphine-3-glucuronide (N3G). (asahq.org)
  • The levels of isoflavone glucuronides/sulfates were found to be much greater than that of the corresponding aglycones. (omicsonline.org)
  • Despite the emerging importance of steroid sulfates in drug detection there are no generally accepted methods for the hydrolysis of steroid sulfates, which is required prior to employing many methods of analysis. (edu.au)
  • 2015 , 00 , 0000 see here ), we discovered that the arylsulfatase from Pseudomonas aeruginosa serves as a catalyst for the mild hydrolysis of a range of steroid sulfates (Commonwealth of Australia, Anti-Doping Research Program). (edu.au)
  • Also steroidsulfatase substrates, including estrone-3-sulfate, have to cross the ER membrane to reach their site of hydrolysis. (uzh.ch)
  • In conclusion, we show that ß-glucuronidase from four different sources, including human neutrophils, is able to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly similar kinetic rates. (wur.nl)
  • In addition to the well-known differentiation potential of the hydrolysis of 4-MU-beta-D-galactopyranoside, 4-MU-beta-D-glucuronide, and 4-MU-beta-D-xylopyranoside, the hydrolysis of some other fluorogenic substrates (e.g., 4-MU-beta-D-fucopyranoside, 4-MU-N-acetyl-beta-D-galactosaminide, and 4-MU-alpha-D-galactopyranoside) can also be used for species differentiation within the family Enterobacteriaceae. (asm.org)
  • Here we report detailed kinetic models of each transacylation and hydrolysis reaction for a series of phenylacetic acid acyl glucuronides and their analogous acyl glucosides. (rsc.org)
  • Some industrially important hydrolysis reactions are the synthesis of alcohols from olefins (e.g., ethanol, CH 3 COOH, from ethene, CH 2 CH 2 ) in the presence of a strong acid catalyst, the conversion of starches to sugars in the presence of a strong acid catalyst, and the conversion of animal fats or vegetable oils to glycerol and fatty acids by reaction with steam. (thefreedictionary.com)
  • Consequently, some papers recommend the use of an acidic hydrolysis, however, this can degrade both opioids and other substances [4]. (chromsystems.com)
  • We demonstrated the ability of human liver microsomes to convert flavopiridol to its corresponding glucuronide (20) , providing evidence for existence of this metabolic pathway in humans as well. (aacrjournals.org)
  • Detection and quantitation of drug glucuronides is an essential part of forensic and toxicologic analyses with potential social, legal and clinical significance. (sigmaaldrich.com)
  • This Certified Spiking Solution ® provides added value in allowing for quantitation of androsterone glucuronide levels by LC-MS/MS without the need for hydrolysis. (cerilliant.com)
  • The N-glucuronide of MbOCA was synthesised chemically, characterised by thermospray mass spectrometry, and found to have a pseudomolecular (M + 1) ion at m/z 443/445. (bmj.com)
  • In addition, after hydrolysis, impurities were investigated by LCMS to ensure that M3G hydrolyzed exclusively to morphine in the assay analysis. (sigmaaldrich.com)
  • The sample prep for the amount they routinely deal with usually takes 6 hours (excluding hydrolysis), but by using the commercial assay, the lab was able to reduce the time down to 2 hours. (chromsystems.com)
  • Phase II glucuronides were identified in 5F-MDMB-PICA (n = 3) and 5F-MDMB-PINACA (n = 5). (nih.gov)
  • For estradiol-17β-glucuronide a fast time-dependent efflux with similar efficiencies from SER and RER but no clear protein-mediated uptake was shown, indicating an asymmetric transport system for this substrate. (uzh.ch)
  • Ensure accuracy and efficiency of analytical results using glucuronide reference standards for hydrolysis controls. (sigmaaldrich.com)
  • Although not yet proven, the formation of protein adducts in vivo - and subsequent downstream effects - has been proposed as a mechanism of toxicity for carboxylic acid-containing xenobiotics capable of forming acyl glucuronides. (rsc.org)
  • Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. (wur.nl)
  • Hydrolysis Cleavage of a xenobiotic by the addition of water. (powershow.com)
