Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.DNA (Cytosine-5-)-Methyltransferase: An enzyme that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA.Methyltransferases: A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.Catechol 2,3-Dioxygenase: Catalyzes the oxidation of catechol to 2-hydroxymuconate semialdehyde in the carbazole and BENZOATE degradation via HYDROXYLATION pathways. It also catalyzes the conversion of 3-methylcatechol to cis, cis-2-hydroxy-6-oxohept-2,4-dienoate in the TOLUENE and XYLENE degradation pathway. This enzyme was formerly characterized as EC 1.13.1.2.Estrogens, Catechol: 2- or 4-Hydroxyestrogens. Substances that are physiologically active in mammals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an estrogenic action or interaction with the catecholaminergic system.Catechol 1,2-Dioxygenase: An enzyme that catalyzes the oxidation of catechol to muconic acid with the use of Fe3+ as a cofactor. This enzyme was formerly characterized as EC 1.13.1.1 and EC 1.99.2.2.O(6)-Methylguanine-DNA Methyltransferase: An enzyme that transfers methyl groups from O(6)-methylguanine, and other methylated moieties of DNA, to a cysteine residue in itself, thus repairing alkylated DNA in a single-step reaction. EC 2.1.1.63.Protein Methyltransferases: Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)Histone-Lysine N-Methyltransferase: An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC 2.1.1.43.Catechol O-Methyltransferase: Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.tRNA Methyltransferases: Enzymes that catalyze the S-adenosyl-L-methionine-dependent methylation of ribonucleotide bases within a transfer RNA molecule. EC 2.1.1.S-Adenosylmethionine: Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed)Protein-Arginine N-Methyltransferases: Enzymes that catalyze the methylation of arginine residues of proteins to yield N-mono- and N,N-dimethylarginine. This enzyme is found in many organs, primarily brain and spleen.DNA-Cytosine Methylases: Methylases that are specific for CYTOSINE residues found on DNA.Protein D-Aspartate-L-Isoaspartate Methyltransferase: A PROTEIN O-METHYLTRANSFERASE that recognizes and catalyzes the methyl esterification of ISOASPARTIC ACID and D-ASPARTIC ACID residues in peptides and proteins. It initiates the repair of proteins damaged by the spontaneous decomposition of normal L-aspartic acid and L-asparagine residues.DNA Modification Methylases: Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.Dioxygenases: Non-heme iron-containing enzymes that incorporate two atoms of OXYGEN into the substrate. They are important in biosynthesis of FLAVONOIDS; GIBBERELLINS; and HYOSCYAMINE; and for degradation of AROMATIC HYDROCARBONS.Site-Specific DNA-Methyltransferase (Adenine-Specific): An enzyme responsible for producing a species-characteristic methylation pattern on adenine residues in a specific short base sequence in the host cell DNA. The enzyme catalyzes the methylation of DNA adenine in the presence of S-adenosyl-L-methionine to form DNA containing 6-methylaminopurine and S-adenosyl-L-homocysteine. EC 2.1.1.72.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Oxygenases: Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.Catechol Oxidase: An enzyme of the oxidoreductase class that catalyzes the reaction between catechol and oxygen to yield benzoquinone and water. It is a complex of copper-containing proteins that acts also on a variety of substituted catechols. EC 1.10.3.1.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Protein O-Methyltransferase: An enzyme that catalyzes the transfer of methyl groups from S-adenosylmethionine to free carboxyl groups of a protein molecule forming methyl esters. EC 2.1.1.-.Phosphatidyl-N-Methylethanolamine N-Methyltransferase: An enzyme that catalyzes the METHYLATION of phosphatidyl-N-methylethanolamine to produce phosphatidyl-N-dimethylethanolamine. This enzyme can also methylate phosphatidyl-N-dimethylethanolamine to produce phosphatidyl-N-trimethylethanolamine (PHOSPHATIDYLCHOLINE).Escherichia coli O157: A verocytotoxin-producing serogroup belonging to the O subfamily of Escherichia coli which has been shown to cause severe food-borne disease. A strain from this serogroup, serotype H7, which produces SHIGA TOXINS, has been linked to human disease outbreaks resulting from contamination of foods by E. coli O157 from bovine origin.Phenol: An antiseptic and disinfectant aromatic alcohol.Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Betaine-Homocysteine S-Methyltransferase: A ZINC metalloenzyme that catalyzes the transfer of a methyl group from BETAINE to HOMOCYSTEINE to produce dimethylglycine and METHIONINE, respectively. This enzyme is a member of a family of ZINC-dependent METHYLTRANSFERASES that use THIOLS or selenols as methyl acceptors.Methanosarcina barkeri: A species of halophilic archaea whose organisms are nonmotile. Habitats include freshwater and marine mud, animal-waste lagoons, and the rumens of ungulates.Phosphatidylethanolamine N-Methyltransferase: An enzyme that catalyses three sequential METHYLATION reactions for conversion of phosphatidylethanolamine to PHOSPHATIDYLCHOLINE.Hydroxybenzoates: Benzoate derivatives substituted by one or more hydroxy groups in any position on the benzene ring.Guanidinoacetate N-Methyltransferase: This enzyme catalyzes the last step of CREATINE biosynthesis by catalyzing the METHYLATION of guanidinoacetate to CREATINE.Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants.Polycomb Repressive Complex 2: A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.Sorbic Acid: Mold and yeast inhibitor. Used as a fungistatic agent for foods, especially cheeses.Equilenin: An estrogenic steroid produced by HORSES. It has a total of five double bonds in the A- and B-ring. High concentration of equilenin is found in the URINE of pregnant mares.Corrinoids: Cyclic TETRAPYRROLES based on the corrin skeleton.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Lysine: An essential amino acid. It is often added to animal feed.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Biodegradation, Environmental: Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.Benzoates: Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.Kinetics: The rate dynamics in chemical or physical systems.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.GuaninePseudomonas putida: A species of gram-negative, aerobic bacteria isolated from soil and water as well as clinical specimens. Occasionally it is an opportunistic pathogen.Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid.Genes, Bacterial: The functional hereditary units of BACTERIA.Benzene: Toxic, volatile, flammable liquid hydrocarbon byproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.CpG Islands: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.RNA Caps: Nucleic acid structures found on the 5' end of eukaryotic cellular and viral messenger RNA and some heterogeneous nuclear RNAs. These structures, which are positively charged, protect the above specified RNAs at their termini against attack by phosphatases and other nucleases and promote mRNA function at the level of initiation of translation. Analogs of the RNA caps (RNA CAP ANALOGS), which lack the positive charge, inhibit the initiation of protein synthesis.Bacterial Proteins: Proteins found in any species of bacterium.Phenols: Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.Pyrogallol: A trihydroxybenzene or dihydroxy phenol that can be prepared by heating GALLIC ACID.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.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).Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Dacarbazine: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Antineoplastic Agents, Alkylating: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)Myeloid-Lymphoid Leukemia Protein: Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.Adipates: Derivatives of adipic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,6-carboxy terminated aliphatic structure.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.ChlorobenzenesCresolsHydroquinonesCrystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Toluene: A widely used industrial solvent.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Isoaspartic Acid: An ASPARTIC ACID residue in polypeptide chains that is linked at the beta-carboxyl group instead of at the normal, alpha-carboxyl group, polypeptide linkage. It is a result of the spontaneous decomposition of aspartic acid or ASPARAGINE residues.Hydroxyestrones: Estrone derivatives substituted with one or more hydroxyl groups in any position. They are important metabolites of estrone and other estrogens.Cell Line, Tumor: A cell line derived from cultured tumor cells.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Methyl Chloride: A hydrocarbon used as an industrial solvent. It has been used as an aerosal propellent, as a refrigerant and as a local anesthetic. (From Martindale, The Extra Pharmacopoeia, 31st ed, p1403)5-Methylcytosine: A methylated nucleotide base found in eukaryotic DNA. In ANIMALS, the DNA METHYLATION of CYTOSINE to form 5-methylcytosine is found primarily in the palindromic sequence CpG. In PLANTS, the methylated sequence is CpNpGp, where N can be any base.Deoxyribonucleases, Type II Site-Specific: Enzyme systems containing a single subunit and requiring only magnesium for endonucleolytic activity. The corresponding modification methylases are separate enzymes. The systems recognize specific short DNA sequences and cleave either within, or at a short specific distance from, the recognition sequence to give specific double-stranded fragments with terminal 5'-phosphates. Enzymes from different microorganisms with the same specificity are called isoschizomers. EC 3.1.21.4.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Guanosine: A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)Chlorobenzoates: Benzoic acid or benzoic acid esters substituted with one or more chlorine atoms.DNA Restriction-Modification Enzymes: Systems consisting of two enzymes, a modification methylase and a restriction endonuclease. They are closely related in their specificity and protect the DNA of a given bacterial species. The methylase adds methyl groups to adenine or cytosine residues in the same target sequence that constitutes the restriction enzyme binding site. The methylation renders the target site resistant to restriction, thereby protecting DNA against cleavage.Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.RNA, Transfer: The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.Methanosarcina: A genus of anaerobic, irregular spheroid-shaped METHANOSARCINALES whose organisms are nonmotile. Endospores are not formed. These archaea derive energy via formation of methane from acetate, methanol, mono-, di-, and trimethylamine, and possibly, carbon monoxide. Organisms are isolated from freshwater and marine environments.Homocysteine S-Methyltransferase: An enzyme that catalyzes the demethylation of L-homocysteine to L-METHIONINE.Planococcus Bacteria: A genus of coccoid bacteria in the family PLANOCOCCACEAE. They are widely distributed in various habitats including sea water, freshwater ponds, cyanobacterial mats, and in marine animals.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Methanococcales: An order of anaerobic methanogens in the kingdom EURYARCHAEOTA. They are pseudosarcina, coccoid or sheathed rod-shaped and catabolize methyl groups. The cell wall is composed of protein. The order includes one family, METHANOCOCCACEAE. (From Bergey's Manual of Systemic Bacteriology, 1989)Salicylates: The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.Acinetobacter: A genus of gram-negative bacteria of the family MORAXELLACEAE, found in soil and water and of uncertain pathogenicity.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.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.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Vitamin U: A vitamin found in green vegetables. It is used in the treatment of peptic ulcers, colitis, and gastritis and has an effect on secretory, acid-forming, and enzymatic functions of the intestinal tract.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Histamine N-Methyltransferase: An enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to histamine, forming N-methylhistamine, the major metabolite of histamine in man. EC 2.1.1.8.Chromatin Immunoprecipitation: A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Mesna: A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.Alcaligenes: A genus of gram-negative, aerobic, motile bacteria that occur in water and soil. Some are common inhabitants of the intestinal tract of vertebrates. These bacteria occasionally cause opportunistic infections in humans.Nucleotidyltransferases: A class of enzymes that transfers nucleotidyl residues. EC 2.7.7.Rhodococcus: A bacterial genus of the order ACTINOMYCETALES.Thionucleosides: Nucleosides in which the base moiety is substituted with one or more sulfur atoms.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.Siderophores: Low-molecular-weight compounds produced by microorganisms that aid in the transport and sequestration of ferric iron. (The Encyclopedia of Molecular Biology, 1994)Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.6-Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.Cytidine: A pyrimidine nucleoside that is composed of the base CYTOSINE linked to the five-carbon sugar D-RIBOSE.Pyrococcus abyssi: A species of gram-negative hyperthermophilic ARCHAEA found in deep ocean hydrothermal vents. It is an obligate anaerobe and obligate chemoorganotroph.Monophenol Monooxygenase: An enzyme of the oxidoreductase class that catalyzes the reaction between L-tyrosine, L-dopa, and oxygen to yield L-dopa, dopaquinone, and water. It is a copper protein that acts also on catechols, catalyzing some of the same reactions as CATECHOL OXIDASE. EC 1.14.18.1.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Archaeal Proteins: Proteins found in any species of archaeon.RNA, Ribosomal, 23S: Constituent of 50S subunit of prokaryotic ribosomes containing about 3200 nucleotides. 23S rRNA is involved in the initiation of polypeptide synthesis.Pseudomonas mendocina: A species of gram-negative bacteria in the genus PSEUDOMONAS, which is found in SOIL and WATER.Halogens: A family of nonmetallic, generally electronegative, elements that form group 17 (formerly group VIIa) of the periodic table.ToluidinesDNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.Adrenochrome: Pigment obtained by the oxidation of epinephrine.DimethylaminesGentisates: Salts and esters of gentisic acid.Acetylation: Formation of an acetyl derivative. (Stedman, 25th ed)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.BenzophenonesHeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Glycine N-Methyltransferase: An enzyme that catalyzes the METHYLATION of GLYCINE using S-ADENOSYLMETHIONINE to form SARCOSINE with the concomitant production of S-ADENOSYLHOMOCYSTEINE.Ribosome Subunits, Small, Bacterial: The small subunit of eubacterial RIBOSOMES. It is composed of the 16S RIBOSOMAL RNA and about 23 different RIBOSOMAL PROTEINS.Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.Carmustine: A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)Euchromatin: Chromosome regions that are loosely packaged and more accessible to RNA polymerases than HETEROCHROMATIN. These regions also stain differentially in CHROMOSOME BANDING preparations.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Normetanephrine: A methylated metabolite of norepinephrine that is excreted in the urine and found in certain tissues. It is a marker for tumors.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Molecular Weight: The sum of the weight of all the atoms in a molecule.Ralstonia: A genus in the family BURKHOLDERIACEAE, comprised of many species. They are associated with a variety of infections including MENINGITIS; PERITONITIS; and URINARY TRACT INFECTIONS.5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase: An enzyme that catalyzes the formation of methionine by transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine. It requires a cobamide coenzyme. The enzyme can act on mono- or triglutamate derivatives. EC 2.1.1.13.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Biocatalysis: The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.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.Arginine: An essential amino acid that is physiologically active in the L-form.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)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)Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.RNA Cap Analogs: Analogs of RNA cap compounds which do not have a positive charge. These compounds inhibit the initiation of translation of both capped and uncapped messenger RNA.Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.Oxidoreductases, O-Demethylating: Drug metabolizing enzymes which oxidize methyl ethers. Usually found in liver microsomes.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Gram-Negative Aerobic Rods and Cocci: A group of gram-negative bacteria consisting of rod- and coccus-shaped cells. They are both aerobic (able to grow under an air atmosphere) and microaerophilic (grow better in low concentrations of oxygen) under nitrogen-fixing conditions but, when supplied with a source of fixed nitrogen, they grow as aerobes.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Parabens: Methyl, propyl, butyl, and ethyl esters of p-hydroxybenzoic acid. They have been approved by the FDA as antimicrobial agents for foods and pharmaceuticals. (From Hawley's Condensed Chemical Dictionary, 11th ed, p872)Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Hydroxamic Acids: A class of weak acids with the general formula R-CONHOH.Sulfites: Inorganic salts of sulfurous acid.Oxygen Consumption: The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)Histone Deacetylases: Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Acinetobacter calcoaceticus: A species of gram-negative, aerobic bacteria found in soil and water. Although considered to be normally nonpathogenic, this bacterium is a causative agent of nosocomial infections, particularly in debilitated individuals.

