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Showing papers on "Catechol-O-methyl transferase published in 1981"


Journal ArticleDOI
TL;DR: The localization of COMT in the leptomeninges, choroid plexus, and ciliary epithelium is consistent with a role for this enzyme in the separation of catechol compounds synthesized in the central nervous system, from those of peripheral origin.

52 citations


Journal ArticleDOI
TL;DR: The results are compatible with the conclusion that the genetic polymorphism which regulates RBC COMT activity may also regulate the level of human lymphocyte COMTActivity.
Abstract: Human erythrocyte (RBC) catechol-O-methyltransferase (COMT) is under genetic control. Experiments were performed to determine whether COMT in the human lymphocyte is regulated in parallel with RBC COMT. Supernatants of lymphocyte homogenates contained COMT activity. However, they also contained a potent COMT inhibitor, the effect of which could be negated by dilution. Lymphocyte COMT activity was maximal at a reaction pH of 7.7 an at a MgCl2 concentration of 0.67 mM. The apparent Km value for 3,4-dihydroxybenzoic acid, the catechol substrate for the reaction, was 1.2 x 10(-5) M and that for S-adenosyl-L-methionine, the methyl donor, was 2.3 x 10(-6) M. An average of 48.3 /+- 3.3% (mean /+- SEM) of the enzyme activity in crude lymphocyte homogenates from 3 subjects was removed by centrifugation at 100,000 g for 1 hr and was presumed to be membrane associated. The average COMT activity in lymphocytes isolated from blood of 23 randomly selected adult subjects was 14.0 /+- 1.2 units/10(6) cells (mean /+- SEM) or 913 /+- 69 units/mg protein. There was a significant correlation of relative RBC with relative lymphocyte COMT activity in these 23 subjects. The correlation coefficient was 0.733 (P less than 0.001) when lymphocyte enzyme activity was expressed per milligram of protein and 0.649 (P less than 0.001) when lymphocyte activity was expressed per 10(6) cells. These results are compatible with the conclusion that the genetic polymorphism which regulates RBC COMT activity may also regulate the level of human lymphocyte COMT activity.

39 citations


Journal ArticleDOI
TL;DR: It is suggested that a genetically determined deficiency of catecholamine degradative enzymes in the central nervous system or influences of nongenetic hormonal factors could be implicated in the findings of altered erythrocyte COMT activity reported.
Abstract: A significant decrease in catechol-O-methyltransferase (COMT) activity of erythrocytes was found in both male and female schizophrenic patients, as well as in male patients with schizophreniform psychosis. Among control subjects, a sex difference in COMT activity of erythrocytes was found, with males showing significantly higher activity than females. It is suggested that a genetically determined deficiency of catecholamine degradative enzymes in the central nervous system or, alternatively, influences of nongenetic hormonal factors could be implicated in the findings of altered erythrocyte COMT activity reported.

32 citations


Journal ArticleDOI
TL;DR: This assay led to the discovery of a dialyzable factor in the plasma of chronic uraemic patients which inhibits catechol-O-methyltransferase activity in vitro and its implication in physiopathological disorders remain to be established.

30 citations


Journal Article
TL;DR: Catechol-O-methyltransferase with S-adenosylmethionine as the methyl donor catalyzes preferentially p- O-methylation when 5-fluorodopa is the substrate, and results are a consequence of fluorine-induced ionization at the p-hydroxyl group.
Abstract: Catechol-O-methyltransferase (COMT, EC 2.1.1.6) with S-adenosylmethionine as the methyl donor catalyzes preferentially p-O-methylation when 5-fluorodopa is the substrate. The rate of this reaction is characterized by a Km of 0.4 ± 0.2 mmole/liter and a Vmax of 27 ± 11 mmoles/mg of COMT per minute at pH 7.9. We conclude that these results are a consequence of fluorine-induced ionization at the p-hydroxyl group.

