A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
An enzyme that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA.
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.
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.
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.
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.
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.
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.
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)
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.
Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.
Enzymes that catalyze the S-adenosyl-L-methionine-dependent methylation of ribonucleotide bases within a transfer RNA molecule. EC 2.1.1.
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)
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.
Methylases that are specific for CYTOSINE residues found on DNA.
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.
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.
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.
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.
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.
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.
5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
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.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.-.
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).
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.
An antiseptic and disinfectant aromatic alcohol.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
A species of halophilic archaea whose organisms are nonmotile. Habitats include freshwater and marine mud, animal-waste lagoons, and the rumens of ungulates.
An enzyme that catalyses three sequential METHYLATION reactions for conversion of phosphatidylethanolamine to PHOSPHATIDYLCHOLINE.
Benzoate derivatives substituted by one or more hydroxy groups in any position on the benzene ring.
This enzyme catalyzes the last step of CREATINE biosynthesis by catalyzing the METHYLATION of guanidinoacetate to CREATINE.
A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants.
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.
Mold and yeast inhibitor. Used as a fungistatic agent for foods, especially cheeses.
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.
Cyclic TETRAPYRROLES based on the corrin skeleton.
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.
An essential amino acid. It is often added to animal feed.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
A pyrimidine base that is a fundamental unit of nucleic acids.
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.
Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.
Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.
The rate dynamics in chemical or physical systems.
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.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
A species of gram-negative, aerobic bacteria isolated from soil and water as well as clinical specimens. Occasionally it is an opportunistic pathogen.
A fungistatic compound that is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid.
The functional hereditary units of BACTERIA.
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 used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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.
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.
Proteins found in any species of bacterium.
Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
A trihydroxybenzene or dihydroxy phenol that can be prepared by heating GALLIC ACID.
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.
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.
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).
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)
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.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
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 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.
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.
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).
Proteins prepared by recombinant DNA technology.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A widely used industrial solvent.
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.
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.
Estrone derivatives substituted with one or more hydroxyl groups in any position. They are important metabolites of estrone and other estrogens.
A cell line derived from cultured tumor cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
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)
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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)
Benzoic acid or benzoic acid esters substituted with one or more chlorine atoms.
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.
The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.
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.
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.
An enzyme that catalyzes the demethylation of L-homocysteine to L-METHIONINE.
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 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.
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)
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.
A genus of gram-negative bacteria of the family MORAXELLACEAE, found in soil and water and of uncertain pathogenicity.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
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.
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.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
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.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.
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.
A class of enzymes that transfers nucleotidyl residues. EC 2.7.7.
A bacterial genus of the order ACTINOMYCETALES.
Nucleosides in which the base moiety is substituted with one or more sulfur atoms.
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.
Low-molecular-weight compounds produced by microorganisms that aid in the transport and sequestration of ferric iron. (The Encyclopedia of Molecular Biology, 1994)
Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
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.
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.
A pyrimidine nucleoside that is composed of the base CYTOSINE linked to the five-carbon sugar D-RIBOSE.
A species of gram-negative hyperthermophilic ARCHAEA found in deep ocean hydrothermal vents. It is an obligate anaerobe and obligate chemoorganotroph.
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.
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.
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.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
Proteins found in any species of archaeon.
Constituent of 50S subunit of prokaryotic ribosomes containing about 3200 nucleotides. 23S rRNA is involved in the initiation of polypeptide synthesis.
A species of gram-negative bacteria in the genus PSEUDOMONAS, which is found in SOIL and WATER.
A family of nonmetallic, generally electronegative, elements that form group 17 (formerly group VIIa) of the periodic table.
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.
A sulfur-containing essential L-amino acid that is important in many body functions.
Pigment obtained by the oxidation of epinephrine.
Salts and esters of gentisic acid.
Formation of an acetyl derivative. (Stedman, 25th ed)
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
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.
An enzyme that catalyzes the METHYLATION of GLYCINE using S-ADENOSYLMETHIONINE to form SARCOSINE with the concomitant production of S-ADENOSYLHOMOCYSTEINE.
The small subunit of eubacterial RIBOSOMES. It is composed of the 16S RIBOSOMAL RNA and about 23 different RIBOSOMAL PROTEINS.
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.
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)
Chromosome regions that are loosely packaged and more accessible to RNA polymerases than HETEROCHROMATIN. These regions also stain differentially in CHROMOSOME BANDING preparations.
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.
Elements of limited time intervals, contributing to particular results or situations.
An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.
A methylated metabolite of norepinephrine that is excreted in the urine and found in certain tissues. It is a marker for tumors.
Proteins obtained from ESCHERICHIA COLI.
The sum of the weight of all the atoms in a molecule.
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.
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.
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)
The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.
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.
An essential amino acid that is physiologically active in the L-form.
Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)
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)
A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or 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.
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.
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)
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.
A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.
Drug metabolizing enzymes which oxidize methyl ethers. Usually found in liver microsomes.
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.
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.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
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.
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.
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)
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).
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
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.
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).
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.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
A class of weak acids with the general formula R-CONHOH.
Inorganic salts of sulfurous acid.
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)
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.
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.
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)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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 - Contribution of catechol O-methyltransferase to the removal of accumulated interstitial catecholamines evoked by myocardial ischemia. AU - Kuroko, Yosuke. AU - Fujii, Takafumi. AU - Yamazaki, Toji. AU - Akiyama, Tsuyoshi. AU - Ishino, Kozo. AU - Sano, Shunji. AU - Mori, Hidezo. N1 - Funding Information: This work was supported by Grands-in-Aid for scientific research (15590787) from the Ministry of Education, Culture, Sports, Science and Technology. The authors thank Orion-Pharma (Espoo, Finland) for the supply of entacapone.. PY - 2005/11/11. Y1 - 2005/11/11. N2 - Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. Although myocardial ischemia evokes similar excessive catecholamine accumulation, it is uncertain whether COMT activity is involved in the removal of accumulated catecholamines evoked by myocardial ischemia. We examined how COMT activity affects myocardial catecholamine levels during myocardial ischemia and ...
