Activation and Inhibition of Adrenaline Metabolism

Axelrod, Julius; Tomchick, Robert

doi:10.1038/1842027a0

Cited by 80 publications

(57 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…+ OH-+ 02. These reactive species may contribute significantly to the noncompetitive effects of pyrogallol on catechol 0-methyltransferase, which contains an "essential" sulfhydryl group [30]. It can also be questioned whether the competitive part of the inhibition is due to the pyrogallol or to its oxidation products.…”

Section: Effects Of Pyrogallol On Catechol 0-methyltransferasementioning

confidence: 99%

Involvement of the Superoxide Anion Radical in the Autoxidation of Pyrogallol and a Convenient Assay for Superoxide Dismutase

Marklund

1974

European Journal of Biochemistry

8,733

3,865

View full text Add to dashboard Cite

The autoxidation of pyrogallol was investigated in the presence ofEDTA in the pH range7.9-10.6. The rate of autoxidation increases with increasing pH. At pH 7.9 the reaction is inhibited to 99 by superoxide dismutase, indicating an almost total dependence on the participation of the superoxide anion radical, 02.-, in the reaction. Up to pH 9.1 the reaction is still inhibited to over 90% by superoxide dismutase, but at higher alkalinity, O,.--independent mechanisms rapidly become dominant.Catalase has no effect on the autoxidation but decreases the oxygen consumption by half, showing that H202 is the stable product of oxygen and that H20, is not involved in the autoxidation mechanism.A simple and rapid method for the assay of superoxide dismutase is described, based on the ability of the enzyme to inhibit the autoxidation of pyrogallol.A plausible explanation is given for the non-competitive part of the inhibition of catechol 0-methyltransferase brought about by pyrogallol.Pyrogallol (1,2,3-benzenetriol) has long been known to autoxidize rapidly, especially in alkaline solution and the reaction has been employed for the removal of oxygen from gases.Molecular oxygen, carrying two unpaired electrons with parallel spins, has a preference for univalent reduction because spin restrictions arise when reduction with electron pairs is attempted [l]. The recently discovered enzyme superoxide dismutase [2] extremely rapidly dismutases univalently reduced oxygen 02.-, the superoxide anion radical (2 02.-+ 2 H + -+ 0, no saturation kinetics at the O,.-concentrations which have been feasible to produce [7] and hence induces a pseudo-first order dismutation of O,.-.The present paper describes studies of the autoxidation of pyrogallol under various conditions. The role of 02.-in the reactions was investigated with the aid of superoxide dismutase. The data obtained allotted suitable conditions for a convenient assay of superoxide dismutase. MATERIALS AND METHODS+ H,O,). The enzyme has proven to be a useful probe for studying the participation of the radical in reac-

show abstract

Section: Effects Of Pyrogallol On Catechol 0-methyltransferasementioning

confidence: 99%

Involvement of the Superoxide Anion Radical in the Autoxidation of Pyrogallol and a Convenient Assay for Superoxide Dismutase

Marklund

1974

European Journal of Biochemistry

8,733

3,865

View full text Add to dashboard Cite

show abstract

“…Catechol-O-methyltransferase (COMT; EC 2.1.1.6) catalyzes transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to the hydroxyl group of a variety of catechols, including catecholamine neurotransmitters and the catechol estrogens (23)(24)(25). There are two major COMT isoforms in humans, the soluble cytosolic form (S-COMT) and the membrane-bound endoplasmic reticulum form (MB-COMT) encoded by a single gene at 22q11.2 (26,27).…”

mentioning

confidence: 99%

Detoxication of Structurally Diverse Polycyclic Aromatic Hydrocarbon (PAH) o-Quinones by Human Recombinant Catechol-O-methyltransferase (COMT) via O-Methylation of PAH Catechols

Zhang

Jin

Chen

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Polycyclic aromatic hydrocarbons (PAH)2 are ubiquitous environmental pollutants that are products of fossil fuel combustion and found in tobacco smoke and are suspect lung carcinogens (1, 2). PAH are considered to be procarcinogens and require metabolic activation to elicit their deleterious effects. Benzo[a]pyrene (B[a]P) is a representative PAH and widely used to study the metabolic activation of PAH (3, 4).There are three major pathways for the activation of B[a]P. In the first pathway, P450 peroxidases catalyze the generation of radical cations (5) PAH o-quinones, produced by AKRs are electrophilic and highly reactive to endogenous nucleophiles. PAH o-quinones can readily form conjugates with cellular thiols to yield and GSH conjugates, leading to their elimination (12,13). PAH o-quinones can also react with DNA to form both stable and depurinating adducts, which may result in mutagenesis (14 -16). PAH o-quinones are also able to undergo nonenzymatic/enzymatic reduction to reform catechols at the expense of NADPH and establish futile redox cycles that amplify the generation of reactive oxygen species (ROS). ROS can cause DNA damage resulting in the formation of 7,8-dihydro-8-oxo-2Ј-deoxyguanosine (8-oxo-dGuo) lesions and can contribute to G to T transversions in ras and p53 (17,18). PAH o-quinones were found to be more mutagenic than diol-epoxides in an in vitro p53 mutagenesis assay provided they redox-cycled and a linear correlation was observed

show abstract

“…A more recent follow-up study (11) on behavioral phenotypes observed in patients with the 22q11 deletion reported OC symptoms in the majority of these patients, thus providing even stronger evidence that the 22q11 locus harbors gene(s) predisposing to OCD. The gene for catechol-O-methyltransferase (COMT) (12,13), which is involved in the inactivation of catecholamines including the neurotransmitter dopamine (14), maps to the 22q11 region (15), and is frequently deleted in patients with 22q11 microdeletions (9). comt therefore represents an attractive candidate gene for OCD.…”

mentioning

confidence: 99%

Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Karayiorgou

Altemus

Galke

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

288

182

View full text Add to dashboard Cite

In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD). We show that a common functional allele of this gene, which results in a 3-to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males. This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene. The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point.

show abstract

Activation and Inhibition of Adrenaline Metabolism

Cited by 80 publications

References 4 publications

Involvement of the Superoxide Anion Radical in the Autoxidation of Pyrogallol and a Convenient Assay for Superoxide Dismutase

Involvement of the Superoxide Anion Radical in the Autoxidation of Pyrogallol and a Convenient Assay for Superoxide Dismutase

Detoxication of Structurally Diverse Polycyclic Aromatic Hydrocarbon (PAH) o-Quinones by Human Recombinant Catechol-O-methyltransferase (COMT) via O-Methylation of PAH Catechols

Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Contact Info

Product

Resources

About