  • When choosing a method, labs should assess whether hydrolysis increases detection of the parent drug concentration above the analytical cutoff and whether it improves analytical sensitivity in comparison with approaches that use non-hydrolyzed samples. (aacc.org)
  • However, SN-38 is rapidly metabolized to the inactive SN-38 glucuronide (SN-38G) in the liver, which reduces the amount of SN-38 available for killing cancer cells. (nature.com)
  • Two glucuronide isomers [i.e., resveratrol 3- O -glucuronide (R3G) and resveratrol 4′- O -glucuronide (R4′G)] were excreted into the extracellular compartment after incubation of resveratrol (1-100 μ M) with HeLa1A1 cells. (aspetjournals.org)
  • Detoxification proceeded primarily through two major routes, hydroxylation and hydrolysis. (inchem.org)
  • At pH 4, the Km ranged 44-fold from 22 µM for quercetin-4'-glucuronide with Helix pomatia ß-glucuronidase, to 981 µM for para-nitrophenol-glucuronide with recombinant ß-glucuronidase. (wur.nl)
  • No degradation was observed for either desomorphine or desomorphine-glucuronide under any of the conditions tested. (ojp.gov)
  • Glucuronides of drugs often accumulate during long term therapy. (nih.gov)
  • Clearly, longer acyl glucuronide half-lives were observed for safe drugs compared to drugs that can cause IDT. (bireme.br)
  • The current study aims to investigate the transport of taurocholate, estradiol-17β-glucuronide, and estrone-3-sulfate in smooth (SER) and rough (RER) endoplasmic reticulum membrane vesicles isolated from Wistar and TR(-) rat liver. (uzh.ch)
  • Inhibition of steroidsulfatase mediated estrone-3-sulfate hydrolysis decreased estrone-3-sulfate uptake but had no effect on taurocholate or estradiol-17β-glucuronide transport. (uzh.ch)
  • Based on inhibition studies and transport characteristics, three different transport mechanisms are suggested to be involved in the transport of taurocholate, estrone-3-sulfate and estradiol-17β-glucuronide across the ER membrane. (uzh.ch)
  • 21 , 22 We have previously found that tumor-located expression of membrane-tethered βG greatly sensitized tumor cells to a glucuronide produg of p-hydroxyaniline mustard and produced strong antitumor activity in vivo . (nature.com)
  • High intralysosomal [H + ] (about 100x higher than in cytoplasm) is maintained by vacuolar H + , V-type ATPase, located in the lysosomal membrane, which uses the energy of ATP hydrolysis to pump protons into lysosomes [ 1 - 3 ]. (intechopen.com)
  • If insoluble or readily volatile substances are formed by hydrolysis, there is virtually complete decomposition of the initial salt. (thefreedictionary.com)
  • Although hydrolysis of conjugated species is sometimes required prior to analysis, desomorphine-glucuronide has not been fully investigated, so this study optimized and evaluated six hydrolysis procedures. (ojp.gov)
  • Both BGTurbo and IMCSzyme offered fast hydrolysis with no need for sample cleanup prior to liquid chromatography-quadrupole/time of flight-mass spectrometry (LC-Q/TOF-MS) analysis. (ojp.gov)
  • Yet the use of the ACQUITY UPLC BEH Phenyl Column also enables the resolution and analysis of morphine-3-glucuronide and morphine-6-glucuronide, allowing the method's use for direct analysis without hydrolysis. (waters.com)
  • comparative evaluation of different approaches to certification of drug reference materials was performed using Morphine-3β-D-glucuronide (M3G) as an example. (sigmaaldrich.com)
  • Why should drug testing labs consider performing preanalytical hydrolysis? (aacc.org)
  • 3,15,17,18 It has been proposed that the k d of the 1-β- O -acyl glucuronide is related to the incidence of protein binding, and hence potential toxicity. (rsc.org)
  • In general, hydrolysis is represented by the equation A-B + H-OH ⇄ A-H + B-OH, where A-B is the substance undergoing hydrolysis, and A-H and B-OH are the products of hydrolysis. (thefreedictionary.com)
  • Since the antibody used in this test system also recognizes chloramphenicol-glucuronide, this substance can be analyzed without prior hydrolysis. (elisa-tek.com)
  • however, under simulated challenging conditions, P. vulgata was the most efficient -glucuronidase for the hydrolysis of desomorphine-glucuronide. (ojp.gov)
  • 16 , 17 Based on molar area under the plasma concentration versus time curves, glucuronides constitute 70% of a buprenorphine dose. (asahq.org)