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
Catechol-O-methyltransferase (COMT Val158Met) has been implicated in both depression and cardiovascular disease. The purpose of this study was to assess if COMT Val158Met, which influences the COMT enzyme activity, has an effect on the risk of cardiovascular disease (CVD) in individuals with a history of depression and also to determine if the risk differs depending on gender. Data from a longitudinal cohort study of mental health among Swedish adults was used. Depression was assessed twice 3 years apart for each participant, in 1998-2001 and 2001-2003. Saliva DNA was contributed by 4349 (41.7%) of the participants and 3525 was successfully genotyped for COMT Val158Met. Participants were followed up until December 2014 from the National Patient register with regard to cardiovascular outcomes (hypertensive or ischemic heart disease, and stroke). Those with depression and the high COMT enzyme activity genotype (Val/Val) had almost a three-fold increased risk of later CVD (OR 3.6; 95% CI: 2.0-6.6) compared
The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene affects activity of the enzyme and influences performance and efficiency of the prefrontal cortex (PFC); however, although catecholaminergic neurotransmission is implicated, the underlying mechanisms remain elusive because studies of the role of COMT in PFC function are sparse. This study investigated the effect of tolcapone, a brain-penetrant COMT inhibitor, on a rat model of attentional set shifting, which is dependent on catecholamines and the medial PFC (mPFC). Additionally, we investigated the effect of tolcapone on extracellular catecholamines in the mPFC using microdialysis in awake rats. Tolcapone significantly and specifically improved extradimensional (ED) set shifting. Tolcapone did not affect basal extracellular catecholamines, but significantly potentiated the increase in extracellular dopamine (DA) elicited by either local administration of the depolarizing agent potassium chloride or systemic administration
Metabolites of entacapone, (E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl) propenamide, a potent inhibitor of catechol-O-methyltransferase, were isolated from dog urine. After hydrolysis of glucuronides and sulfates, 5 metabolites were identified in addition to unchanged entacapone by HPLC w …
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 ...
Catechol-O-methyl transferase Catechol-O-methyltransferase Identifiers Symbol(s) COMT; External IDs OMIM: 116790 MGI: 88470 Homologene: 30982
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity. In this study, we aimed to clarify the relationships between the catechol-O-methyltransferase (COMT) gene Val158Met (rs4680) polymorphism and development, functional and clinical status of CTS. Ninetyfive women with electro diagnostically confirmed CTS and 95 healthy controls were enrolled in the study. The functional and clinical status of the patients was measured by the Turkish version of the Boston Questionnaire and intensity of pain related to the past 2 weeks was evaluated on a visual analog scale (VAS). The Val158Met polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), method. We divided patients according to the genotypes of the Val158Met polymorphism as Val/Val, Val/Met and Met/Met. There were not any significant differences in terms of Val158Met polymorphisms between patients and healthy controls (p >0.05). We also did not find ...
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 ...
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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 ...
OBJECTIVE: A valine/methionine polymorphism in the catechol O-methyltransferase (COMT) gene has been proposed to influence susceptibility to schizophrenia, as has a COMT haplotype in Ashkenazi Jewish and Irish subjects. The authors examined these hypotheses. METHOD: They reviewed data from more than 2,800 individuals, including almost 1,200 with schizophrenia, from case-control and family-based European association samples. RESULTS: The authors found no support for the hypothesis that a valine/methionine polymorphism in the COMT gene influences susceptibility to schizophrenia or the hypothesis that a COMT haplotype influences susceptibility to schizophrenia in Ashkenazi Jewish and Irish subjects. CONCLUSIONS: The data suggest that the valine allele of COMT does not increase susceptibility to schizophrenia in Europeans and that the Ashkenazi or Irish haplotype does not increase susceptibility. Ethnic variation in the linkage disequilibrium structure at COMT means that the haplotype data may not ...
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 ...
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Decaffeinated GTE was not associated with reductions in body weight, BMI, or WC and did not alter energy intake or mean hormone concentrations in healthy postmenopausal women over 12 mo. GTE decreased fasting insulin concentrations in those with elevated baseline fasting concentrations. The high-act …
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) ...
Conjugation of a structurally diverse set of 53 catechol compounds was studied in vitro using six recombinant human sulfotransferases (SULTs), five UDP-glucuronosyltransferases (UGT) and the soluble form of catechol O-methyltransferase (S-COMT) as catalyst. The catechol set comprised endogenous compounds, such as catecholamines and catecholestrogens, drugs, natural plant constituents, and other catechols with diverse substituent properties and substitution patterns. Most of the catechols studied were substrates of S-COMT and four SULT isoforms (1A1, 1A2, 1A3, and 1B1), but the rates of conjugation varied considerably, depending on the substrate structure and the enzyme form. SULT1E1 sulfated fewer catechols. Only low activities were observed for SULT1C2. UGT1A9 glucuronidated catechols representing various structural classes, and almost half of the studied compounds were glucuronidated at a high rate. The other UGT enzymes (1A1, 1A6, 2B7, and 2B15) showed narrower substrate specificity for ...
TY - JOUR. T1 - MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls. AU - Walton, Esther. AU - Liu, Jingyu. AU - Hass, Johanna. AU - White, Tonya. AU - Scholz, Markus. AU - Roessner, Veit. AU - Gollub, Randy. AU - Calhoun, Vince D. AU - Ehrlich, Stefan. PY - 2014/8. Y1 - 2014/8. N2 - Many genetic studies report mixed results both for the associations between COMT polymorphisms and schizophrenia and for the effects of COMT variants on common intermediate phenotypes of the disorder. Reasons for this may include small genetic effect sizes and the modulation of environmental influences. To improve our understanding of the role of COMT in the disease etiology, we investigated the effect of DNA methylation in the MB-COMT promoter on neural activity in the dorsolateral prefrontal cortex during working memory processing as measured by fMRI - an intermediate phenotype for schizophrenia. Imaging and epigenetic data were measured in ...
Background. Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7-11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise.. Methods. 93 unrelated patients with chronic LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with lumbar fusion (N = 60) or cognitive therapy and exercises (N = 33). Standardised questionnaires assessing the ODI, VAS LBP, psychological factors and use of analgesics, were answered by patients both at baseline and at 7-11 years follow-up. Four SNPs in the COMT gene were successfully genotyped. Single ...
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 ...
TY - JOUR. T1 - Association between the catechol-O-methyltransferase (rs4680. T2 - Val158Met) polymorphism and serum alanine aminotransferase activity. AU - Hiyoshi, Mineyoshi. AU - Uemura, Hirokazu. AU - Arisawa, Kokichi. AU - Nakamoto, Mariko. AU - Hishida, Asahi. AU - Okada, Rieko. AU - Matsuo, Keitaro. AU - Kita, Yoshikuni. AU - Niimura, Hideshi. AU - Kuriyama, Nagato. AU - Nanri, Hinako. AU - Ohnaka, Keizo. AU - Suzuki, Sadao. AU - Mikami, Haruo. AU - Kubo, Michiaki. AU - Tanaka, Hideo. AU - Hamajima, Nobuyuki. N1 - Funding Information: This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas of Cancer (No. 17015018 ) and on Innovative Areas (No. 221S0001 ) from the Japanese Ministry of Education, Culture, Sports, Science and Technology . PY - 2012/4/1. Y1 - 2012/4/1. N2 - In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol- O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a ...