In vivo effects of new inhibitors of catechol-O-methyl transferase. (1/735)

1. The effects of two new synthetic compounds showing in vitro catechol-O-methyl transferase (COMT) inhibitor properties were studied in vivo and compared with the effects of nitecapone and Ro-41-0960. 2. QO IA (3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione), QO IIR ([2-(3,4-dihydroxy-2-nitrophenyl)vinyl]phenyl ketone), nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) were given to reserpinized rats 1 h before the administration of L-DOPA/carbidopa (LD/CD, 50:50 mg kg(-1), i.p.). Locomotor activity was assessed 1 h later. All the COMT inhibitors (COMTI), with the exception of QO IA, markedly potentiated LD/CD reversal of reserpine-induced akinesia. Similar results were obtained when the COMTI were coadministered with LD/CD. The effect of compound QO IIR was dose-dependent (7.5-30 mg kg(-1), i.p.). 3. The COMTI (30 mg kg(-1), i.p.) potentiated LD/CD reversal of both catalepsy and hypothermia of reserpinized mice. 4. QO IIR, nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) reduced striatal 3-methyl-DOPA (3-OMD) levels and increased dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels. Compound QO IA was devoid of any effect on striatal amine levels. In contrast to the other inhibitors, Ro-41-0961 reduced HVA levels as well. The effect of QO IIR on striatal amine levels was dose-dependent (7.5-60 mg kg(-1), i.p.) 5. These results suggest that the new compound QO IIR is an effective peripherally acting COMT inhibitor in vivo.  (+info)

Dehydrodicaffeic acid dilactone, an inhibitor of catechol-O-methyl transferase. (2/735)

In the screening of catechol-O-methyltransferase inhibitors, three compounds were isolated from the culture filtrate of a mushroom, Inonotus sp. One was 3,4-dihydroxycinnamic acid (caffeic acid) which had been reported as an inhibitor of this enzyme. The others were the dextrorotatory 2,6-bis-(3',4'-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]-octane 4,8-dione (dehydrodicaffeic acid dilactone) andits antipode. These new compounds inhibited both dopamine beta-hydroxylase and dopa decarboxylase and showed hypotensive activity in the SH rat.  (+info)

Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. (3/735)

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. Regulation of human COMT gene expression may be important in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression, and hypertension. The gender difference in human COMT activity and variations in rat COMT activity during the estrous cycle led us to explore whether estrogen can regulate human COMT gene transcription. Our Northern analyses showed that physiological concentrations of 17-beta-estradiol (10(-9)-10(-7) M) could decrease human 1. 3-kilobase COMT mRNA levels in MCF-7 cells in a time- and dose-dependent manner through an estrogen receptor-dependent mechanism. Two DNA fragments immediately 5' to the published human COMT gene proximal and distal promoters were cloned. Sequence analyses revealed several half-palindromic estrogen response elements and CCAAT/enhancer binding protein sites. By cotransfecting COMT promoter-chloramphenicol acetyltransferase reporter genes with human estrogen receptor cDNA and pSV-beta-galactosidase plasmids into COS-7 cells, we showed that 17-beta-estradiol could down-regulate chloramphenicol acetyltransferase activities, and COMT promoter activities dose-dependently. Functional deletion analyses of COMT promoters also showed that this estrogenic effect was mediated by a 280 base pair fragment with two putative half-palindromic estrogen response elements in the proximal promoter and a 323-base pair fragment with two putative CCAAT/enhancer binding protein sites in the distal promoter. Our findings provide the first evidence and molecular mechanism for estrogen to inhibit COMT gene transcription, which may shed new insight into the role of estrogen in the pathophysiology of different human disorders.  (+info)

Interactions of (-)-ilimaquinone with methylation enzymes: implications for vesicular-mediated secretion. (4/735)

BACKGROUND: The marine sponge metabolite (-)-ilimaquinone has antimicrobial, anti-HIV, anti-inflammatory and antimitotic activities, inhibits the cytotoxicity of ricin and diptheria toxin, and selectively fragments the Golgi apparatus. The range of activities demonstrated by this natural product provides a unique opportunity for studying these cellular processes. RESULTS: Affinity chromatography experiments show that (-)-ilimaquinone interacts with enzymes of the activated methyl cycle: S-adenosylmethionine synthetase, S-adenosylhomocysteinase and methyl transferases. Known inhibitors of these enzymes were found to block vesicle-mediated secretion in a manner similar to (-)-ilimaquinone. Moreover, the antisecretory effects of (-)-ilimaquinone and inhibitors of methylation chemistry, but not brefeldin A, could be reversed in the presence of the cellular methylating agent S-adenosylmethionine. Of the enzymes examined in the activated methyl cycle, S-adenosylhomocysteinase was specifically inhibited by (-)-ilimaquinone. Consistent with these observations, (-)-ilimaquinone was shown to obstruct new methylation events in adrenocorticotrophic hormone (ACTH)-secreting pituitary cells. CONCLUSIONS: (-)-ilimaquinone inhibits cellular methylations through its interactions with S-adenosylhomocysteinase. Furthermore, these studies indicate that the inhibition of secretion by ilimaquinone is the result of the natural product's antimethylation activity. It is likely that the ability to fragment the Golgi apparatus, as well as other activities, are also related to ilimaquinone's influence on methylation chemistry.  (+info)

COMT inhibition with tolcapone does not affect carbidopa pharmacokinetics in parkinsonian patients in levodopa/carbidopa (Sinemet). (5/735)

AIMS: Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of carbidopa. METHODS: This was an open-label study in 12 parkinsonian patients receiving optimal levodopa/carbidopa therapy and tolcapone 200 mg three times daily for 6 weeks. Blood samples were taken at baseline (i.e. before the first tolcapone intake) and after 1-2 weeks and 6 weeks so that carbidopa pharmacokinetics before and during tolcapone treatment could be assessed. RESULTS: No changes in any pharmacokinetic parameters of carbidopa were observed. The mean AUC(0,tau) and Cmax values at baseline were 0.39 microg ml-1 h and 0. 14 microg ml-1, respectively. During tolcapone treatment these values were on average 0.35 microg ml-1 h (AUC(0,tau), week 1-2), 0. 34 microg ml-1 h (AUC(0,tau), week 6 and 0.13 microg ml-1 (Cmax, weeks 1-2 and 6). tmax remained unchanged (approx. 2 h). CONCLUSIONS: These results indicate that tolcapone does not affect carbidopa elimination and that no interaction of any clinical relevance occurs between tolcapone and carbidopa.  (+info)

Catechol-O-methyltransferase activity in CHO cells expressing norepinephrine transporter. (6/735)

1. We examined the existence of catecholamine metabolizing enzymes (catechol-O-methyltransferase, COMT, and monoamine oxidase, MAO) in CHO cells transfected with norepinephrine (NE) transporter (NET) cDNA. 2. NET activity was studied by incubating cells with [3H]-NE (0. 5 microCi ml-1, 20 min) in a Na+ containing medium. Incubation with [3H]-NE lead to [3H] accumulation at 47797+/-4864 d.p.m. per well. Specific inhibitors of NET abolished this uptake. 3. During post-uptake incubation, [3H] leaked rapidly from cells and the extracellular phase comprised 89% of total radioactivity within 40 min. Both [3H] retention and [3H] 'leakage' were largely unaffected by inhibitors for MAO. In contrast, COMT inhibitors, U-0521 and Ro 41-0960, dose-dependently increased intracellular [3H]-NE retention with a maximal increase of 4.5 fold. The EC50 for Ro 41-0960 was 139-times lower than that of U-0521. U-0521 largely inhibited [3H] 'leakage' and doubled the apparent Vmax for [3H]-NE uptake. 4. Addition of U-0521 during uptake incubation increased intracellular NE content by 8 fold. Normetanephrine, the COMT-dependent metabolite of NE, was formed in large quantities during post-uptake incubation. U-0521 significantly inhibited the formation of NMN with an equal preservation of intracellular NE. 5. CHO cells expressing NET possess COMT activity, which is responsible for the metabolism of NE to form lipophilic metabolite normetanephrine. The apparent 'properties' of the NET function expressed in CHO cells changed, after inhibition of COMT, in such a way closer to that described in the native neuronal preparations.  (+info)

Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. (7/735)

Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). To examine this hypothesis, we conducted a multigenic case-control study to determine whether polymorphisms of the genes responsible for CE formation via estrogen biosynthesis (CYP17) and hydroxylation (CYP1A1) and CE inactivation (COMT) are associated with an elevated risk for breast cancer in Taiwanese women, and whether the association between genotype and risk may be modified by estrogen exposure. One hundred and fifty breast cancer patients and 150 healthy controls were recruited. PCR-based RFLP assays were used to determine the genotypes of estrogen-metabolizing genes. The breast cancer risk associated with individual susceptibility genotypes varied among the three genes and was highest for COMT, followed by CYP1A1 and CYP17. After simultaneous consideration of all three genes and other well-established risk factors of breast cancer, the COMT genotype remained the most significant determinant for breast cancer development and was associated with a 4-fold increase in risk (95% confidence interval, 1.12-19.08). Furthermore, a trend of increasing risk for developing breast cancer was found in women harboring higher numbers of high-risk genotypes (P = 0.006), including the high activity CYP17 (CYP17 A2/A2), high inducibility CYP1A1 (CYP1A1 MspI vt/vt), and low activity COMT (COMT L/L) genotypes. The association of risk with the number of susceptibility genotypes was stronger in women with prolonged estrogen exposure (indicated by a higher number of estrogen exposure years or a higher number of estrogen exposure years between menarche and first full-term pregnancy), women with higher estrogen levels (implied by early menarche), and women with a higher body mass index (> or = 22.5). On the basis of comprehensive profiles of estrogen metabolism, this study supports the possibility that breast cancer can be initiated by estrogen exposure.  (+info)

Increased mitochondrial superoxide production in rat liver mitochondria, rat hepatocytes, and HepG2 cells following ethinyl estradiol treatment. (8/735)

