Oxidative Inhibition of Human Soluble Catechol-O-methyltransferase

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Oxidative inhibition of human soluble catechol-O-methyltransferase.

A common polymorphism in the human gene for catechol-O-methyltransferase results in replacement of Val-108 by Met in the soluble form of the protein (s-COMT) and has been linked to breast cancer and neuropsychiatric disorders. The 108M and 108V variants are reported to differ in their thermal stability, with 108M COMT losing catalytic activity more rapidly. Because human s-COMT contains seven c...

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Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase.

Molecular mechanisms determining the turn-over rate and specificity of catechol O-methylation were studied by combining enzyme kinetic measurements, computational modeling of substrate properties and fitting ligands in a 3D model of the active site of the enzyme. Enzyme kinetic measurements were carried out for 46 compounds, including most clinically used catechol drugs, by using recombinant hu...

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Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT) receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT), an enzyme that contributes to modultion the ...

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Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase

BACKGROUND Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Specifically, low COMT activity is associated with heightened pain perception and development of musculoskeletal pain in humans as well as increased experimental pain sensitivity in rodents. RESULTS We report that the proinflammatory cytokine tumor...

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Inhibition of catechol-O-methyltransferase by hydroxybenzenes and related compounds.

The inhibitory action of 1, 2, 3-trihydroxybenzene (pyrogallol) on the activity of catechol-O-methyltransferase (COMT) is well known (1-4). Recently, 1, 3, 5,-trihydroxy benezene (phloroglucinol) and 2, 4, 6-trihydroxy-l-propiophenom~ (THPP) have been shown to exert spasmolytic action in experimental animals and to relieve spastic disorders of the urinary tract and biliary ducts in patients (5-...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2004

ISSN: 0021-9258

DOI: 10.1074/jbc.m401086200