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 ...
Received within 4 weeks or planning to take during participation in the clinical study: any controlled-release LD product, additional CD (e.g., Lodosyn®) or benserazide (e.g. Serazide®), catechol-O-methyl transferase inhibitors (e.g., entacapone and tolcapone), nonselective MAO inhibitors, apomorphine, and antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder ...
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. ...
There is evidence that altering stress mindset-the belief that stress is enhancing vs. debilitating-can change cognitive, affective and physiological responses to stress. However individual differences in responsiveness to stress mindset manipulations have not been explored. Given the previously established role of catecholamines in both placebo effects and stress, we hypothesized that genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, would moderate responses to an intervention intended to alter participants mindsets about stress. Participants (N = 107) were exposed to a stress mindset manipulation (videos highlighting either the enhancing or debilitating effects of stress) prior to engaging in a Trier Social Stress task and subsequent cognitive tasks. The associations of the COMT rs4680 polymorphism with the effect of stress mindset video manipulations on cognitive and affective responses were examined. Genetic variation at rs4680 modified the effects
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
A partially purified preparation of norepinephrine storage particles from the rat heart was studied in vitro. The particles were found to have dopamine β-oxidase activity, indicating that norepinephrine may be formed from dopamine in the storage granules as well as taken up from the cytoplasm of the cell. ATP was found in the particles in the same molar ratio to norepinephrine as has been previously described in adrenal chromaffin granules, and could serve to form a storage complex with the amine. There were only trace amounts of catechol-O-methyl transferase and monoamine oxidase in the preparation. The particles were most stable in solutions at 4°C containing sucrose, magnesium or calcium, but retained about half their catecholamine content in sucrose at 23°C for 1 hour. Norepinephrine was released from the particles into free solution in media of low tonicity or pH, in the presence of the detergent sodium deoxycholate, and by high concentrations of reserpine, tyramine and cocaine. ...
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 ...
Inclusion Criteria:. Idiopathic Parkinsons disease , 7 years duration. Modified Hoehn and Yahr Scale Stages I through III. Age greater than or equal to 30 years old. Patients or their partners must use adequate contraceptive methods. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and do not plan on traveling extensively during the study. Exclusion Criteria:. Atypical Parkinsons disease syndromes due to drugs, metabolic disorders, encephalitis, or degenerative diseases.. Levodopa received for 1-year accumulated interval in the last two years.. Dopamine agonist medications or catechol-o-methyl transferase inhibitors in the 30 days prior to baseline.. Unstable dose regimes of hypnotics, anxiolytics or antidepressants. Dementia. History of stereotaxic brain surgery, psychosis or active epilepsy within past year.. Participation in clinical trial within the previous 30 days.. Malignant melanoma or history of ...
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.. ...
Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine D4 receptor (DRD4) genes are likely to impact directly on the functioning of the frontal cortex, whereas polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes might influence frontal cortex functioning indirectly via strong frontostriatal connections. A significant effect of the COMT valine(1)methionine (Val 158 Met) polymorphism was found. Infants with the Met/Met genotype were significantly less distractible than infants with the Val/Val genotype in Freeze-Frame trials presenting an engaging central stimulus. In addition, there was an interaction with the DAT1 3; variable number of tandem repeats polymorphism; the COMT effect was
TY - JOUR. T1 - Regulation of catechol-O-methyltransferase expression in human myometrial cells. AU - Wentz, Melissa J.. AU - Jamaluddin, Mohammad. AU - Garfield, Robert E.. AU - Al-Hendy, Ayman. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2006/12. Y1 - 2006/12. N2 - OBJECTIVE: The catechol-O-methyltransferase enzyme catalyzes the methylation of the catechol estrogens, 2- or 4-hydroxyestrogen, to 2- or 4-methoxyestrogen. Both the hydroxy estrogens and methoxy estrogens were shown to modulate the effects of estrogen. Because catechol-O-methyltransferase activity controls levels of these metabolites, it may help regulate the cellular estrogenic milieu. In this study, we examined the regulation of catechol-O-methyltransferase expression in human myometrial cells. METHODS: Catechol-O-methyltransferase expression was assessed by reverse transcription-polymerase chain reaction, Western blot, and luciferase assays in human myometrial cells after treatment with estrogen or ...
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 ...
Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism. Twelve Val/Val and eleven Met/Met healthy male subjects entered the study. Tolcapone 200 mg was administered in two weekly sessions, according to a balanced, crossover, double-blind, placebo-controlled design. PPI was assessed with 5 dB and 15 dB above background prepulses, at 30-, 60-, and 120 ms prepulse-pulse intervals. Subjects also underwent the n-back and the letter-number sequencing (LNS) tasks. PPI was lower in the Val/Val compared to the Met/Met group in the placebo condition. Tolcapone increased PPI significantly in the Val/Val group and tended to have the opposite effect in
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. ...
Some studies have reported associations between COMT and MAO genotypes and aggression, though results have been inconsistent. We examined the relationship between Overt aggression scale (OAS) scores, and both MAOA and MAOB polymorphisms in a well-powered sample of 346 subjects with schizophrenia. We also examined COMT in a Stage II replication sample of 150 individuals, and combined these results with our previously reported (Stage I) findings for COMT. We found no evidence of any associations between OAS ratings and any of the polymorphisms investigated under different genetic models. There was no evidence of epistatic interaction between MAOA and COMT on OAS scores. These results fail to support the theory that functional polymorphisms within the MAOA, MAOB, or COMT genes, as determinants of catecholamine enzymatic activity, are risk factors for aggressive behavior ...
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 ...
Milled wood lignins isolated from genetically modified poplar trees were studied by quantitative 31P NMR spectroscopy, in combination with thioacidolysis and mild alkaline hydrolysis. The genetictransformation of the trees included down regulation of CAD and COMT enzyme activities.These analyses confirmed that moderate CAD down-regulation does not substantially alter ligninstructure. In contrast, severe CAD deficiency alters the lignin structure more profoundly by decreasingthe syringyl/guaiacyl ratio and increasing the degree of condensation of the lignin. Themost severe alterations were observed in the lignins from the COMT-transformed lines ...
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 ...