Ethinyl estradiol (EE) is a strong promoter of hepatocarcinogenesis. Treatment of rats with EE and other hepatic promoters induces a mitosuppressed state characterized by decreased hepatocyte turnover and reduced growth responsiveness. Previously, we identified several nuclear and mitochondrial genome-encoded mitochondrial genes whose transcripts were increased during EE-induced hepatic mitosuppression in rats and in EE-treated HepG2 cells (Chen et al. Carcinogenesis, 17, 2783-2786, 1996 and Carcinogenesis, 19, 101-107, 1998). In both cultured rat hepatocytes and HepG2 cells, EE increased respiratory chain activity (reflected by increased mitochondrial superoxide production detected as increased lucigenin-derived chemiluminescence (LDCL). In this paper, we provide additional characterizations of these effects. Increased LDCL was detected in mitochondria isolated from EE-treated rats, documenting that these estrogen effects on mitochondrial function are not confined to cells in culture. EE and estradiol (E2) increased LDCL in cultured rat hepatocytes and HepG2 cells in a dose- (beginning at 0.25 microM levels) and time-dependent response. Inhibition of P450-mediated estrogen metabolism inhibited, while direct exposure to E2 catechol metabolites enhanced LDCL. Co-treatment with glutathione ester or with the specific antiestrogen, ICI 182708 inhibited LDCL. In contrast, estrogen-induced LDCL was enhanced by glutathione depletion, and by inhibition of catechol-o-methyltransferase. These results support a working hypothesis that in liver cells, increased respiratory chain activity induced by estrogen treatment requires both metabolism to catechols and an estrogen receptor-mediated signal transduction pathway.  (+info)

