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Enzymatic O-Methylation of Epinephrine and Other Catechols
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“The O-methylation of catechols plays an important role in the phase 2 metabolism of estrogens (Section 4.4.1) and is catalyzed by the enzyme catechol-O-methyltransferase (COMT) [179]”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [179]
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“In the presence of AdoMet and magnesium, COMT inactivates biologically active catechols through O-methylation [33].”
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“Catechol O-methyltransferase (COMT) is an S-Adenosyl-L-methionine (SAM)- and Mg-dependent methyltransferase (MTase)[9] that reacts with an array of catecholamine substrates (e.”
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“In particular, dopa and dopamine methylations control the levels of these signaling molecules and are important in neurochemistry (3, 6).”
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“COMT catalyzes the transfer of the methyl group from SAM to the meta-hydroxyl group of phenolic compounds with a catechol structure (Axelrod and Tomchick, 1958).”
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“Axelrod and Tomchick first described and characterized catechol-O-methyltransferase (COMT) in the cytosolic fraction of liver and other organs as the enzyme responsible for catalyzing the O-methylation of catecholamine neurotransmitters [1].”
BackgroundZhu, B. T., Patel, U. K., Cai, M. X., Lee, A. J., & Conney, A. H. (2001) · Xenobiotica · doi:10.1080/00498250110079798 · Cited by 45
“…(COMT), an enzyme ubiquitously present in high activity in rodents and humans, catalyses the metabolic O-methylation of endogenous catecholamines and catechol oestrogens (Axelrod and Tomchick 1958, Axelrod 1966, Guldberg and Marsden 1975, Thakker and Creveling 1990, Zhu and Conney 1998).”
BackgroundViolence in Male Patients with Schizophrenia: Risk Markers in a South African Population
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“Consequently, as catechol-O-methyltransferase (COMT) is known to be pivotal to biogenic amine metabolism (serotonin and dopamine) [17], this enzyme has been regarded as a possible factor in regulating violent behaviour.”
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“…with the findings from the in vitro enzyme inhibition experiment, these results further confirmed that COMT catalyzes the transfer of methyl group from SAM to the meta-hydroxyl group of SAA, which is the same for other phenolic compounds with a catechol structure (Axelrod and Tomchick, 1958).”
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Differences in the uptake, storage and metabolism of (+)‐ and (—)‐noradrenaline
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“Methylation is involved in various biosynthetic pathways (e.g., phenylpropanoid metabolism of plants), in the inactivation of active molecules such as the neurotransmitters adrenaline and noradrenaline (Axelrod and Tomchick 1958; Rivett et al. 1982), and in other regulatory processes.”
BackgroundCell‐free synthesis of rat and human catechol O‐methyltransferase
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“…an enzyme almost ubiquitously present in all tissues, catalyses the metabolic O-methylation of a wide variety of endogenous and exogenous catechol-containing substrates using S-adenosyl-L-methionine (AdoMet) as the methyl donor (Axelrod & Tomchick 1958; Axelrod 1966; Zhu et al. 2000; Zhu 2002).”
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Structural Mechanism of S-Adenosyl Methionine Binding to Catechol O-Methyltransferase
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BackgroundEnzymatic synthesis ofS-adenosyl-l-methionine froml-methionine and ATP
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BackgroundThe nutritional incidence of flavonoids: some physiological and metabolic considerations
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“It appears likely that the increase in methylated amine formation from D,L-[3H]NE reflects the preference of monoamine oxidase for the naturally occurring L-isomer (26, 27) since catechol-O-methyltransferase does not display stereospecificity (26, 28).”
BackgroundThe Metabolism of Sympathomimetic Bronchodilator Drugs by the Isolated Perfused Dog Lung
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Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice
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“The COMT enzyme catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to one of the hydroxyls on a catechol structure (Axelrod & Tomchick 1958) leading to catecholamine inactivation.”
BackgroundCatechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response
Ji, Y., Biernacka, J. M., Snyder, K., Drews, M., Pelleymounter, L. L., Colby, C., Wang, L., Mrazek, D. A., & Weinshilboum, R. M. (2010) · The Pharmacogenomics Journal · doi:10.1038/tpj.2010.69 · Cited by 40
Strous, R. D., Lapidus, R., Viglin, D., Kotler, M., & Lachman, H. M. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.09.067 · Cited by 37
Stability of human plasma catecholamines
Pettersson, J., Hussi, E., & Jaänne, J. (1980) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365518009092647 · Cited by 37
Studies on the Metabolism of Catecholamines
Axelrod, J., WHITBY, I. G., Hertting, G., & KOPIN, I. L. (1961) · Circulation Research · doi:10.1161/01.res.9.3.715 · Cited by 37
Persson, K. Ö. U., & Persson, K. (1972) · Xenobiotica · doi:10.3109/00498257209111064 · Cited by 37
The β-adrenoceptors of the lung mediating inhibition of antigen-induced histamine release
Sörenby, L. (1975) · European Journal of Pharmacology · doi:10.1016/0014-2999(75)90092-8 · Cited by 37
Kopin, I. J., & Weise, V. K. (1968) · Biochemical Pharmacology · doi:10.1016/0006-2952(68)90083-x · Cited by 37
Metadata
- Authors
- Axelrod, J., & Tomchick, R.
- Affiliations
- United States Public Health Service (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1958-09
- Volume
- 233
- Issue
- 3
- Pages
- 702-705
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1543624067
- Cited by
- 1,283
- References
- 16
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 12 · 2022: 14 · 2021: 19 · 2020: 11 · 2019: 16 · 2018: 13 · 2017: 15 · 2016: 28 · 2015: 12 · 2014: 14 · 2013: 19 · 2012: 21
- FWCI
- 55.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Keywords
- epinephrine, catechol, O-methylation, enzymatic methylation, catecholamine metabolism
- MeSH terms
- Catechols, Epinephrine, Methylation, Norepinephrine, Transferases
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