The BDNF Val66Met polymorphism has been associated with sensitivity to stress and affective disorders. We therefore sought to model the inter-causality of these relationships under controlled laboratory conditions. We subjected humanized BDNF Val66Met (hBDNFVal66Met) transgenic mice to a history of stress, modeled by chronic late-adolescent corticosterone (CORT) exposure, before evaluating affective-related behavior using the forced-swim test (FST) in adulthood. While hBDNFMet/Met mice had a depression-like phenotype in the FST irrespective of CORT, hBDNFVal/Val wildtype mice had a resilient phenotype but developed an equally robust depressive-like phenotype following CORT. A range of stress-sensitive molecules were studied across the corticohippocampal axis, and where genotype differences occurred following CORT they tended to inversely coincide with the behavior of the hBDNFVal/Val group. Notably, tyrosine hydroxylase was markedly down-regulated in the mPFC of hBDNFVal/Val mice as a result of ...
The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. resonance tests. Based on earlier literature, our determined versions and in vitro outcomes claim that serotonin can be an inhibitor of COMT. Nevertheless, whether this inhibition offers biological significance cant be ascertained from these data only. Our structural model shows that serotonin inhibits COMT activity by positively contending with SAM in the energetic site. This system is definitely further backed by our kinetics research. We performed behavioral tests to see whether our model and in vitro data are predictive of in vivo results on discomfort behaviors. Mice pretreated with SAM shown diminishes serotonin-induced mechanised hypersensitivity (Number ?(Figure3A).3A). We hypothesize that the excess SAM generates this attenuation by reducing the likelihood of serotonin occupying the energetic site of COMT. The fairly modest anti-allodynic ...
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 ...
Insulin-Like-Growth Factor 1 Moderates the Influence of the BDNF P.Val66Met Variant on Depression Severity in Adolescent Depression. PubMed, SCI, Scopus, ESCI, PMC indexed
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) ...
... whose formation is catalyzed by O-methyltransferases that act on phenols, e.g., Catechol-O-methyl transferase (COMT). Many ... natural products in plants, e.g. lignins, are generated via catalysis by caffeoyl-CoA O-methyltransferase. Organic methoxides ...
... is produced by the methylation of L-DOPA by the enzyme catechol-O-methyltransferase. The necessary cofactor for ... 3-O-methyldopa is a major metabolite of L-3,4-dihydroxyphenylalanine (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 ...
"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 ... Catechol-O-methyltransferase inhibitor F.. Macdonald (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1635. ISBN 978 ...
... is not metabolized by catechol-O-methyltransferase. The plasma half-life measured after oral administration is about ...
... allelic polymorphism of the catechol-O-methyltransferase (COMT) gene; increased adenosine receptor function; increased cortisol ...
It is also a potent catechol O-methyltransferase (COMT) inhibitor. 1,4-Dihydroxyanthraquinone (quinizarin) Alizarin, a related ...
March 2012). "Catechol-O-methyltransferase in complex with substituted 3'-deoxyribose bisubstrate inhibitors". Acta ... Manikumar G, Jin C, Rehder KS (2008). "Convenient Synthesis of Tolcapone, a Selective Catechol‐O‐methyltransferase Inhibitor". ... a novel inhibitor of catechol-O-methyltransferase". British Journal of Clinical Pharmacology. 48 (4): 513-20. 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. doi:10.1515/znc-1976-5-611 ... 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 ...
A comparison of dopamine agonists and catechol-O-methyltransferase inhibitors in Parkinson's disease. Clinical ...
It can inhibit 2-hydroxy and 4-hydroxyestradiol methylation by catechol-O-methyltransferase. It potently and specifically ...
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] ...
"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 ... "Entrez Gene: Leucine rich transmembrane and O-methyltransferase domain containing". Riahi Z, Bonnet C, Zainine R, Louha M, ...
"Genetic polymorphisms of catechol-O-methyltransferase modify the neurobehavioral effects of mercury in children". Journal of ...
In vitro, the meta-hydroxyl group of catechol is methylated by catechol-O-methyltransferase. Four of the five hydroxyl groups ...
"A catechol-O-methyltransferase that is essential for auditory function in mice and humans". Proceedings of the National Academy ...
Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M (August 1998). "Catechol-O-methyltransferase-deficient ...
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 ...
... 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 ...
However, the 4-hydroxy group makes it susceptible to metabolism by catechol-O-methyl transferase (COMT). Since it is β2- ...
Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE (August 2009). "Monoamine oxidase a and catechol-o-methyltransferase ...
"Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Alexithymia in Patients with Obsessive- ... levels associated with the Val/Val allele of the Rs4680 polymorphism in the gene that encodes Catechol-O-methyltransferase ( ...
"The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and ...
The catechol-o-methyl transferase gene (COMT) codes for an enzyme that degrades catecholamine neurotransmitters (DA and NE), ... Tunbridge, E. M. (9 June 2004). "Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates ...
... (metadrenaline) is a metabolite of epinephrine (adrenaline) created by action of catechol-O-methyl transferase on ...
An important gene for adolescent-onset schizophrenia is the catechol-O-methyltransferase gene, a gene that regulates dopamine. ...
... kanggo dieliminasi kanti pira-pira prosès kaya ta metilasi kanti enzim catechol-o-methyltransferase, hidroksilasi, oksidasi, ...
The meta-hydroxyl group of catechol is methylated by catechol-O-methyltransferase. Four of the five hydroxyl groups of ...
... allelic polymorphism of the catechol-O-methyltransferase (COMT) gene; increased adenosine receptor function; increased cortisol ...
... followed by methylation of the aromatic ring via catechol-O-methyl transferase. Then hydroxylation of both the aromatic ring ...
... of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase ( ...
Phenylethanolamine N-methyltransferase. catabolism:. *Catechol-O-methyl transferase. *Monoamine oxidase *A. *B ...
... this catechol group undergoes extensive metabolism upon uptake in the human body, for example by catechol-O-methyl transferase ... In many polyphenols the catechol group acts as an electron acceptor and is therefore responsible for the antioxidant activity.[ ...
Barnett, J. H.; Jones, P. B.; Robbins, T. W.; Müller, U. (27 February 2007). "Effects of the catechol-O-methyltransferase ... The low activity polymorphism of Catechol-O-methyltransferase is associated with slight increase in performance on executive ...
... catechol-o-methyl transferase, SK3 and opioid receptor delta-1.[44] Epigenetic modifications, such as DNA methylation, may ...
... which can be further modified by the enzyme phenylethanol N-methyltransferase to obtain epinephrine.[11] Since L-DOPA is the ... Phenylethanolamine N-methyltransferase. catabolism:. *Catechol-O-methyl transferase. *Monoamine oxidase *A. *B ...