TY - JOUR. T1 - L-DOPA biotransformation. T2 - Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients. AU - Dousa, M. K.. AU - Weinshilboum, Richard M. AU - Muenter, M. D.. AU - Offord, K. P.. AU - Decker, P. A.. AU - Tyce, G. M.. PY - 2003/8/1. Y1 - 2003/8/1. N2 - The objectives of this study were to determine (1) the effects of dose and drug absorption on pathways of biotransformation of L-DOPA in Parkinsonian patients treated with Sinemet, and (2) the extent to which genetically-determined variations in the activities of erythrocyte catechol O-methyltransferase and/or platelet phenol sulfotransferase might be reflected in individual differences in L-DOPA metabolism. In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites. Levels of activity for erythrocyte COMT were also reflected in individual ...
TY - JOUR. T1 - The catechol-O-methyltransferase polymorphism. T2 - Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. AU - Bilder, Robert M.. AU - Volavka, Jan. AU - Lachman, Herbert M.. AU - Grace, Anthony A.. PY - 2004/11/1. Y1 - 2004/11/1. N2 - Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val158Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D1 transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or ...
TY - JOUR. T1 - A single-nucleotide polymorphism in the fetal catechol-o-methyltransferase gene is associated with spontaneous preterm birth in African Americans. AU - Thota, Chandrasekhar. AU - Menon, Ramkumar. AU - Wentz, Melissa J.. AU - Fortunato, Stephen J.. AU - Bartlett, Jackie. AU - Drobek, Cayce O.. AU - Nair, Sangeeta. AU - Al-Hendy, Ayman. PY - 2012/2. Y1 - 2012/2. N2 - Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau). COMT converts 2- and 4-hydroxy (OH) estrogens to 2- and 4-methoxyestrogens, respectively, and can increase estrogenic milieu locally in tissues. To assess whether the increased incidence of preterm birth (PTB) among AA women is associated with single-nucleotide polymorphism (SNP) in the COMT gene, we examined variations in maternal and fetal COMT genes and their association with pregnancy outcomes (term vs preterm pregnancies) using 4 functional SNPs: rs4633, rs4680, rs4818, and rs6269 in both AA ...
BACKGROUND: Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype. METHODS: Thirty-four COMT Met(158)Met (Met-COMT) and 33 COMT Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task. RESULTS: In the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance
Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines (such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structure. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene. Two isoforms of COMT are produced: the soluble short form (S-COMT) and the membrane bound long form (MB-COMT). As the regulation of catecholamines is impaired in a number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines. COMT was first discovered by the biochemist Julius Axelrod in 1957. Catechol-O-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catecholestrogens and ...
The prefrontal cortex (PFC) dopamine system, which is critical for modulating PFC function, undergoes remodeling until at least young adulthood in primates. Catechol-o-methyltransferase (COMT) alters extracellular dopamine levels in PFC, and its gene contains a functional polymorphism (Val(158)Met) that has been associated with variation in PFC function. We examined COMT enzyme activity and protein immunoreactivity in the PFC during human postnatal development. Protein was extracted from PFC of normal individuals from 6 age groups: neonates (1-4 months), infants (5-11 months), teens (14-18 years), young adults (20-24 years), adults (31-43 years), and aged individuals (68-86 years; n = 5-8 per group). There was a significant 2-fold increase in COMT enzyme activity from neonate to adulthood, paralleled by increases in COMT protein immunoreactivity. Furthermore, COMT protein immunoreactivity was related to Val(158)Met genotype, as has been previously demonstrated. The significant increase in COMT activity
The effect of catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV) differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype x gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC) with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC) compared with Met carriers; decreased GMV in the medial ...
We investigated whether the val(158)met functional polymorphism of catechol-o-methyltransferase influenced age-related changes in grey matter density and volume, both in healthy individuals (n=80, ages 18-79) and those with Parkinsons disease (n=50). Global grey matter volumes and voxelwise estimates of grey matter volume and density were determined from structural magnetic resonance images at 3T. Male and female ValVal homozygotes (low prefrontal cortical dopamine) had more grey matter in early adulthood, but this difference disappeared with increasing age. The insula and ventral prefrontal cortex had higher grey matter volume in younger, but not older, ValVal homozygotes. Conversely, the dominant premotor cortex revealed genotypic differences in grey matter density in later life. There were no global or local interactions between Parkinsons disease and COMT val(158)met genotype on morphometry. Since the val(158)met polymorphism is associated with differences in cortical dopamine metabolism, our data
Dose-response curves of increase in pupil size and decrease in intraocular pressure with topical epinephrine have been determined in the sympathetically denervated rabbit eye. Topical pretreatment with the catechol-O-methyl transferase inhibitor U-0521 potentiated the effects of epinephrine on both the pupil and pressure. These observations suggest a possible role for catechol-O-methyl transferase in the aqueous humor dynamics of the supersensitive eye. The possible use of the denervated rabbit eye as an experimental model for the glaucomatous eye in evaluating the ocular effects of adrenergic agents is discussed.. ...
Catechol-O-methyltransferase (COMT) modulates dopamine in the prefrontal cortex (PFC) and influences PFC dopamine-dependent cognitive task performance. A human COMT polymorphism (Val(158)Met) alters enzyme activity and is associated with both the activation and functional connectivity of the PFC during task performance, particularly working memory. Here, we used functional magnetic resonance imaging and a data-driven, independent components analysis (ICA) approach to compare resting state functional connectivity within the executive control network (ECN) between young, male COMT Val(158) (n=27) and Met(158) (n=28) homozygotes. COMT genotype effects on grey matter were assessed using voxel-based morphometry. COMT genotype significantly modulated functional connectivity within the ECN, which included the head of the caudate, and anterior cingulate and frontal cortical regions. Val(158) homozygotes showed greater functional connectivity between a cluster within the left ventrolateral PFC and the rest of
Catechol O-methyltransferase (COMT) is a ubiquitous bisubstrate magnesium-dependent enzyme found in plants, animals and microorganisms. COMT catalyses the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to one of the hydroxyl oxygen atoms (preferentially the 3-hydroxyl) in a catechol substrate. Physiological substrates of COMT are catecholamine neurotransmitters such as dopamine, noradrenaline, adrenaline and their metabolites. COMT also methylates catecholic steroids such as 2-hydroxyestradiol as well as a range of other catecholic compounds including neuroactive drugs such as L-dopa, α-methyldopa and isoproterenol. COMT inhibition is a means of treating Parkinsons disease, schizophrenia and depression. There are two isoforms of human COMT: soluble cytoplasmic COMT (S-COMT), which is mainly intracellular, and a membrane-bound form (MB-COMT), which has a single-span helix contained within a 50 amino acid extension at the N-terminus.. COMT is an enzyme that plays a major role in ...
Demethylzeylasteral is among the extracts of Hook F, which has important assignments in multiple biological procedures such as irritation inhibition, aswell as immunosuppression. thus inhibits its ubiquitin-dependent degradation. Jointly, demethylzeylasteral is normally a appealing anti-tumor substance in melanoma cells. Demethylzeylasteral can be a potential inhibitor of MCL1. Melanoma can be known as malignant melanoma from melanocytes.1 Surgical resection may be the main way for sufferers NSC 105823 struggling early-stage melanoma.1, 2 Unfortunately, melanoma lesions always stay undetectable,3 which leads to the hold off for melanoma therapy.4, 5 Moreover, melanoma may break out NSC 105823 in later levels,6 when melanoma cells disseminate to varied organs, such as for example human brain, lung or liver organ.2 Consequently, surgical procedure is much less favorable for sufferers. Chemotherapeutic therapy has an important function in cases like this. Theoretically, chemotherapeutic agents ...
Objective The principal goal of the study was to check the disease-modifying aftereffect of blocking a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 using a neutralizing monoclonal antibody (mAb) starting four weeks after destabilization from the medial meniscus (DMM) in the mouse. 4-16 after medical procedures slowed cartilage degeneration and osteophyte growth but did not impact subchondral bone sclerosis. Moreover, ADAMTS-5 blockade resulted in temporary reversal of mechanical allodynia, which correlated with decreased MCP-1 production by cultured DRG cells. Conclusions This study suggests restorative effectiveness of an ADAMTS-5 mAb in the DMM model, when therapy starts early in disease. mice demonstrate long-term safety from cartilage degeneration in experimental OA induced by destabilization of the medial meniscus (DMM) [6] and in antigen-induced arthritis (AIA) [7]. Mechanical allodynia, defined as pain in response to a normally innocuous stimulus, is definitely ...
Both childhood trauma and a functional COMT genetic polymorphism have been associated with PTSD and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n=38, Met carriers, n=35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD
In the previous post, we investigated the SLC6A4 gene, which is located on the 17th human chromosome, and has a possible (but, at the current time a statistically questionable) preference towards being expressed in ADHD males than in ADHD females.. The second gene on the list, the COMT gene, is also believed to have a male-favoring genetic effect with regards to ADHD individuals. The COMT gene is located on the 22nd human chromosome. "COMT" is actually an abbreviation for catechol methyltransferase, which is an important enzyme involved in a number of neurological functions which have numerous ADHD-like implications. This important enzyme is coded for by the COMT gene (many genes share a name with the proteins which they encode). Unlike the SLC6A4 gene, this COMT gene has more grounds for statistical significance, both in gender-dependent and overall studies of genes believed to be associated with ADHD.. We have discussed the COMT gene and its role in ADHD in previous posts. We have also ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
BACKGROUND: Neuregulin1 (NRG1)-ErbB signaling has been implicated in the pathogenesis of cancer and schizophrenia. We have previously reported that NRG1-stimulated migration of B lymphoblasts is PI3K-AKT1dependent and impaired in patients with schizophrenia and significantly linked to the catechol-o-methyltransferase (COMT) Val108/158Met functional polymorphism. METHODOLOGY/PRINCIPAL FINDINGS: We have now examined AKT1 activation in NRG1-stimulated B lymphoblasts and other cell models and explored a functional relationship between COMT and AKT1. NRG1-induced AKT1 phosphorylation was significantly diminished in Val carriers compared to Met carriers in both normal subjects and in patients. Further, there was a significant epistatic interaction between a putatively functional coding SNP in AKT1 (rs1130233) and COMT Val108/158Met genotype on AKT1 phosphorylation. NRG1 induced translocation of AKT1 to the plasma membrane also was impaired in Val carriers, while PIP(3) levels were not decreased. Interestingly
Catechol-O-methyltransferase (COMT) is involved in phase II (conjugative) metabolism of catecholamines and catechol drugs, such as dopamine, as well as the catechol-estrogens. COMT transfers a donor methyl-group from S-adenosylmethionine to acceptor hydroxy groups on catechol structures (aromatic ring structures with vicinal hydroxy-groups).(1) Bioactive catecholamine metabolites are metabolized by COMT in conjunction with monoamine oxidase (MAO):. -Norepinephrine is methylated by COMT forming normetanephrine.. -Epinephrine is methylated by COMT forming metanephrine.. -Dopamine is converted to homovanillic acid through the combined action of MAO and COMT.. Parkinsonism patients receiving levodopa (L-DOPA) therapy are frequently also prescribed a COMT inhibitor to minimize metabolism of L-DOPA by COMT, thereby prolonging L-DOPA action.. COMT is also involved in the inactivation of estrogens. Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol.(2) ...
Catechol-O-methyltransferase (COMT) catabolises the catecholamine neurotransmitters and influences cognitive function. COMT modulates dopamine levels in the prefrontal cortex and its action in this region is generally invoked to explain its effects on cognition. However, its role in other brain regions important for cognitive function remains largely unexplored. Here, we investigated COMTs impact on dopamine metabolism in the hippocampus and hippocampal-dependent behaviour. We examined the acute effects of a centrally-acting COMT inhibitor, tolcapone (30 mg/kg i.p.), on dopamine metabolism in the rat dorsal hippocampus, assessed both in tissue homogenates and extracellularly, using in vivo microdialysis. Additionally, we investigated the effect of tolcapone on delayed-rewarded alternation and spatial novelty preference, behavioural tasks which are dependent on the dorsal hippocampus. Tolcapone significantly modulated dopamine metabolism in the dorsal hippocampus, as indexed by the depletion of
Catechol-O-methyltransferase (COMT) plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val(158)Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC) dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26) were subjected to an [(18)F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
5 Dopamine Agonists Dopamine agonists directly stimulate the dopamine receptors, with bromocriptine (Parlodel®) and pergolide (Permax®) having been available in Canada for the treatment of PD for many years. More recently, two newer dopamine agonists - ropinirole (Requip®) and pramipexole (Mirapex®) - have become available. These differ from the older compounds in that they are not ergot derivatives, and are therefore devoid of ergot-related side effects such as retroperitoneal or pleural fibrosis. 3 Catechol-O-Methyl Transferase (COMT) Inhibitors Levodopa is metabolized peripherally not only by decarboxylase (as described above) but also by COMT. The latter is a ubiquitous enzyme, and is sufficiently active that when levodopa is administered with a peripheral decarboxylase inhibitor, only about 10% of a given dose will reach the brain intact [15]. Entacapone (Comtan®) inhibits the peripheral metabolism of levodopa by COMT, thereby increasing its availability to the brain, and increasing ...
Introduction: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. Methods: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2822 individuals. Results: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of ,= 1 fracture was 37.2% in COMTLL, 35.7% in COMTHL and 30.4% in COMTHH (p,0.05). Early fractures (,= 50 years of age) were less common in COMTHH than in the combined COMTLL+HL genotype, ...
Teva-Entacapone: Entacapone belongs to a group of medications called catechol-O-methyl transferase (COMT) inhibitors. It is used along with levodopa-carbidopa or levodopa-benserazide to treat Parkinsons disease.
Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: any doses of a controlled-release (CR) LD apart from a single daily bedtime dose or any doses of Rytary, additional CD (eg, Lodosyn) or benserazide (eg, Serazide), or catechol-O-methyl transferase inhibitors (entacapone or tolcapone) or medications containing these inhibitors (Stalevo). Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: nonselective monoamine oxidase (MAO) inhibitors, apomorphine, or dopaminergic blocking agents including antiemetics ...
1292] Mattay, V. S., Goldberg T. E., Fera F., Hariri A. R., Tessitore A., Egan M. F., et al. (2003). Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proceedings of the National Academy of Sciences of the United States of America. 100(10), 6186 - 6191. ...
Quercetin and fisetin, known as catechol-containing flavonoids, could positively affect the absorption of catechins due to their strong affinity for catechol-O-methyl transferase (COMT), which can methylate and cause the excretion of catechins. The current study examined the effect of quercetin and fisetin o
Using an isolated canine heart preparation, the myocardial norepinephrine pool was labeled by injecting tritiated norepinephrine into the blood perfusing the heart. The extraction of the norepinephrine during a single circulation through the coronary bed was shown to be large (74%). As the isotopic material, which was extracted, was released spontaneously from the norepinephrine pool 75% to 88% of it was metabolized before appearing in the coronary venous blood. The chief metabolite has been demonstrated to be normetanephrine which accounts for 39.0% to 61.7% of the spontaneously released norepinephrine. Because of this it is concluded that catechol-O-methyl transferase is the enzyme primarily responsible for the metabolic inactivation of norepinephrine in the canine heart. When release was increased by the injection of tyramine, more of the released norepinephrine appeared unmetabolized in coronary venous blood, suggesting that the enzymatic process by which norepinephrine is inactivated may be ...
Nedić, Gordana and Matea Nikolac, Matea and Borovečki, Fran and Hajnšek, Sanja and Muck-Šeler, Dorotea and Pivac, Nela (2010) Association study of a functional catechol-o-methyltransferase polymorphism and smoking in healthy Caucasian subjects. Neuroscience Letters, [Epub . ISSN 0304-3940 ...
The stress of foot shock in rats induces large decreases in the level of brain norepinephrine but does not greatly alter the concentration of serotonin or dopamine in brain. These decrements in norepinephrine are not limited to any region and occur uniformly throughout the brain. However, absolute levels of these amines are not a true indicator of their dynamic state. By various techniques it could be demonstrated that the stress of foot shock accelerates the metabolism of dopamine and serotonin to the same degree as norepinephrine; the only difference being that dopamine and serotonin are rapidly resynthesized, whereas norepinephrine in the brain cannot be regenerated at the same rate. Furthermore, the increased catabolism of brain norepinephrine with stress is blocked by monoamine oxidase inhibitors, whereas catechol-O-methyltransferase inhibitors do not impede accelerated degradation.. ...
Parkinsons disease is a progressive degenerative disorder of the central nervous system. The hallmark physical signs are tremor, rigidity and bradykinesia. Idiopathic Parkinsons disease is caused by the progressive loss of dopaminergic neurons in the substantia nigra and nigrostriatal pathway of the midbrain. Secondary parkinsonism may be caused by certain drugs (e.g., metoclopramide and haloperidol) or by cerebrovascular disease (e.g., multiple lacunar strokes). The disease can usually be diagnosed based on the history and physical findings. Dopamine replacement is still considered the most efficacious treatment for Parkinsons disease, but dopamine agonists, formerly prescribed only as adjunctive therapy, are emerging as useful initial therapy. Other pharmacologic treatments include drugs that inhibit dopamine-metabolizing enzymes (monoamine oxidase-B and catechol O-methyltransferase). Injections of botulinum toxin can be helpful in patients with associated dystonia or blepharospasm. Surgery may be
PRF readers can get free access to a selected Journal of Pain paper each month, thanks to the American Pain Society. Get the free full text of the selection from the December 2017 issue here.. ...
Psychopharmacological modulation of the catecholaminergic system can enhance some aspects of cognitive function. For example, COMT inhibitors can slightly improve working memory/executive function. Similarly, modafinil, a catecholaminergic agonist that increases extracellular dopamine in the prefrontal cortex was also shown to improve delay-dependent working memory. Differences in the response between individuals might be related to a number of factors, including variations in the genes. The recent finding that a polymorphism in the catechol-o-methyl-transferase (COMT) gene, which produces a 4 fold change in enzyme activity, accounts for 4% of the variance in performance of working memory tasks in humans suggest that COMT genotype may predict response to COMT inhibitors or to other agonists that increase catecholaminergic function in the frontal cortex.. In the present investigation our goal is to examine, in normal controls and patients with schizophrenia, the effect of modafinil, a drug that ...
Objective: Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. Method: One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. Results: For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. Conclusions: We relate this result to available evidence indicating that met carriers perform better ...
Children reporting psychotic experiences (PEs) are at increased risk of developing psychosis in adulthood. Cognitive deficits and anxiety disorders often precede psychotic disorders and are associated with higher risk of PEs. While the high activity alleles of variants within COMT have been associated with cognitive deficits, and the low activity alleles with higher risk of anxiety disorders, no associations of COMT with PEs have been found. One possible explanation is that the association between COMT and PEs is indirect, through cognitive function and anxiety disorders. We examined whether the association between PEs and COMT (four single nucleotide polymorphisms and three haplotypes) is indirect, through cognition or anxiety disorders. 6,784 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) were genotyped and completed neurocognitive assessments at ages 8 and 11, as well as semi-structured interviews for anxiety disorders and PEs at ages 10 and 12, respectively. ...
Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia--relationship with COMT Val¹⁰⁸/¹⁵⁸Met polymorphism, gender and symptomatology. - Erik Boot, Jan Booij, Nico Abeling, Julia Meijer, Fabiana da Silva Alves, Janneke Zinkstok, Frank Baas, Don Linszen, Thérèse van Amelsvoort
Wang, Y., Gau, Y,-T.A., Le, H.N.D., Bergles, D.E., Kang, J.U. (2017). Image analysis of dynamic brain activity based on gray distance compensation. Appl Sci, 7(8), 858.. Li, A., Liang, W., Guan, H., Gau, Y.-T.A., Bergles, D.E., and Li, X. (2017). Focus scanning with feedback-control for fiber-optic nonlinear endomicroscopy. Biomed Opt Express, 8(5), 2519-27.. Le, H.N.D., Gau, Y.-T.A., Rahmim, A., Wong, D.F., Kang, J.U., and Bergles, D.E. (2016). Through-skull vasculature assessment using fluorescence brain imaging on murine models at around 800 nm. Proc. SPIE 10051, Neural Imaging and Sensing, 10051-21.. Tsai, S.-J., Gau, Y.-T.A., Hong, C.-J., Liou, Y.-J., Yu, Y.W.-Y., Chen, T.-J., and Weissman, M.M. (2009). Sexually dimorphic effect of catechol-O-methyltransferase val158met polymorphism on clinical response to fluoxetine in major depressive patients. J. Affect. Disord. 113, 183-187.. Gau, Y.-T.A., Hong, C., and Tsai, S. (2008). Can antidepressants act as potential pro-neoplastic agents in ...
Section of Occupational and Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns ...
2008, Dilsat Ozkan Ariksoysal , Burcin Tezcanli , Buket Kosova,Mehmet Ozsoz ,Design of electrochemical biosensor systems for the detection of specific DNA sequences in PCR-amplified nucleic acids related to the catechol-O-methyltransferase val1 08/158Met polym val1 08/158Met polymorphism based on intrinsic guanine signal ,Anal.Chem. 80 , 3 : 588- ...
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Bachmann S (2014) Umgang mit chronischen körperlichen Erkrankungen. Praxis, 103: 379-384. Bachmann S, Degen C, Geider FJ, Schröder J (2014) Neurological soft signs in the clinical course of schizophrenia: results of a meta-analysis. Front Psychiatry, 5: 185. Baldinger P, Hahn A, Mitterhauser M, Kranz GS, Friedl M, Wadsak W, Kraus C, Ungersböck J, Hartmann A, Giegling I, Rujescu D, Kasper S, Lanzenberger R (2014) Impact of COMT genotype on serotonin-1A receptor binding investigated with PET. BRAIN STRUCT FUNCT, 219: 2017-28. Boraska V, Franklin CS, Floyd JAB, Thornton LM, Huckins LM, Southam L, Rayner NW, Tachmazidou I, Klump KL, Treasure J, Lewis CM, Schmidt U, Tozzi F, Kiezebrink K, Hebebrand J, Gorwood P, Adan RAH, Kas MJH, Favaro A, Santonastaso P, Fernández-Aranda F, Gratacos M, Rybakowski F, Dmitrzak-Weglarz M, Kaprio J, Keski-Rahkonen A, Raevuori A, Van Furth EF, Slof-Op t Landt MCT, Hudson JI, Reichborn-Kjennerud T, Knudsen GPS, Monteleone P, Kaplan AS, Karwautz A, Hakonarson H, ...
The inhibition of soluble catechol-O-methyltransferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after singl
The present invention relates to 4-pyridinone compound as catechol -O- methyltransferase (COMT) inhibitors and are useful in the treatment or prevention of COMT enzyme is involved in neurological and psychiatric disorders and diseases. The present invention also relates to the use of these compounds comprises pharmaceutical compositions of these compounds and compositions in the prevention or disease involving COMT treatment.
1) It looks like the SNP in question does show some variation world wide. Europeans seem to have a higher frequency of the MET/MET genotype than Africans, while Asians tend to be lowest ...
PURPOSE: The association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated. PATIENTS AND METHODS: The study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers. RESULTS: The VV (high activity) genotype of the V432L polymorphism from CYP1B1 (odds ratio [OR] = 1.36; 95% CI, 1.03 to 1.79; P = .031), and the long allele (| 175 bp) of the TTTA repeat from CYP19 (OR, 1.26; 95% CI, 1.08 to 1.47; P = .003) were significantly associated with the risk of prostate cancer. An additive effect was observed when we combined the two at-risk alleles (OR = 1.63; 95% CI, 1.24 to 2.13; P | .001). The association was stronger for the CYP1B1 VV genotype (OR = 1.55; 95
A possible exception to the single-genes-dont-change-behavior-in-isolation rule might be the COMT gene. This gene makes the enzyme that breaks down several neurotransmitters in the brain, including dopamine. Like many genes, individuals may have different variations (or alleles) of the gene. However, unlike alleles that change an individuals hair color, different alleles in the COMT gene have been associated with striking differences in cognitive function. Incredibly, these differences arise due to a single amino acid difference in the enzyme! Substituting valine for methionine at position 158 in the gene is associated with a host of poorer psychological outcomes. As each person inherits one copy of the gene from each of his parents, individuals can either have two valines, two methionines, or one of each. Interestingly enough, the number of valines correlates with the degree of negative outcome. For example, a 2008 study was conducted in which people recorded the events that were taking place ...
We investigated factors affecting sensitivity and reproducibility of radioenzymic (catechol-O-methyltransferase) measurement of plasma catecholamines. There was no apparent deterioration of catecholamine during storage at -20 degrees C for 240 days. Accuracy and sensitivity of the assay depended mostly on the method of transferase preparation; its preparation by adjusting the pH to 6.8 before fractionation with ammonium sulfate resulted in an unsuitable enzyme with a relatively high background-radioactivity count, particularly for neorepinephrine and dopamine.
Shop L-olivosyl-oleandolide 3-O-methyltransferase ELISA Kit, Recombinant Protein and L-olivosyl-oleandolide 3-O-methyltransferase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Rabbit polyclonal antibody raised against synthetic peptide of COMT. A synthetic peptide corresponding to 15 amino acid at internal region of human COMT. (PAB27824) - Products - Abnova
Hi all, Ive just received my 23andme results and ran it through Genetic Genie. Can anyone help me out? TIA! Renee COMT V158M -/- COMT H62H -/-...
Background Following voxel-based morphometry (VBM), brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been shown to affect human brain morphology in Caucasians. However, little is known about the specific role of the Met/Met genotype on brain structure. Moreover, the relationship between BDNF Val66Met polymorphism and Chinese brain morphology has not been studied. Methodology/Principal Findings The present study investigated brain structural differences among three genotypes of BDNF (rs6265) for the first time in healthy young Chinese adults via cortical thickness analysis and VBM. Brain differences in Met carriers using another grouping method (combining Val/Met and Met/Met genotypes into a group of Met carriers as in most previous studies) were also investigated using VBM. Dual-approach analysis revealed less gray matter (GM) in the frontal, temporal, cingulate and insular cortices in the Met/Met group compared with the Val/Val group (corrected, P|0.05). Areas with less GM
The present study confirms and extends previous findings28 29 that tolcapone enhances the efficacy of levodopa. Whereas initial studies were focused on single dose6 or short term (one to six weeks) multiple dose22 26 coadministration of tolcapone with levodopa/decarboxylase inhibitor, the present study showed that multiple dose (tid) treatment with tolcapone results in reduced severity of "wearing off" type motor fluctuations in levodopa treated patients for three months and that this response is maintained over time.. Treatment with tolcapone significantly decreased mean "off" time (by ,20%) and increased mean "on" time (by ,25%), compared with placebo. Analysis of primary end point "on/off" data disclosed that both tolcapone dosages were equally effective in increasing "on" time, but the 100 mg tid dosage was more effective in decreasing "off" time. However, the mean reduction in levodopa dosage by month 3 was greater with 200 mg tolcapone tid than with 100 mg tid This reduction was maintained ...
Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning, where homozygosity for the Met allele (linked to heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across three separate samples that were combined for analyses (age: 21.80 ± 3.95; n = 392; 268 female; ...
Catechol-O-methyltransferase (COMT) modulates dopamine levels in the prefrontal cortex. The human gene contains a polymorphism (Val158Met) that alters enzyme activity and influences PFC function. It has also been linked with cognition and anxiety, but the findings are mixed. We therefore developed a novel mouse model of altered COMT activity. The human Met allele was introduced into the native mouse COMT gene to produce COMT-Met mice, which were compared with their wild-type littermates. The model proved highly specific: COMT-Met mice had reductions in COMT abundance and activity, compared with wild-type mice, explicitly in the absence of off-target changes in the expression of other genes. Despite robust alterations in dopamine metabolism, we found only subtle changes on certain cognitive tasks under baseline conditions (eg, increased spatial novelty preference in COMT-Met mice vs wild-type mice). However, genotype differences emerged after administration of the COMT inhibitor tolcapone: performance of