22 citations


Journal ArticleDOI
TL;DR: It is concluded that inherited variation in activity of these two catabolic enzymes is not sufficient to explain alterations in monoamine metabolism described in dystonia, an inherited movement disorder of unknown etiology.
Abstract: Fibroblasts provide a source of living cells that can be obtained easily from humans and used to evaluate inherited differences in the activities of enzymes important in neurotransmitter and drug metabolism. Here, we describe biochemical characteristics of catechol-O-methyltransferase (COMT, EC 2.1.1.6) activity in homogenates of cultured human skin fibroblasts. Many properties of the enzyme, including apparent affinity for dihydroxybenzoic acid and S-adenosyl methionine, optimal pH and (Mg++), and inhibition by Ca++, are similar to those reported in lysates of human erythrocytes. Culture and assay conditions have been established for optimal and reproducible measurement of COMT activity in individual fibroblast lines. In 16 control lines, COMT activity ranged from 115 to 263 pmol/min/mg protein with a mean of 181 pmol/min/mg protein. Enzyme activity did not vary with the age or sex of the donor. The COMT activities in fibroblasts from eight patients with dystonia musculorum deformans, an inherited movement disorder of unknown etiology, were not significantly different from controls. Monoamine oxidase (MAO, EC 1.4.3.4) type A activity was measured in 12 lines from patients with dystonia, and values did not differ significantly from age- and sex-matched controls. We conclude that inherited variation in activity of these two catabolic enzymes is not sufficient to explain alterations in monoamine metabolism described in this disorder.

14 citations


Book ChapterDOI
01 Jan 1981
TL;DR: The extraneuronal inactivation of catecholamines and the detoxification of many xenobiotic catechols are dependent upon the enzyme catecholl-O-methyltransferase (COMT), a soluble, magnesium-requiring enzyme which catalyzes the transfer of a methyl group from S-adenosylmethionine to a catechobiotic substrate resulting in the formation of the meta and para- O-methylated products.
Abstract: The extraneuronal inactivation of catecholamines and the detoxification of many xenobiotic catechols are dependent upon the enzyme catechol-O-methyltransferase (COMT, EC 2.1.1.6). COMT is a soluble, magnesium-requiring enzyme which catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to a catechol substrate resulting in the formation of the meta and para-O-methylated products (Borchardt, 1980).

2 citations


Book ChapterDOI
01 Jan 1981
TL;DR: The effects of U-0521, a COMT inhibitor, on both COMT activity and the bioavailability of DOPA and dopamine (DA) in the rat corpus striatum was studied.
Abstract: We studied the effects of U-0521, a COMT inhibitor, on both COMT activity and the bioavailability of DOPA and dopamine (DA) in the rat corpus striatum. The COMT assay of Quiran and Weinshilboum (1975) required modification because of the presence of U-0521, and we used dopamine as the the methyl group acceptor. The reaction products, 3-O-(14C)-methyl-dopamine and O-(14C)-methyl-U-0521 were separated on cation exchange resin. Rats were injected i.p. with U-0521 (200 mg kg−1) and sacrificed at 0–120 min. Maximal in vivo inhibition (94%) was obtained at 5’ with enzyme recovery to 64% of basal activity at 120’. Rats were injected i.p. with U-0521 (0–250 mg kg−1) and sacrificed at 10’. Maximal inhibition (85%) was obtained at 200 mg kg−1 with an IC50 of 78 mg kg−1. Rats were injected i.p. with U-0521 (150 mg kg−1) and 10’ later with L-DOPA (100 mg kg−1). Control animals were injected with L-DOPA alone. DOPA, DA, HVA and DOPAC were assayed at 0–120’ in striatal homogenates using HPLC. L-DOPA peak at 15’ was significantly higher in U-0521 pretreated rats compared with control rats (3.0 ± 0.3 vs. 1.09 ± 0.1, p0.005 on two-tailed student t-test). All results are expressed as ng/mg tissue weight ± SEM (n=4).

Book ChapterDOI
01 Jan 1981
TL;DR: The presence of COMT in ventricular ependyma suggests a restriction of free diffusion between CSF and brain parenchyma with the exception of specific areas where ependYma lacks the enzyme.
Abstract: Catechol-O-methyltransferase (COMT) has been localized to the non-neuronal elements of the central nervous systems. Its localization to pia-arachnoid and choroid plexuses imply an enzymatic barrier to prevent catechols of peripheral origin from entering the brain or CSF. The presence of COMT in ventricular ependyma suggests a restriction of free diffusion between CSF and brain parenchyma with the exception of specific areas where ependyma lacks the enzyme. Perineuronal oligodendrocytes adjacent to some cortical neurons contain COMT. The processes from these cells may protect specific catechol synapses from the more general effects of catecholamines acting by a neurohumeral mechanism.