... relating to transferase is the discovery of the mechanism of catecholamine breakdown by catechol-O-methyltransferase. This ... N-methyltransferase would be the standard naming convention for the transferase methylamine-glutamate N-methyltransferase, ... a DNA methyltransferase is a transferase that catalyzes the transfer of a methyl group to a DNA acceptor. In practice, many ... where methylamine is the donor, L-glutamate is the acceptor, and methyltransferase is the EC category grouping. This same ...
5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase. *Catechol-O-methyl transferase. Homocysteine. *Betaine ...
5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase. *Catechol-O-methyl transferase. Homocysteine. *Betaine ... Information about DNA methyltransferases and DNA methylation at epigeneticstation.com. *Data for a DNA methyltransferase (DNMT ... DNMT1 is the most abundant DNA methyltransferase in mammalian cells, and considered to be the key maintenance methyltransferase ... methyltransferases. Classification of all DNA methyltransferases". Gene. 157 (1-2): 3-11. doi:10.1016/0378-1119(94)00783-O. ...
... mandelic acid are formed as a result of metabolism of adrenaline and noradrenaline by monoamine oxidase and catechol-O-methyl transferase ...
In the cytosol, noradrenaline is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and ... water-soluble compounds that have a structure made of a catechol group and an amine group. The adrenal glands are responsible ...
Monoamine oxidase and catechol-O-methyl transferase activities in cat nictitating membrane and rat and guinea-pig vas deferens ...
... the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase ...
This has been postulated to be explained by variations of the gene which codes for the enzyme catechol-O-methyl transferase ( ...
"Association between the Catechol-O-Methyltransferase (COMT) Val¹⁵⁸Met Polymorphism and Alexithymia in Patients with Obsessive- ... levels associated with the Val/Val allele of the Rs4680 polymorphism in the gene that encodes Catechol-O-methyltransferase ( ...
Catechol-O-methyl transferase EC 2.1.1.6. *DNA methyltransferase EC 2.1.1.72, EC 2.1.1.113, EC 2.1.1.37 ...
... is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase ...
5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase. *Catechol-O-methyl transferase. Homocysteine. *Betaine ... Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the TPMT gene. ... methyltransferase activity. • thiopurine S-methyltransferase activity. • S-adenosyl-L-methionine binding. Cellular component. • ... evidence for catalysis by human liver thiol methyltransferase and thiopurine methyltransferase". J. Pharmacol. Exp. Ther. 266 ( ...
Histamine N-methyltransferase inhibitors. آمودیاکین • BW-۳۰۱U • دیفن هیدرامین • هارمالین • Metoprine • کیناکرین • SKF-۹۱٬۴۸۸ • ...
Catechol O-methyl transferase (COMT) inhibitors such as entacapone and tolcapone, which are used in the treatment of ... and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical ...
... can be directly metabolized by catechol-O-methyl transferase to 3-O-methyldopa, and then further to vanillactic acid. ...
The activity of tyrosinase is similar to catechol oxidase, a related class of copper oxidase. Tyrosinases and catechol oxidases ... regeneration of methionine: Methionine synthase/Homocysteine methyltransferase. *Betaine-homocysteine methyltransferase. * ... Tyrosinase carries out the oxidation of phenols such as tyrosine and dopamine using dioxygen (O2). In the presence of catechol ... benzoquinone is formed (see reaction below). Hydrogens removed from catechol combine with oxygen to form water. ...
Pooley, EC; Fineberg, N; Harrison, PJ (June 2007). "The met(158) allele of catechol-O-methyltransferase (COMT) is associated ... Azzam, A; Mathews, CA (15 November 2003). "Meta-analysis of the association between the catecholamine-O-methyl-transferase gene ...
... a major catecholamine metabolite that is produced by a consecutive action of monoamine oxidase and catechol-O-methyltransferase ...
... 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 ... 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, ...
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) ...
Purchase Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors, Volume 95 - 1st Edition ... Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors, Volume 95 1st Edition. 0.0 star ... Introductory remarks: Catechol-O-methyltransferase inhibition: an innovative approach to enhance L-dopa therapy in Parkinsons ... Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors ...
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 ...
Keywords: major depressive disorder, duloxetine, catechol-O-methyltransferase, 3-methoxy-4-hydroxyphenylglycol, homovanillic ... and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. Subjects and methods: Sixty-four patients and 30 ... Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3- ... Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3- ...
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 ...
A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the ... Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer Pharmacogenetics. 2001 Jun; ... A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the ...
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 ...
Green Tea Extract and Catechol-O-Methyltransferase Genotype Modify Fasting Serum Insulin and Plasma Adiponectin Concentrations ... stratified by catechol-O-methyltransferase (COMT) genotype. This study was conducted in a subset of 237 overweight and obese ...
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 (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common ... Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure ... Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure ... Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure ...
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 ...
These two catechol estrogens are converted to methylated metabolites by catechol-,i,O,/i,-methyltransferase (COMT). 4-OHE,sub,2 ... Inhibition of catechol-O-methyltransferase increases estrogen-DNA adduct formation ZAHID M ... 4-Hydroxyestradiol Induces γ-H2AX in the Presence of an Inhibitor of Catechol-O-methyltransferase in Human Breast Cancer MCF-7 ... Expression of cytochrome P450 1B1 and catechol-O-methyltransferase in breast tissue and their associations with breast cancer ...
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 ...
... metabolised by catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain whether the Val158Met catechol-O ... RESULTS: We did not find any significant association between the Val158Met catechol-O-methyltransferase gene polymorphism and ... More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in ... Hosák A, Serý M, Beranek A, Alda A, Lack of association between the Val158Met catechol-O-methyltransferase gene polymorphism ...
Generic options for Catechol-O-Methyltransferase Inhibitor pharmaceutical drugs, including patent status, patent expiration ... Catechol-O-Methyltransferase Inhibitor Drug Class List. ➠ Get the DrugPatentWatch Daily Briefing. » See Plans and Pricing ...
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 ...
Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis Res Ther 2007;9:R110. ... Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain 2006;125:216-24. ... Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int 2003;23:104-7. ... Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 2006; ...
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, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic ... Characterization and Implications of Estrogenic Down-Regulation of Human Catechol-O-Methyltransferase Gene Transcription Tao ... Characterization and Implications of Estrogenic Down-Regulation of Human Catechol-O-Methyltransferase Gene Transcription Tao ... Characterization and Implications of Estrogenic Down-Regulation of Human Catechol-O-Methyltransferase Gene Transcription Tao ...
Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity ... Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic ...