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Jie Tang1 ,Yanjun Li1 ,Jiayuan Xu1 ,Wen Qin1 ,Qian Su2 ,Qiang Xu1 ,Bing Liu3 ,Tianzi Jiang3 ,Chunshui Yu1 1 Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, Peoples Republic of China. 2 School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, Peoples Republic of China. 3 Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, Peoples Republic of China. Abstract. Catechol-O-methyltransferase (COMT) affects brain connectivity via modulating the dopamine system, with an expected greater effect of haplotypes than single-nucleotide polymorphism (SNP). The action pathway from COMT to dopamine to connectivity is theoretically dependent on the gene expression of dopamine receptors. Here, we aimed to investigate the impact of COMT haplotypes on brain functional connectivity density (FCD) in ...
Normetanephrine is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is excreted in the urine and found in certain tissues. It is a marker for catecholamine-secreting tumors such as pheochromocytoma. ...
Abstract: The COMT gene is thought to contribute to the cognitive/psychiatric phenotypes in 22q11.2 deletion syndrome. We measured these manifestations against the Val/Met alleles of the COMT gene, in 40 nonpsychotic 22q11DS children. The Val allele was associated with poor IQ, processing speed, executive function and a higher frequency of anxiety disorders, underscoring the importance of the COMT gene in the childhood psychopathology in 22q11DS.. COMT and anxiety and cognition in children with chromosome 22q11.2 deletion syndrome ...
Markett, S., Montag, C., Heeren, B., Saryiska, R., Lachmann, B., Weber, B., & Reuter, M. (2016). Voxelwise eigenvector centrality mapping of the human functional connectome reveals an influence of the catechol-O-methyltransferase val158met polymorphism on the default mode and somatomotor network. Brain Structure and Function, 221(5), 2755-2765 ...
BACKGROUND: Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness. METHOD: Healthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. RESULTS: Response bias, the participants propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the ...
She suggested, but did not say, that chronic fatigue syndrome could be triggered as early as pregnancy and then not show up for 20 or 40 or 50 years until another window of vulnerability opens up - perhaps during a stressful period, another infection, toxic overexposure. (She noted that the stress response is similar in all these cases). Indeed, that model of disease, she said, could apply to outbreaks of autism and ADHD in early life, multiple sclerosis, schizophrenia and ME/CFS in middle life and Parkinsons and Alzheimers disease in later life.. Cannabis triggered schizophrenia during adolescence is an example of the three factors combining in a perfect storm to cause a devastating disease. It turns out that bringing together one form of a COMT gene (the COMT gene, oddly enough is implicated in ME/CFS), the tumultuous physiological time of adolescence, and an environmental factor (cannabis) you get an increased risk of (gulp) schizophrenia. Basically smoking pot when youre an adolescent ...
epigallocatechin (EGC) are the major polyphenolic constituents in green tea. Inthis study, we characterized the enzymology of cytosolic catechol-O-methyltransferase(COMT)-catalyzed methylation of EGCG and EGC in humans, mice,and rats. At 1 µM, EGCG was readily methylated by liver cytosolicCOMT to 4-O-methyl-EGCG and then to 4,4-di-O-methyl-EGCG; EGCwas methylated to 4-O-methyl-EGC. The Km and Vmax values forEGC methylation were higher than EGCG; for example, with humanliver cytosol, the Km were 4.0 versus 0.16 µM and Vmax were 1.28 versus 0.16 nmol/mg/min. Rat liver cytosol had higher COMT activitythan that of humans or mice. The small intestine had lower specificactivity than the liver in the methylation of EGCG and EGC. Glucuronidationon the B-ring or the D-ring of EGCG greatly inhibited the methylationon the same ring, but glucuronidation on the A-ring of EGCG orEGC did not affect their methylation. Using EGC and 3,4-dihydroxy-L-phenylalanineas substrates, EGCG, 4-O-methyl-EGCG, and ...
Adeline Galvanin, Lilia Ayadi, Mark Helm, Yuri Motorin, Virginie Marchand. Mapping and Quantification of tRNA 2′-O-Methylation by RiboMethSeq. Methods Mol Biol, pp.273-295, 2019, ⟨10.1007/978-1-4939-8808-2_21⟩. ⟨hal-01957102⟩ ...
MetabolismBiosynthesis of cofactors, prosthetic groups, and carriersMenaquinone and ubiquinone3-demethylubiquinone-9 3-O-methyltransferase (TIGR01983; EC 2.1.1.64; HMM-score: 13.1) ...
Background The interaction of the association of dopamine genes, impulsivity and childhood trauma with substance abuse remains unclear. Objectives To clarify the impacts and the interactions of the Catechol -O-methyltransferase (COMT) gene, impulsivity and childhood trauma on the age of onset of heroin use among heroin dependent patients in China. Methods 202 male and 248 female inpatients who meet DSM-IV criteria of heroin dependence were enrolled. Impulsivity and childhood trauma were measured using BIS-11 (Barratt Impulsiveness Scale-11) and ETISR-SF (Early Trauma Inventory Self Report-Short Form). The single nucleotide polymorphism (SNP) rs737866 on the COMT gene-which has previously been associated with heroin abuse, was genotyped using a DNA sequence detection system. Structural equations model was used to assess the interaction paths between these factors and the age of onset of heroin use. Principal Findings Chi-square test indicated the individuals with TT allele have earlier age of onset
Title:Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major Depressive Disorder (MDD). VOLUME: 11 ISSUE: 3. Author(s):Neslihan Aygun Kocabas. Affiliation:Universite Libre de Bruxelles, Laboratoire de Neurologie Experimentale, Campus Hopital Erasme C2.124, 808 Route de Lennik, 1070 Bruxelles, Belgium.. Keywords:COMT gene, pharmacogenetics, antidepressant, treatment response, snp, Catechol O Methyl Transferase, Major Depressive disorder , COMT, MDD, rs4680, Antidepressant treatment, Dopamine. Abstract:Psychiatry is a specialty where the application of pharmacogenomics approaches is made to the study of interindividual differences in response to antidepressants. It is highly applied for improving patient treatment. Major depressive disorder (MDD) is a common and complex disorder resulting from genetic and environmental interactions. Less than 40% of patients with MDD achieve remission, and even after several treatment trials, one in three patients do not ...
TY - JOUR. T1 - A chemical model of catechol-O-methyltransferase. Methylation of 3,4-dihydroxybenzaldehyde in aqueous solution. AU - Sugata, S.. AU - Ishihara, S.. AU - Watanabe, Y.. AU - Itoh, Yoshiko. AU - Matsushima, Y.. PY - 1989. Y1 - 1989. UR - http://www.scopus.com/inward/record.url?scp=0024362087&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0024362087&partnerID=8YFLogxK. M3 - Article. C2 - 2630085. AN - SCOPUS:0024362087. VL - 37. SP - 1143. EP - 1146. JO - Chemical and Pharmaceutical Bulletin. JF - Chemical and Pharmaceutical Bulletin. SN - 0009-2363. IS - 5. ER - ...
Dr. Sarah Forester. According to the American Cancer Society, colon cancer is the third most common type of cancer in the United States for both men and women. Consumption of a healthy diet, including fruits and vegetables, may help prevent this disease. Anthocyanins are a class of phenolic compounds that contribute to the color of foods such as strawberries, pomegranates, and grapes. These compounds have been shown to reduce the incidence of colon cancer, yet they are heavily metabolized in the body, limiting their anti-cancer activities. Specifically, anthocyanins are methylated by catechol-O-methyltransferase (COMT), transforming them into less bioactive compounds. COMT activity can be inhibited by a drug called entacapone. This drug is used to improve the symptoms of Parkinsons disease patients, yet it could also be used to improve the anti-cancer effects of food-derived anthocyanins. The purpose of this project is to test if entacapone can enhance intracellular levels and anti-cancer ...
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Tolcapone; Tolcapone may be used in COMT-mediated cell signaling studies. Tolcapone has been used in methyltransferase assay in human embryonic kidney 293 cells.
Egan M. F., Goldberg T. E., Kolachana B. S., Callicott J. H., Mazzanti C. M., Straub R.E., Goldman, D. and Weinberger, D. R. (2001). Effect of COMT Val 108/158 Met Genotype on Frontal Lobe Function and Risk for Schizophrenia Proceedings of the National Academy of Science 98(12): 6917-6922CrossRefGoogle Scholar ...
The influence of genetic factors on error processing and response monitoring functions has frequently been studied in the past (Klein et al., 2007; Krämer et al., 2007; Beste et al., 2010a). Until now, no study examined the role of neurotrophins for these important cognitive functions. Furthermore, a fine-meshed analysis in terms of differences in neural synchronization processes that are important for information processing (Varela et al., 2001) and that may underlie observed genotype-dependent differences has not been carried out. To fill this gap, we examined modulatory influences of the functional BDNF Val66Met polymorphism (rs6265) on the neuronal dynamics underlying error processing, with special emphasizes on neural synchronization processes.. We show that the Val/Val genotype has an increased Ne/ERN, compared with the combined Val/Met-Met/Met genotype group. This pattern is mirrored by the behavioral data showing stronger posterror slowing effects in the Val/Val compared with the ...
Given that both clinical and preclinical studies suggest that BDNF may be involved in the therapeutic action of antidepressants, BDNF appears to be a good candidate gene for the pharmacogenetic study of antidepressants. In our 2003 study on 110 MDD outpatients, we examined the association between the BDNF Val66Met polymorphism and response to 4-week antidepressant (fluoxetine) treatment.17 A trend (p=0.086) to higher total HAM-D-score percentage change was noted for the Val/Met-heterozygote patients in comparison to those bearing the homozygote (Val/Val or Met/Met). While similar findings have been reported in some of the subsequent studies of this polymorphism and the antidepressant response23,24, other studies demonstrated a better response in subjects with the Met variant25-27 or they found no association at all (Table 1).28,29 The inconsistencies in these findings might be due to the small sample sizes used in some of the studies. They could also have arisen as the result of differences in ...
TY - JOUR. T1 - Genetic polymorphisms and prediction of chronic post-surgical pain after hysterectomy-a subgroup analysis of a multicenter cohort study. AU - Hoofwijk, Daisy M. N.. AU - van Reij, Roel R. I.. AU - Rutten, Bart P. F.. AU - Kenis, Gunter. AU - Theunissen, Maurice. AU - Joosten, Elbert A.. AU - Buhre, Wolfgang F.. AU - van den Hoogen, Nynke J.. PY - 2019/9. Y1 - 2019/9. KW - chronic pain. KW - genetic. KW - hysterectomy. KW - pain. KW - polymorphisms. KW - post-operative. KW - CATECHOL-O-METHYLTRANSFERASE. KW - PERSISTENT BREAST PAIN. KW - POSTOPERATIVE PAIN. KW - RISK-FACTORS. KW - NEUROPATHIC PAIN. KW - COMT. KW - ASSOCIATION. KW - WOMEN. KW - QUESTIONNAIRE. KW - PREVALENCE. U2 - 10.1111/aas.13413. DO - 10.1111/aas.13413. M3 - Article. VL - 63. SP - 1063. EP - 1073. JO - Acta Anaesthesiologica Scandinavica. JF - Acta Anaesthesiologica Scandinavica. SN - 0001-5172. IS - 8. ER - ...
Learn about Comtan (Entacapone) may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling, reviews, and related medications.
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Entacapone, sold under the brand name Comtan among others, is a medication commonly used in combination with other medications for the treatment of Parkinsons disease. Entacapone together with levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinsons disease signs and symptoms for a greater length of time than levodopa and carbidopa therapy alone. Entacapone is a selective and reversible inhibitor of the enzyme catechol-O-methyltransferase (COMT). When taken together with levodopa (L-DOPA) and carbidopa, entacapone stops catechol-O-methyltransferase from breaking down and metabolizing levodopa, resulting in an overall increase of levodopa remaining in the brain and body. Carbidopa/levodopa/entacapone (Stalevo), a medication developed by Orion Pharma and marketed by Novartis, is a single tablet formulation that contains levodopa, carbidopa, and entacapone. Entacapone is used in addition to levodopa and carbidopa for people with Parkinsons disease to ...
Met substitution results in lower BDNF activity, possibly due to inefficient trafficking of BDNF to secretory granules and reduced activity-dependent BDNF release.. Studies showed higher frequency of Met allele in Asian women with primary dysmenorrhea (PDM) and Met/Met homozygote associated with PDM status and higher pain compared with Val carrier; higher drug consumption in medication-overuse headache. In response to experimental pain, Met carriers showed 1) higher dopamine release in nucleus accumbens during painful muscle stimulation and a blunted dopamine response to placebo; 2) lower esophageal pain thresholds to electrical stimulation; 3) reduced cortical decremental response to repeated electrical stimuli; 4) augmented cortical pain processing in response to painful electrical stimulation in people with chronic pain and reduced pain processing in pain-free controls.. Negative results: Xiao et al., 2012 (fibromyalgia); Marziniak et al., 2008 (migraine); Sutherland et al., 2014 (migraine). ...
Title:Current Understanding of the Interplay Between Catechol-OMethyltransferase Genetic Variants, Sleep, Brain Development and Cognitive Performance in Schizophrenia. VOLUME: 11 ISSUE: 3. Author(s):Valter Tucci, Glenda Lassi and Martien J. Kas. Affiliation:Department of Neuroscience and Brain technologies, Istituto Italiano di Tecnologia. Via Morego, 30, 16131, Genoa, Italy.. Keywords:COMT, sleep, cognition, brain development, Schizophrenia, Catechol O Methyl Transferase, COMT, Electroencephalographic technology, EEG, Electromyographic technology, Non-REM, slow wave sleep. Abstract:Abnormal sleep is an endophenotype of schizophrenia. Here we provide an overview of the genetic mechanisms that link specific sleep physiological processes to schizophrenia-related cognitive defects. In particular, we will review the possible relationships between catechol-O-methyltransferase (COMT), sleep regulation and schizophrenia development. Recent studies validate the hypothesis that COMT mutations may trigger ...
Patients should be instructed to take entacapone tablets only as prescribed. Patients should be informed that hallucinations can occur. Patients should be advised that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sweating. Hypotension may occur more frequently during initial therapy. Accordingly, patients should be cautioned against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods, and especially at the initiation of treatment with entacapone tablets. Patients should be advised that they should neither drive a car nor operate other complex machinery until they have gained sufficient experience on entacapone tablets to gauge whether or not it affects their mental and/or motor performance adversely. Because of the possible additive sedative effects, caution should be used when patients are taking other CNS depressants in combination with entacapone tablets. Patients should ...