  • A functional single-nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyltransferase results in a valine to methionine mutation at position 158 (Val158Met) rs4680. (wikipedia.org)
  • Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine. (nih.gov)
  • The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) influences the enzyme activity. (nih.gov)
  • This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. (dovepress.com)
  • 1996). Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. (salimetrics.com)
  • Catechol-O-methyltransferase, which has a functional genetic polymorphism, plays an important role in dopamine metabolism. (ovid.com)
  • The study analyzed the association between the catechol-O-methyltransferase gene polymorphism and alcohol dependence in the Korean population. (ovid.com)
  • Polymerase chain reaction-based genotyping was used to verify the presence of the catechol-O-methyltransferase gene polymorphism. (ovid.com)
  • This suggests that the catechol-O-methyltransferase gene polymorphism is not associated with the development of alcohol dependence, but may affect the susceptibility to a clinical heterogeneity of alcohol dependence, at least in the Korean population. (ovid.com)
  • Lack of association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence. (nel.edu)
  • The main aim of the study was to ascertain whether the Val158Met catechol-O-methyltransferase gene polymorphism is associated with methamphetamine dependence in this Central European country. (nel.edu)
  • More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in individual clinical subtypes of dependence on methamphetamine involving e.g. psychotic features or violence. (nel.edu)
  • Hosák A, Serý M, Beranek A, Alda A, Lack of association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence. (nel.edu)
  • The effect of a non-synonymous single nucleotide polymorphism (SNP), rs4680 (V158M), in the gene coding for the enzyme catechol-O-methyltransferase (COMT) has been widely investigated in genetic association studies of chronic widespread pain (CWP). (bmj.com)
  • Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers. (biomedsearch.com)
  • Background: The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. (ebscohost.com)
  • No association between catechol-o-methyltransferase Val108/158Met polymorphism and schizophrenia or its clinical symptomatology in a Mexican population. (ebscohost.com)
  • Aims To study the possible association of catechol-O-methyltransferase ( COMT) Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to check whether the COMT Val/Val genotype is associated with MED12 exon 2 mutations in fibroids. (bmj.com)
  • The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been found to affect fear extinction and might play a role in the etiology of anxiety disorders. (lancs.ac.uk)
  • Modulation of brain structure by catechol-O-methyltransferase Val(158) Met polymorphism in chronic cannabis users. (nispa.nl)
  • Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. (nispa.nl)
  • 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. (ox.ac.uk)
  • 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. (ox.ac.uk)
  • A functional single nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyl transferase has been shown to affect cognitive tasks broadly related to executive function, such as set shifting, response inhibition, abstract thought, and the acquisition of rules or task structure. (chemeurope.com)
  • Most studies have focused on the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase. (umbrella-scientific.us)
  • Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val 158 Met polymorphism have been reported. (elsevier.com)
  • Association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder. (scienceopen.com)
  • Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer. (scienceopen.com)
  • Structural equation modeling was applied to data on 704 Norwegian children to test whether the catechol-O-methyltransferase Val158Met genotype moderates the effect of disorganized attachment, which was measured dimensionally at 4 years of age using the Manchester Child Attachment Story Task, on changes in aggressive behavior and social competence from ages 4 to 6. (samforsk.no)
  • The influence of Catechol-O-Methyltransferase Val158Met on fear of pain and placebo analgesia. (painresearchforum.org)
  • Fundist hefur breytileiki í einum basa (Val158Met, rs4680) í erfðaefninu á milli einstaklinga, sem veldur því að þegar A samsæta er til staðar er COMT ensímið mun lengur að brjóta niður dópamín en þegar G samsæta er til staðar7. (lsh.is)
  • We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol- O -methyltransferase ( COMT ) genotype in individual susceptibility to breast cancer. (aacrjournals.org)
  • A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the risk of breast cancer in Korean women. (nih.gov)
  • The Minnesota Green Tea Trial was a 12-mo randomized, double-blind, placebo-controlled clinical trial of 937 healthy postmenopausal women assigned to either decaffeinated GTE (1315 mg total catechins/d) or a placebo, stratified by catechol-O-methyltransferase (COMT) genotype. (nih.gov)
  • Despite the addition of a peripheral decarboxylase inhibitor, levodopa is extensively metabolised in the periphery to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). (bmj.com)
  • Identification of major metabolites of the catechol-O-methyltransferase inhibitor entacapone in rats and humans. (aspetjournals.org)
  • Metabolites of entacapone [(E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide++ +], a potent inhibitor of catechol-O-methyltransferase, were isolated from human and rat urine. (aspetjournals.org)
  • Karlsson M, Wikberg T (1992) Liquid chromatographic determination of a new catechol-O-methyltransferase inhibitor, entacapone, and its Z-isomer in human plasma and urine. (springer.com)
  • Entacapone is an inhibitor of catechol-O-methyltransferase (COMT), used in the treatment of Parkinson's disease as an adjunct to levodopa and carbidopa therapy. (rxlist.com)
  • Catechol O-methyltransferase inhibitor was associated with up to a 65% increase in JC410 cell number and a maximal 5.6-fold increase in p450SCC-luciferase activity at 20 μmol/L. Dihydrotestosterone, insulin, and ATRA all induced a dose-dependent increase in COMTP1-luciferase transactivation, as well as up-regulated COMT messenger RNA expression in granulosa cells. (elsevier.com)
  • Catechol O-methyltransferase product, 2-ME 2 , decreased, whereas COMT inhibitor increased granulosa cell proliferation and steroidogenesis. (elsevier.com)
  • Entacapone is a selective and reversible inhibitor of catechol- O -methyltransferase (COMT). (nih.gov)
  • Catechol-O-methyltransferase expression was measured in cells after treatment with tumor necrosis factor alpha (TNFα) alone or with lactacystin, a proteasome inhibitor. (elsevier.com)
  • Carbidopa, levodopa and entacapone tablets, a combination drug consisting of levodopa (aromatic amino acid), carbidopa (aromatic amino acid decarboxylation inhibitor), and entacapone (catechol-O-methyltransferase (COMT) inhibitor) is indicated for the treatment of Parkinson's disease. (nih.gov)