181479PRTChlamydomonas reinhardtii 1Met Ala Leu Ala Ser Gly Val Gly Arg Arg Gln His Val Ser Ala Ser 1 5 10 15 Pro Ser Arg Ser Arg Gly Val Pro Ser Pro Arg Leu Ser Pro Val His 20 25 30 Ala Asn Ala Pro Ala Val Ala Glu Arg Arg Thr Glu Pro Leu Leu Lys 35 40 45 Gln Glu Leu Val Asp Tyr Leu Lys Ser Gly Cys Arg Pro Arg Ser Ala 50 55 60 Trp Arg Ile Gly Thr Glu His Glu Lys Leu Gly Phe Asn Leu Ala Asp 65 70 75 80 Asn Ser Arg Met Asn Tyr Asp Gln Ile Ala Gln Val Leu Arg Lys Leu 85 90 95 Glu Ala Arg Phe Gly Trp Glu Pro Ile Met Glu Glu Gly Arg Ile Ile 100 105 110 Gly Val Gln Leu Asp Gly Gln Ser Val Thr Leu Glu Pro Gly Gly Gln 115 120 125 Phe Glu Leu Ser Gly Ala Pro Val Glu Thr Ile His Lys Thr Cys Ala 130 135 140 Glu Val Asn Ser His Leu Tyr Gln Val Lys Ala Ile Cys Glu Glu Leu 145 150 155 160 Gln Thr Gly Phe Leu Gly Val Gly Phe Asp Pro Lys Trp Ala Ile Ser 165 170 175 Asp Val Pro Met Met Pro Lys Gly Arg Tyr Lys Leu Met Lys Ser Tyr 180 185 190 Met Pro Thr Val Gly Ser Met Gly Leu Asp Met Met Phe Arg Thr Cys 195 200 ...
If you are born with or are exposed to more estrogen in your body (both natural and man-made) then you will have a tendency to have more dopamine in your brain because your COMT/MAO pathway has been slowed. This elevation of dopamine and catecholamines makes you much more likely to experience anxiety, worry, insomnia, chronic pain and other conditions associated with a slow COMT/MAO system. A woman with too much estrogen may wake up and feel like she cannot handle another stressful thing at all. And this woman with excess estrogen will also have a slowed COMT and MAO system that will tend to make her more sensitive to stress. Based on the information I have shared with you so far, we can see how being estrogen dominant will make it more difficult to deal with stressful life situations like a new job, new child, new relationship, relocating to a new town, etc. Excess estrogen will literally slow down your methylation pathways making you less able to tolerate even the slightest increase in stress. ...
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Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α
Azole antifungals (eg, ketoconazole), catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), delavirdine, HIV protease inhibitors (eg, ritonavir), macrolide antibiotics (eg, clarithromycin), MAOIs (eg, phenelzine), nefazodone, short-acting beta-agonist bronchodilators (eg, albuterol), telithromycin, or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Seroflo Inhaler side effects. SIDE EFFECTS. All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:. Diarrhea; dizziness; headache; mild muscle or bone pain; nausea; nervousness; throat irritation; tremor; vomiting.. Seek medical attention right away if any of these SEVERE side effects occur:. Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue);. behavior changes;. blurred vision or other ...
Azole antifungals (eg, ketoconazole), catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), delavirdine, HIV protease inhibitors (eg, ritonavir), macrolide antibiotics (eg, clarithromycin), MAOIs (eg, phenelzine), nefazodone, short-acting beta-agonist bronchodilators (eg, albuterol), telithromycin, or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Seroflo Inhaler side effects. SIDE EFFECTS. All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:. Diarrhea; dizziness; headache; mild muscle or bone pain; nausea; nervousness; throat irritation; tremor; vomiting.. Seek medical attention right away if any of these SEVERE side effects occur:. Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue);. behavior changes;. blurred vision or other ...
Health, ...Philadelphia PA 25 February 2010 - The 1994 genocide in Rwanda resul...However even under stress as extreme as genocide not all individuals...The clues may come from molecular genetics. Scientists already know t...Individuals homozygous for the Met allele of this COMT polymorphism ha...,Rwandan,genocide,survivors,provide,new,insights,into,resilience,and,PTSD,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
PURPOSE: To study the PK interaction of L-dopa/benserazide in rats. METHODS: Male rats received a single oral dose of 80 mg/kg L-dopa or 20 mg/kg benserazide or 80/20 mg/kg L-dopa/benserazide. Based on plasma concentrations the kinetics of L-dopa, 3-O-methyldopa (3-OMD), benserazide, and its metabolite Ro 04-5127 were characterized by noncompartmental analysis and a compartmental model where total L-dopa clearance was the sum of the clearances mediated by amino-acid-decarboxylase (AADC), catechol-O-methyltransferase and other enzymes. In the model Ro 04-5127 inhibited competitively the L-dopa clearance by AADC. RESULTS: The coadministration of L-dopa/benserazide resulted in a major increase in systemic exposure to L-dopa and 3-OMD and a decrease in L-dopa clearance. The compartmental model allowed an adequate description of the observed L-dopa and 3-OMD concentrations in the absence and presence of benserazide. It had an advantage over noncompartmental analysis because it could describe the ...
PURPOSE: To study the PK interaction of L-dopa/benserazide in rats. METHODS: Male rats received a single oral dose of 80 mg/kg L-dopa or 20 mg/kg benserazide or 80/20 mg/kg L-dopa/benserazide. Based on plasma concentrations the kinetics of L-dopa, 3-O-methyldopa (3-OMD), benserazide, and its metabolite Ro 04-5127 were characterized by noncompartmental analysis and a compartmental model where total L-dopa clearance was the sum of the clearances mediated by amino-acid-decarboxylase (AADC), catechol-O-methyltransferase and other enzymes. In the model Ro 04-5127 inhibited competitively the L-dopa clearance by AADC. RESULTS: The coadministration of L-dopa/benserazide resulted in a major increase in systemic exposure to L-dopa and 3-OMD and a decrease in L-dopa clearance. The compartmental model allowed an adequate description of the observed L-dopa and 3-OMD concentrations in the absence and presence of benserazide. It had an advantage over noncompartmental analysis because it could describe the ...
641738DNAHomo sapiensCDS(1)..(738) 1atg atg acg ggc tac aat aat ggt cgc tgt ccc cgg aat tct ctc tac 48Met Met Thr Gly Tyr Asn Asn Gly Arg Cys Pro Arg Asn Ser Leu Tyr1 5 10 15agt gac tgc att att gag gag aag acg gtg gtc ctg cag aaa aaa gac 96Ser Asp Cys Ile Ile Glu Glu Lys Thr Val Val Leu Gln Lys Lys Asp 20 25 30aat gag ggc ttt gga ttc gtg ctt cga ggg gcc aaa gct gac aca ccc 144Asn Glu Gly Phe Gly Phe Val Leu Arg Gly Ala Lys Ala Asp Thr Pro 35 40 45att gaa gaa ttc aca cca aca ccg gct ttc cca gcc cta cag tac ctg 192Ile Glu Glu Phe Thr Pro Thr Pro Ala Phe Pro Ala Leu Gln Tyr Leu 50 55 60gag tcc gtg gat gaa ggt ggg gtg gcg tgg caa gcc gga cta agg acc 240Glu Ser Val Asp Glu Gly Gly Val Ala Trp Gln Ala Gly Leu Arg Thr65 70 75 80ggg gac ttc ttg att gag gtt aac aat gag aat gtt gtc aaa gtc ggc 288Gly Asp Phe Leu Ile Glu Val Asn Asn Glu Asn Val Val Lys Val Gly 85 90 95cac agg cag gtg gtg aac atg atc cgg cag gga ggg aat cac ctg gtc 336His Arg Gln Val Val Asn Met Ile Arg Gln Gly Gly Asn His Leu Val 100 105 ...
Train on 50000 samples, validate on 10000 samples Epoch 1/20 50000/50000 [==============================] - 58s 1ms/step - loss: 3.0416 - acc: 0.2552 - mean_squared_error: 0.0086 - val_loss: 3.2335 - val_acc: 0.2305 - val_mean_squared_error: 0.0089 Epoch 2/20 50000/50000 [==============================] - 58s 1ms/step - loss: 2.9324 - acc: 0.2783 - mean_squared_error: 0.0085 - val_loss: 3.1399 - val_acc: 0.2471 - val_mean_squared_error: 0.0087 Epoch 3/20 50000/50000 [==============================] - 58s 1ms/step - loss: 2.8245 - acc: 0.3031 - mean_squared_error: 0.0083 - val_loss: 3.1052 - val_acc: 0.2639 - val_mean_squared_error: 0.0086 Epoch 4/20 50000/50000 [==============================] - 58s 1ms/step - loss: 2.7177 - acc: 0.3186 - mean_squared_error: 0.0081 - val_loss: 3.0722 - val_acc: 0.2696 - val_mean_squared_error: 0.0086 Epoch 5/20 50000/50000 [==============================] - 58s 1ms/step - loss: 2.6060 - acc: 0.3416 - mean_squared_error: 0.0079 - val_loss: 2.9785 - val_acc: ...
namespace OpenSSL; class BigNum { public function __construct(int,string $initval = 0); static public function createFromBinary(string $bin): BigNum; public function add(BigNum $val): BigNum; public function sub(BigNum $val): BigNum; public function mul(BigNum $val): BigNum; public function div(BigNum $val): array; /* tuple(BigNum $quotient, BigNum $remainder) */ public function intdiv(BigNum $val): BigNum; public function mod(BigNum $val): BigNum; public function pow(BigNum $exp): BigNum; public function powmod(BigNum $exp, BigNum $mod): BigNum; public function cmp(BigNum $val): int; /* trinary compare */ public function gcd(BigNum $val): BigNum; /* Greatest Common Divisor */ public function shr(int $bits): BigNum; public function shl(int $bits): BigNum; public function toDec(): string; public function toHex(): string; public function toBin(): string; public function __toString() { return $this-,toDec(); } public function __debugInfo() { return [ dec =, $this-,toDec(), hex =, $this-,toHex ...
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Entacapone is a catechol -o methyl trasnferase inhibitor. Entacapone is useful as an adjunct in patient currently on carbidopa and levodopa therapy. Entacapone will synergies the levodopa and carbidopa anti parkinsonian effects.
When used with carbidopa and levodopa (Atamet, Parcopa, Sinemet), entacapone increases levels of levodopa in the body. Entacapone is used together with carbidopa and levodopa to treat wearing-off symptoms of Parkinsons disease, such as stiffness, tremors, muscle spasms, and poor muscle control. Entacapone may also be...
The last chapter is entirely new, and features how the techniques of computational organic chemistry, as discussed in the previous eight chapters, can be employed toward explicating enzymatic reactions. The chapter is not an in-depth survey of all of the activities in computational enzyme action - that would require its own full-length book - but rather its an overview to inspire you. The chapter begins with a brief discussion of enzymatic models, including the Pauling paradigm and Goodmans model. Then computational strategies for addressing the large molecules involved in enzymatic studies are presented including QM/MM, adiabatic mapping, and the use of some very large-scale computations as benchmarks. Next, I present two case studies: of chorismate mutase and of catechol-O-methyltransferase (COMT). The chapter ends with a presentation of the progress in de novo design of enzymes capable of catalyzing specific reactions as developed by Baker and Houk.. ...
Do NOT use Parnate if: you are allergic to any ingredient in Parnate you have a history of stroke, heart disease, congestive heart failure, a brain disease, headaches, liver disease or abnormal liver function tests, high blood pressure, or an adrenal gland tumor (pheochromocytoma) you will be having surgery you eat foods with a high tyramine content (eg, aged cheeses, sour cream, red wines, beer, bologna, pepperoni, salami, summer sausage, pickled herring, liver, meat prepared with tenderizers, canned figs, raisins, bananas, avocados, soy sauce, fava beans, yeast extracts). Ask your health care provider for a complete list of foods you should avoid. you drink alcohol or consume large quantities of foods or drinks that contain caffeine (eg, coffee, tea, chocolate, cola) you are taking an amphetamine, an anorexiant (eg, sibutramine, phentermine), an antihistamine (eg, loratadine), apraclonidine, bupropion, buspirone, a catechol-O-methyltransferase (COMT) inhibitor (eg, entacapone), ...
2.1.1.1 Nicotinamide N-methyltransferase 2.1.1.2 Guanidinoacetate N-methyltransferase 2.1.1.3 Thetin--homocysteine S-methyltransferase 2.1.1.4 Acetylserotonin O-methyltransferase 2.1.1.5 Betaine--homocysteine S-methyltransferase 2.1.1.6 Catechol O-methyltransferase 2.1.1.7 Nicotinate N-methyltransferase 2.1.1.8 Histamine N-methyltransferase 2.1.1.9 Thiol S-methyltransferase 2.1.1.10 Homocysteine S-methyltransferase 2.1.1.11 Magnesium protoporphyrin IX methyltransferase 2.1.1.12 Methionine S-methyltransferase 2.1.1.13 Methionine synthase 2.1.1.14 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase 2.1.1.15 Fatty-acid O-methyltransferase 2.1.1.16 Methylene-fatty-acyl-phospholipid synthase 2.1.1.17 Phosphatidylethanolamine N-methyltransferase 2.1.1.18 Polysaccharide O-methyltransferase 2.1.1.19 Trimethylsulfonium--tetrahydrofolate N-methyltransferase 2.1.1.20 Glycine N-methyltransferase 2.1.1.21 Methylamine--glutamate N-methyltransferase 2.1.1.22 Carnosine N-methyltransferase ...
Our findings strongly suggest that the inhibitory effects of estradiol on GMC growth are mediated via CYP450-derived metabolites. Treatment of GMCs with estradiol, 2-hydroxyestradiol, or 2-methoxyestradiol, but not estrone, estriol, 16α-hydroxyestradiols, estrone sulfate, hydroxyestrone, or methoxyestrone, inhibits serum-induced GMC growth, and 2-hydroxyestradiol or 2-methoxyestradiol are more potent than estradiol in this regard. Importantly, 3-methylcholantherene and phenobarbital, CYP450 inducers12 with no affinity for ERs, enhanced the inhibitory effects of estradiol. Moreover, 1-aminobenzotriazole, a broad spectrum CYP450 inhibitor13 with no affinity for ERs,6 abrogated the antigrowth effects of estradiol both in the presence and absence of CYP450 inducers (see schematic representation in Figure 1). Our conclusion that the inhibitory effects of estradiol on GMC growth are mediated via CYP450-derived metabolites is further supported by the well-established findings that the CYP1A1 and ...
Wheat (Triticum aestivum) O-methyltransferase (TaOMT2) catalyzes the sequential methylation of the flavone,tricetin (5,7,3,4,5-pentahydroxyflavone) to its 3-methyl-(selgin), 3,5-dimethyl-(tricin) and 3,4,5-trimethyl ether derivatives, although tricin is the major product of this reaction. The novelty of TaOMT2 to perform three sequential methylations of tricetin as a substrate, the chemopreventive properties of its major product, tricin, and the compelling interest in the proteins structure-function relationships, prompted us to further investigate this novel protein at the biochemical, molecular and structural levels. A 3-D model of this protein was constructed using the crystal structure of the highly homologous Medicago sativa caffeic acid/5-hydroxyferulic acid O-methyltransferase (MsCOMT) as a template with the aim of proposing a mechanism for multiple methyl transfer reactions in wheat. Homology modeling experiments in which each of the substrates tricetin, selgin and tricin, was ...
... whose formation is catalyzed by O-methyltransferases that act on phenols, e.g., Catechol-O-methyl transferase (COMT). A large ... number of natural products in plants, e.g. lignins, are generated via catalysis by caffeoyl-CoA O-methyltransferase. Organic ...
... is a major metabolite of L-3,4-dihydroxyphenylalanin (L-DOPA) and is formed by catechol O-methyltransferase ( ... This process is catalyzed by catechol O-methyltransferase methylates (COMT). The action of the enzyme makes it possible the ... Tai, C. H.; Wu, R. M. (2002). "Catechol-O-methyltransferase and Parkinson's disease". Acta medica Okayama. 56 (1): 1-6. PMID ... L-DOPA Entacapone Tolcapone Catechol-O-methyl transferase Parkinson's disease Parkinson's Disease and movement disorders. ...
... is not metabolized by catechol-O-methyltransferase. The plasma half-life measured after oral administration is about ...
2012). "Catechol-O-methyltransferase in complex with substituted 3′-deoxyribose bisubstrate inhibitors". Acta Crystallographica ... Manikumar, G.; Jin, C.; Rehder, K. S. (2008). "Convenient Synthesis of Tolcapone, a Selective Catechol‐O‐methyltransferase ... a novel inhibitor of catechol-O-methyltransferase". British Journal of Clinical Pharmacology. 48 (4): 513-520. doi:10.1046/j. ... potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-O-methyltransferase (COMT). It has demonstrated ...