  • misc{d359f84f-dce1-45b6-b22f-f3eac7b75b3d, abstract = {A novel isolation procedure was developed that allowed the purification of rat liver and human placenta catechol-O-methyltransferase (EC 2.1.1.6, COMT) enzyme from rat and human sources to a degree sufficient to allow the amino acid sequencing of the enzyme. (lu.se)
  • Grünig, David;Felser, Andrea;Duthaler, Urs;Bouitbir, Jamal;Krähenbühl, Stephan 2018-04-23 00:00:00 Abstract Tolcapone and entacapone are catechol-O-methyltransferase inhibitors used in patients with Parkinson's disease. (deepdyve.com)
  • 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)
  • Our data suggest, that the CYP1B1 Ser allele may decrease endometrial cancer risk by altering the production of catechol estrogens. (cdc.gov)
  • The enzyme COMT is expressed in several tissues and degrades not only dopamine but also other catecholamines and sex steroids, like catechol estrogens and dietary polyphenols. (biomedcentral.com)
  • 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. (testcatalog.org)
  • Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol. (testcatalog.org)
  • OBJECTIVE: The catechol-O-methyltransferase enzyme catalyzes the methylation of the catechol estrogens, 2- or 4-hydroxyestrogen, to 2- or 4-methoxyestrogen. (elsevier.com)
  • Volume 95 of International Review of Neurobiology focuses on Catechol-O-methyltransferase inhibition, and its clinical application in relation to Parkinson's disease. (elsevier.com)
  • Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. (bmj.com)
  • The inhibition of soluble catechol- O -methyltransferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after single oral (5-800 mg) and IV (25 mg) doses have been examined in an open study in 12 healthy young male volunteers. (springer.com)
  • Keränen T, Gordin A, Harjola V-P, Karlsson M, Korpela K, Pentikäinen PJ, Rita H, Seppälä L, Wikberg T (1993) The effect of catechol-O-methyltransferase inhibition by entacapone, on the pharmacokinetics and metabolism of levodopa in healthy volunteers. (springer.com)
  • We investigated the effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non-toxic drug nitecapone on the metabolism of 6-[ 18 F]fluoro-l-dihydroxyphenylalanine (6FD) and on its positron emission tomography (PET) imaging in non-human primates. (elsevier.com)
  • Kopin, Irwin J. / 6-[18F]Fluoro-l-dihydroxyphenylalanine metabolism and positron emission tomography after catechol-O-methyltransferase inhibition in normal and hemiparkinsonian monkeys . (elsevier.com)
  • The nitro group of entacapone seems to hinder methylation of the catechol hydroxyls in man, because no methylation products were detected. (aspetjournals.org)
  • COMT inhibitors, HepaRG cells, fatty acid metabolism, long-chain acyl-CoA synthetase, VLDL secretion Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used for the treatment of patients with Parkinson's disease. (deepdyve.com)
  • Studies in healthy volunteers have shown that entacapone reversibly inhibits human erythrocyte catechol- O -methyltransferase (COMT) activity after oral administration. (nih.gov)
  • 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. (wikipedia.org)
  • Catechol- O -methyltransferase (COMT) metabolizes catecholamines ( Männisto and Kaakkola, 1999 ). (jneurosci.org)
  • Of particular interest was catechol-O-methyl transferase (COMT), an enzyme involved in metabolizing catecholamines released following neuronal activity. (pubmedcentralcanada.ca)
  • After validating altered expression of representative candidates by western blot analysis, we subsequently targeted catechol-O-methyl transferase (COMT), an enzyme involved in the metabolism of the catecholamines dopamine and norepinephrine, for a more extensive characterization. (pubmedcentralcanada.ca)
  • COMT degrades catecholamines, such as dopamine and epinephrine and catechol-containing drugs. (bmj.com)
  • Catechol- O -methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. (aspetjournals.org)
  • Given the previously established role of catecholamines in both placebo effects and stress, we hypothesized that genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, would moderate responses to an intervention intended to alter participants' mindsets about stress. (columbia.edu)
  • The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. (ebscohost.com)
  • Catechol-O-Methyltransferase (COMT) is an enzyme that inactivates catecholamines, such as epinephrine, norepinephrine and dopamine. (genelex.com)
  • Catechol-O-methyltransferase (COMT) has two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-MT), anchored to intracellular membranes. (helsinki.fi)
  • Other tissues, including the liver, kidneys, and blood, produce a shorter form of the enzyme called soluble catechol-O-methyltransferase (S-COMT). (umbrella-scientific.us)
  • The rat and human recombinant soluble and membrane-bound catechol O-methyltransferase (S- and MB-COMT, respectively) were expressed using mammalian and baculovirus vectors. (lu.se)
  • Generation of membrane-bound catechol-O-methyl transferase deficient mice with disctinct sex dependent behavioral phenotype. (helsinki.fi)
  • Specifically, membrane-bound catechol- O -methyltransferase (MBCOMT) is an integral membrane protein that catalyzes the methylation of catechol substrates and has been linked to several diseases such as Parkinson's disease and Schizophrenia. (biomedcentral.com)
  • The longer form, called membrane-bound catechol-O-methyltransferase (MB-COMT), is chiefly produced by nerve cells in the brain. (umbrella-scientific.us)
  • Catechol-O-methyltransferase (COMT) plays an important role in normal brain function and has been implicated in human disorders, such as Parkinson's disease. (bertin-bioreagent.com)
  • Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids, are substrates of COMT. (wikipedia.org)
  • Using S-adenosyl-L-methionine (SAM) as a methyl donor, COMT methylates catechol substrates, w. (bertin-bioreagent.com)
  • COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. (nih.gov)
  • Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. (wikipedia.org)
  • Methyltransferases can also be grouped as different types utilizing different substrates in methyl transfer reactions. (wikipedia.org)
  • Lysine methyltransferases and Arginine methyltransferases are unique classes of enzymes, but both bind SAM as a methyl donor for their histone substrates. (wikipedia.org)
  • Catechol-O-methyltransferase (COMT) inactivates norepinephrine and dopamine via methyl conjugation, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity. (elsevier.com)
  • In particular, catechol-O-methyltransferase (COMT) plays a critical role in determining the fraction of MDMA that is converted to potentially neurotoxic metabolites. (elsevier.com)
  • Methylation of these catechols by COMT limits their oxidation and conjugation to glutathione, a process that ultimately gives rise to neurotoxic metabolites. (elsevier.com)
  • The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. (nih.gov)
  • Because catechol-O-methyltransferase activity controls levels of these metabolites, it may help regulate the cellular estrogenic milieu. (elsevier.com)
  • Natural product methyltransferases provide a variety of inputs into metabolic pathways, including the availability of cofactors, signalling molecules, and metabolites. (wikipedia.org)
  • Catechol-o-methyltransferase (COMT) is important for modulating dopamine levels, prefrontal cortex (PFC) function, and several psychiatric phenotypes. (ox.ac.uk)
  • 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. (elsevier.com)
  • Catechol-O-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). (wikipedia.org)
  • Catechol-O-methyltransferase (COMT) is a catabolic enzyme involved in the degradation of bioactive molecules including the neurotransmitters epinephrine , norepinephrine , and dopamine . (bvsalud.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)
  • Although the aetiology of aggression is multifactorial, three studies have reported associations between polymorphisms of the catechol-O-methyltransferase (COMT) gene and aggression in schizophrenia. (elsevier.com)
  • COMT (catechol-O-methyltransferase) is an enzyme which inactivates catechols, including the significant neurotransmitters dopamine, noradrenaline and adrenaline [ 9 ]. (medsci.org)
  • Catechol-O-methyltransferase (COMT) polymorphisms predict treatment response in electroconvulsive therapy. (ebscohost.com)
  • In humans, catechol-O-methyltransferase protein is encoded by the COMT gene. (wikipedia.org)
  • 2004). Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme Activity in Postmortem Human Brain. (salimetrics.com)
  • Catechol-o-methyltransferase enzyme activity and protein expression in human prefrontal cortex across the postnatal lifespan. (ox.ac.uk)
  • COMTD1 (Catechol-O-Methyltransferase Domain Containing 1) is a Protein Coding gene. (genecards.org)
  • These types include protein methyltransferases, DNA/RNA methyltransferases, natural product methyltransferases, and non-SAM dependent methyltransferases. (wikipedia.org)
  • NF-κB (a protein involved in inflammation) is a known methylation target of the methyltransferase SETD6, which turns off NF-κB signaling by inhibiting of one of its subunits, RelA. (wikipedia.org)
  • Objective: To investigate the regulation of catechol O-methyltransferase (COMT) expression in granulosa cells and assess potential effects of 2-methoxyestradiol (2-ME 2 ) and COMT inhibitors on granulosa cell steroidogenesis and proliferation. (elsevier.com)
  • A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain. (medlineplus.gov)
  • Histone methyltransferases are critical for genetic regulation at the epigenetic level. (wikipedia.org)
  • Structural mechanism of S-adenosyl methionine binding to catechol O-methyltransferase. (nih.gov)
  • Methyltransferases possess a homologous domain that requires both a divalent metal cation and S-adenosyl-L-methionine (SAM) to catalyze its reactions. (nih.gov)
  • Catechol-O-methyltransferase (COMT) plays an essential role in detoxification of catechols by transferring the methyl group from S-adenosyl-L-methionine to the substrate. (muni.cz)
  • The most common class of methyltransferases is class I, all of which contain a Rossmann fold for binding S-Adenosyl methionine (SAM). (wikipedia.org)
  • Catechol-O-methyltransferase (COMT Val 158 Met) has been implicated in both depression and cardiovascular disease. (biomedcentral.com)
  • Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. (hmdb.ca)
  • In this study, we characterized the enzymology of cytosolic catechol- O -methyltransferase (COMT)-catalyzed methylation of EGCG and EGC in humans, mice, and rats. (aspetjournals.org)
  • Catechol-O-methyltransferase (COMT) catabolises dopamine and is important for regulating dopamine levels in the prefrontal cortex. (scienceopen.com)
  • Expression of multiple catechol-o-methyltransferase (COMT) mRNA variants in human brain. (ox.ac.uk)
  • Many clinical and genomic association studies suggested that the catechol-Omethyltransferase (COMT) gene region was an important genetic locus for psychiatric disorders, because of the proposed relationship between its function in catecholaminergic neurotransmission and individual response to antidepressants, and vulnerability to psychiatric disorders. (eurekaselect.com)
  • Epistatic and functional interactions of catechol-o-methyltransferase (COMT) and AKT1 on neuregulin1-ErbB signaling in cell models. (ox.ac.uk)
  • We investigated whether functional polymorphisms in catechol-O-methyltransferase (COMT) influence tHcy, since COMT activity produces S-adenosylhomocysteine (SAH), a homocysteine precursor. (ox.ac.uk)
  • In the brain, catechol-O-methyltransferase helps break down chemical messengers called neurotransmitters which are responsible for conducting signals from one nerve cell to another. (umbrella-scientific.us)
  • Catechol-O-methyltransferase helps maintain appropriate levels of these neurotransmitters in this part of the brain. (umbrella-scientific.us)
  • The change affects the stability and activity of catechol-O-methyltransferase, which alters the enzyme's ability to break down neurotransmitters in the prefrontal cortex. (umbrella-scientific.us)
  • In the brain, catechol-O-methyltransferase helps break down certain chemical messengers called neurotransmitters. (medlineplus.gov)
  • Association between catechol-O-methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case-control study. (painresearchforum.org)
  • Catechol- O -methyl transferase (COMT) ( EC 2.1.1.6) is an enzyme first discovered by biochemist Julius Axelrod. (chemeurope.com)
  • 2005). Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations. (salimetrics.com)
  • This review summarizes the major classes of COMT inhibitors, from early catechol and pyrogallol variants to bisubstrate inhibitors. (eurekaselect.com)
  • Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. (uio.no)
  • GTE contains catechins, which inhibit the enzyme catechol O -methyltransferase and thereby stimulate SNS. (nature.com)
  • COMT (Catechol-O-methyltransferase) inhibitors enhances levodopa treatment as they inhibit levodopa's peripheral metabolism, thereby enhancing its bioavailability. (holisticonline.com)
  • Since the identification of Catechol-O-Methyltransferase (COMT) by Axelrod in 1957, many inhibitors of this enzyme have been reported. (eurekaselect.com)
  • Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway that result in the hydroxylation and conjugation of estradiol, respectively. (cdc.gov)
  • Neslihan Aygun Kocabas, "Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major Depressive Disorder (MDD)", CNS & Neurological Disorders - Drug Targets (2012) 11: 264. (eurekaselect.com)
  • RATIONALE: Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, which is important in mediating drug reward such as nicotine in tobacco smoke. (biomedsearch.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)
  • Impact of physical exercise on catechol-O-methyltransferase activity in depressive patients: A preliminary communication. (bvsalud.org)
  • Gene Ontology (GO) annotations related to this gene include O-methyltransferase activity . (genecards.org)
  • Little is known, however, about the relationship between catechol-O-methyltransferase activity and the specific mental and emotional problems characteristic of this condition. (medlineplus.gov)
  • Kaakkola S, Wurtman R (1993) Effects of catechol-O-methyltransferase inhibitors and 1-3, 4-dihydroxyphenylalanine with or without carbidopa on extracellular dopamine in rat striatum. (springer.com)
  • Guldberg HC, Marsden CA (1975) Catechol-O-methyltransferase: Pharmacological aspects and physiological role. (springer.com)
  • Catechol- O -methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. (sciencemag.org)