... as a substrate for catechol-o-methyltransferase". Z. Naturforsch. C (in German). 31 (5-6): 280-284. PMID 134569. ... through incubation with rat liver catechol-O-methyltransferase. Umbelliferone "Aesculetin". Sigma-Aldrich. Dey, P. M.; Harborne ...
... is a selective and reversible inhibitor of the enzyme catechol-O-methyltransferase (COMT). When taken together with ... Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT eliminates biologically active ... entacapone stops catechol-O-methyltransferase from breaking down and metabolizing levodopa, resulting in an overall increase of ... catechols present in catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When ...
The meta-hydroxyl group of catechol is methylated by catechol-O-methyltransferase. Four of the five hydroxyl groups of ...
... catechol-O-methyltransferase) gene related to dopamine release are found to be critical in the placebo effect among the ... "Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome". PLoS ONE. 7 (10): ...
... is a pharmaceutical drug acting as a catechol-O-methyltransferase (COMT) inhibitor. It is administered together with ... Opicapone blocks the enzyme catechol-O-methyltransferase (COMT) effectively (>90% at therapeutic doses), selectively and ...
It can inhibit 2-hydroxy and 4-hydroxyestradiol methylation by catechol-O-methyltransferase. It potently and specifically ...
"A catechol-O-methyltransferase that is essential for auditory function in mice and humans". Proceedings of the National Academy ... which is a transmembrane catechol-O-methyltransferase and is called LRTOMT2, TOMT or COMT2. The COMT2 is essential for auditory ... Leucine rich transmembrane and O-methyltransferase domain containing is a protein that in humans is encoded by the LRTOMT gene ... Leucine rich transmembrane and O-methyltransferase domain containing". Riahi Z, Bonnet C, Zainine R, Louha M, Bouyacoub Y, ...
"Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the rat". European Journal of ... Nitecapone (INN; OR-462) is a drug which acts as a selective inhibitor of the enzyme catechol O-methyl transferase (COMT). It ...
"A catechol-O-methyltransferase that is essential for auditory function in mice and humans". Proceedings of the National Academy ...
Gogos, J. A; Morgan, M; Luine, V; Santha, M; Ogawa, S; Pfaff, D; Karayiorgou, M (1998). "Catechol-O-methyltransferase-deficient ...
Catechol O-methyltransferase; PNMT: Phenylethanolamine N-methyltransferase ... tyramine N-methyltransferase in the second, and N-methyl-tyramine-β-hydroxylase in the third.[30][31] This pathway differs from ... and the conversion of octopamine to synephrine by phenylethanolamine N-methyltransferase.[25][30] ...
It is a single nucleotide polymorphism (SNP) in the COMT gene that codes catechol-O-Methyltransferase. The single nucleotide ... "A possible association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and the personality trait ... "An association study of catechol-O-methyltransferase and monoamine oxidase A polymorphisms and personality traits in Koreans". ... "Association of the functional catechol-O-methyltransferase VAL158MET polymorphism with the personality trait of extraversion". ...
4.*Marbach, J.J., and Levitt, M., Catechol_o_Methyl_Transferase Activity in TMJ Patients. J. Dent. Res. 54, 1975. 5.Lipton, J ... 11.*Marbach, J.J., and Levitt, M., Erythrocyte Catechol_o_Methyl_Transferase Activity in Facial Pain Patients. Journal Dental ...
Catechol-O-methyl transferase (COMT) is an enzyme that catalyzes the extraneuronal breakdown of catecholamines. The gene that ...
A COMT inhibitor is a drug that inhibits the action of catechol-O-methyl transferase. This enzyme is involved in degrading ...
Yavich L, Forsberg MM, Karayiorgou M, Gogos JA, Männistö PT (Sep 2007). "Site-specific role of catechol-O-methyltransferase in ...
... is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is ...
"Polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase genes: a study on fibromyalgia susceptibility". ...
"Evidence of epistasis between the catechol-O-methyltransferase and aldehyde dehydrogenase 3B1 genes in paranoid schizophrenia ...
Entacapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor that increases the bioavailability of ...
However, the 4-hydroxy group makes it susceptible to metabolism by catechol-O-methyl transferase (COMT). Since it is β2- ...
... 's efficacy in improving vigor and well-being in sleep deprivation subjects is dependent on catechol-O-methyl transferase ... catechol-O-methyltransferase genotype modulates waking functions but not recovery sleep". Clinical Pharmacology and ...
... kanggo dieliminasi kanti pira-pira prosès kaya ta metilasi kanti enzim catechol-o-methyltransferase, hidroksilasi, oksidasi, ...
Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE (Aug 2009). "Monoamine oxidase a and catechol-o-methyltransferase ...
1980) Catechol-O-methyltransferase activity: a determinant of levodopa response. Clin Pharmacol Ther 28:278-286. ... 1994) Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. Neurology ... Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma ... Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in ...
Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in ... L-DOPA biotransformation: Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with ... T2 - Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways ... L-DOPA biotransformation : Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities ...
Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A. (2004). The catechol-O-methyltransferase polymorphism: Relations to ... T1 - The catechol-O-methyltransferase polymorphism. T2 - Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric ... Bilder, RM, Volavka, J, Lachman, HM & Grace, AA 2004, The catechol-O-methyltransferase polymorphism: Relations to the tonic- ... Bilder, Robert M. ; Volavka, Jan ; Lachman, Herbert M. ; Grace, Anthony A. / The catechol-O-methyltransferase polymorphism : ...
Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and ... Adolescent, Adult, Benzophenones, Catechol O-Methyltransferase, Catechol O-Methyltransferase Inhibitors, Cognition, Double- ... COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition. ... BACKGROUND: Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity ...
N2 - Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau ... AB - Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau ... Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau). ... abstract = "Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than ...
... and various drugs and substances having a catechol structure. In humans, catechol-O-methyltransferase protein is encoded by the ... Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, Wang HY, Feng GY, St Clair D, He L (January 2005). "Catechol-O-methyltransferase gene ... Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines (such as dopamine, ... Catechol O-Methyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular and Cellular ...
Structural mechanism of S-adenosyl methionine binding to catechol O-methyltransferase.. Tsao D1, Diatchenko L, Dokholyan NV. ... Using catechol O-methyltransferase (COMT) as a model, we perform discrete molecular dynamics and computational docking ... Methyltransferases possess a homologous domain that requires both a divalent metal cation and S-adenosyl-L-methionine (SAM) to ... The proposed mechanism enables a general understanding of how divalent metal cations contribute to methyltransferase function. ...
X-ray Crystal Structure of a Bisubstrate Inhibitor Bound to the Enzyme Catechol-O-methyltransferase: A Dramatic Effect of ... CATECHOL O-METHYLTRANSFERASE, SOLUBLE FORM A 221 Rattus norvegicus EC#: 2.1.1.6 IUBMB Gene Name(s): Comt ...
Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine.. Benedetti F1, ... The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) ...
Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk. Katja Mitrunen, Nadejda Jourenkova, Vesa Kataja, Matti ... Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk. Katja Mitrunen, Nadejda Jourenkova, Vesa Kataja, Matti ... Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk. Katja Mitrunen, Nadejda Jourenkova, Vesa Kataja, Matti ... Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk Message Subject (Your Name) has forwarded a page to you ...
Inhibitors of Catechol-O-Methyltransferase. Author(s): James C. Barrow. Lieber Institute for Brain Development, 336 John G. ... Keywords:Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinsons disease, nitrocatechol, MB-COMT, SAM Binding, HPLC, ... Keywords: Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinsons disease, nitrocatechol, MB-COMT, SAM Binding, HPLC ... Since the identification of Catechol-O-Methyltransferase (COMT) by Axelrod in 1957, many inhibitors of this enzyme have been ...
PubMed journal article Catechol-O-methyltransferase Val158Met polymorphism (rs4680) is associated with pain in multiple ... AdultAllelesCatechol O-MethyltransferaseFemaleGenetic Predisposition to DiseaseGenotypeHumansMaleMethionineMiddle AgedMultiple ... "Catechol-O-methyltransferase Val158Met Polymorphism (rs4680) Is Associated With Pain in Multiple Sclerosis." The Journal of ... Catechol-O-methyltransferase Val158Met Polymorphism (rs4680) Is Associated With Pain in Multiple Sclerosis. J Pain. 2013;14(12 ...
Lack of Association of Alcohol Dependence and Habitual Smoking With Catechol-O-methyltransferase. Authors. *. Tatiana Foroud,. ... Objective: To test whether variation in the gene encoding the enzyme catechol-O-methyltransferase (COMT), which catalyzes the ... Lack of Association of a Functional Catechol-O-Methyltransferase Gene Polymorphism With Risk of Tobacco Smoking: Results From a ... The lack of association between catechol-O-methyl-transferase Val108/158Met polymorphism and smoking in schizophrenia and ...
Catechol-O-methyltransferase (COMT), an enzyme that is involved in the degradation of catecholamine neurotransmitters (e.g., ... 2005). Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations. ... 2004). Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme ... 1996). Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo- ...
COMT (catechol-O-methyltransferase) is an enzyme which inactivates catechols, including the significant neurotransmitters ... Genetic contribution of catechol-o-methyltransferase variants in treatment outcome of low back pain: a prospective genetic ... Catechol-O-methyltransferase (COMT) codes for a protein which is important in catabolic pathways of a number of pain-relevant ... Rakvåg TT, Ross JR, Sato H, Skorpen F, Kaasa S, Klepstad P. Genetic variation in the catechol-O-methyltransferase (COMT) gene ...
Showing Protein Catechol O-methyltransferase (HMDBP00272). IdentificationBiological propertiesGene propertiesProtein properties ... Rutherford K, Le Trong I, Stenkamp RE, Parson WW: Crystal structures of human 108V and 108M catechol O-methyltransferase. J Mol ... Bertocci B, Miggiano V, Da Prada M, Dembic Z, Lahm HW, Malherbe P: Human catechol-O-methyltransferase: cloning and expression ... Ulmanen I, Lundstrom K: Cell-free synthesis of rat and human catechol O-methyltransferase. Insertion of the membrane-bound form ...
No difference in the distribution of the catechol-O-methyltransferase genotypes (H/H, H/L, L/L) and alleles (H, L) was observed ... Catechol-O-methyltransferase, which has a functional genetic polymorphism, plays an important role in dopamine metabolism. The ... Association study of catechol-O-methyltransferase gene polymorphism in Korean male alcoholics. ... Polymerase chain reaction-based genotyping was used to verify the presence of the catechol-O-methyltransferase gene ...
catechol-O-methyltransferase (COMT), Sequence Homology Amino Acid, enzmes. patent number. WO1991011513 A3. language. English. ... Catechol-o-methyltransferase, polypeptide sequences and dna molecule coding therefor. Jalanko, Anu; Kalkkinen, Nisse; Lundström ... catechol-O-methyltransferase (COMT),Sequence Homology Amino Acid,enzmes}, language = {eng}, month = {10}, note = {Patent, ... Catechol-o-methyltransferase, polypeptide sequences and dna molecule coding therefor}, year = {1991}, } ...
Catechol-O-methyltransferase (COMT) metabolizes catecholamines (Männisto and Kaakkola, 1999). The human COMT gene contains a ... Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat ... Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat ... Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat ...
Catechol-O-methyltransferase (COMT) plays an essential role in detoxification of catechols by transferring the methyl group ... Catechol-O-methyltransferase: a dual-role player in different breast cancer subtypes?. Autoři. JANÁČOVÁ Lucia FAKTOR Jakub ... Catechol-O-methyltransferase: a dual-role player in different breast cancer subtypes? ...
Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J Neurosci. 2003;23:2008-2013. [PubMed] ... catechol O-methyl transferase. Hif-1α. hypoxia-inducible factor 1alpha. Iba1. ionized calcium-binding adaptor molecule 1. SMRT ... Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M. Catechol-O-methyltransferase-deficient mice exhibit ... TRAUMATIC BRAIN INJURY STIMULATES HIPPOCAMPAL CATECHOL-O-METHYL TRANSFERASE EXPRESSION IN MICROGLIA. John B. Redell and Pramod ...
By Celina Scott in Catechol methyltransferase April 19, 2017. IL-6 is a secreted cytokine that functions through binding two ... By Celina Scott in Catechol methyltransferase May 3, 2017. Diabetes is a chronic metabolic disease that impacts a substantial ... By Celina Scott in Catechol methyltransferase June 5, 2017. SLAMF9 is an associate from the signaling lymphocyte-activating ... By Celina Scott in Catechol methyltransferase May 21, 2017. Bariatric surgery is now very common & most physicians shall ...
Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine ... Catechol O-Methyltransferase / genetics*. China. Cohort Studies. Genetic Predisposition to Disease. Genotype. Humans. Logistic ... Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking ... RATIONALE: Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the ...
Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major Depressive Disorder (MDD). ... Title:Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major Depressive Disorder ( ... Neslihan Aygun Kocabas, "Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major ... Keywords:COMT gene, pharmacogenetics, antidepressant, treatment response, snp, Catechol O Methyl Transferase, Major Depressive ...
Background: The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked ... No association between catechol-o-methyltransferase Val108/158Met polymorphism and schizophrenia or its clinical symptomatology ... Catechol-O-methyltransferase (COMT) polymorphisms predict treatment response in electroconvulsive therapy. Anttila, Sami; ... Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trø ...
  • They are mainly inactivated by COMT, 3 a Phase II enzyme that methylates catechol estrogens to less polar monomethyl ethers, which can then be excreted. (aacrjournals.org)
  • Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol. (testcatalog.org)
  • This relationship led us to postulate that oxidation of the carcinogenic 4-hydroxy catechol estrogens (CE) of estrone (E 1 ) and estradiol (E 2 ) to catechol estrogen-3,4-quinones (CE-3, 4-Q) results in electrophilic intermediates that covalently bind to DNA to form depurinating adducts. (pnas.org)
  • This relationship led us to postulate that oxidation of catechol estrogens (CE) to CE quinones (CE-Q) results in electrophilic intermediates that also covalently bind to DNA and form depurinating adducts. (pnas.org)
  • No difference in the distribution of the catechol-O-methyltransferase genotypes (H/H, H/L, L/L) and alleles (H, L) was observed between the patients and the controls. (ovid.com)
  • Borgulya J, Bruderer H, Bernauer K, Zürcher G, Da Prada M (1989) Catechol-O-methyltransferase-inhibiting pyrocatechol derivatives - synthesis and structure activity studies. (springer.com)