Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We modified the single-isotope radioenzymatic assay for catecholamines [Life Sci. 21, 625 (1977)] to assay 3, 4-dihydroxyphenylalanine (DOPA). DOPA decarboxylase is used to convert DOPA to dopamine, which concurrently is converted to [3H]-3-O-methyldopamine in the presence of catechol-O-methyltransferase and [methyl-3H]-S-adenosylmethionine and assayed radioenzymatically. For assay of plasma DOPA, 50 microliter of untreated plasma is added directly into the incubation mixture. A duplicate mixture containing an internal standard requires a second 50-microliter aliquot of plasma. Because the assay measures both DOPA and endogenous dopamine, two additonal aliquots of plasma must be assayed for dopamine in the absence of the decarboxylase by the differential assay; DOPA is estimated by difference. The assay is sensitive to 25 pg (500 ng/liter of plasma). Analysis of DOPA (DOPA plus dopamine) and the concurrent differential assay of catecholamines in at least 10 samples can be done in a single working day. Plasma DOPA concentrations for 42 normotensive adults were 1430 +/- 19 ng/liter (mean +/- SEM). In contrast, do-pamine concentrations for these same subjects averaged 23 +/- 20 ng/liter. Values for the 24 women subjects (15 10 +/- 62 ng/liter) significantly (P = 0.04) exceeded those for the men (1320 +/- 75 ng/liter).
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PMID:Radioenzymatic assay of DOPA (3,4-dihydroxyphenylalanine). 70 23

The purpose of this study was to determine if there is a difference in the biochemical composition of the edge of a tumor and the center of a tumor. There was a greater concentration of histamine in the edge (mean +/- SEM, 9.3 +/- 1.2 pmole/mg of wet weight) than in the center (3.6 +/- 0.4 pmole/mg of wet weight) of a transplantable golden hamster insulinoma. There was, however, no difference in the concentration of norepinephrine, protein, DNA, or phosphate, or in the activity of the enzymes, monoamine oxidase, catechol-O-methyltransferase, L-dopa decarboxylase, or 5'-nucleotidase in the edge or in the center of the tumor. Using chemical analysis and autoradiography, there was a comparable incorporation of tritiated thymidine in the edge and in the center of the tumor.
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PMID:Biochemical composition of edge and center of malignant hamster insulinoma. 609 91

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.
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PMID:Catechol-o-methyltransferase biochemical genetics: human lymphocyte enzyme. 733 86

Thiopurine methyltransferase (TPMT) catalyzes thiopurine S-methylation, an important metabolic pathway for drugs such as 6-mercaptopurine. Thiol methyltranferase (TMT) catalyzes the S-methylation of a variety of aliphatic sulfhydryl compounds. Erythrocyte (RBC) TPMT activity is elevated in the blood of uremic patients on maintenance hemodialysis, 15.83 +/- 0.90 U/ml RBCs (mean +/- SEM, n = 41), whereas in blood from randomly seleted nonuremic subjects it was 12.76 +/- 0.16 U/ml (n = 298, p < 0.001). RBC TPMT activity is not affected by hemodialysis. The plasma of uremic patients reversibly inhibits RBC TPMT activity to a greater extent than normal plasma does and contains higher concentrations of endogenous methyl acceptors than normal plasma. Plasma TPMT inhibitors are not removed by hemodialysis. There are large individual variations in inhibition of RBC TPMT by plasma from patients with renal failure. Inhibition varied from 1% to 93% in 20 microliters of plasma from each of 20 randomly selected uremic patients. There was a positive correlation between the inhibition of TPMT and the content of endogenous methyl acceptors in uremic plasma (r = 0.914, n = 20, p < 0.001), but there was no significant correlation between degree of inhibition and urea nitrogen, serum creatinine, or hematocrit. The ability of plasma from individual uremic patients to inhibit TPMT also correlated with its ability to inhibit two other drug metabolizing methyltransferases in the RBC, catechol-O-methyltransferase and phenol-O-methyltransferase, RBC TMT activity is not altered in patients with uremia. The results of these and other studies of methyl conjugation in renal failure focus attention on the accumulation of methyl acceptor substrates in some of these patients and on the possible effects of these methyl acceptors on a variety of methylation reactions.
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PMID:Thiol S-methylation in uremia: erythrocyte enzyme activities and plasma inhibitors. 740 96

Tolcapone, a catechol-O-methyltransferase inhibitor, can interfere with the metabolism of levodopa and dopamine and could prolong the motor effect induced by levodopa in parkinsonian patients. To test this hypothesis, we studied the motor effect induced by three acute administrations of a dose of levodopa-benserazide (Madopar) with either 200 mg or 400 mg of tolcapone or placebo, in a double-blind latin-square design. The duration of the on-phase could be compared in 10 parkinsonian patients suffering from square-shaped motor effect. In comparison to placebo, 200 mg and 400 mg of tolcapone significantly increased the mean duration of the on-phase by 61.7 min ( +/- 19.4 SEM) and by 72.2 min ( +/- 18.5), respectively. This clinical effect is suggested to be related mainly to the increase in levodopa area under the curve and half-life induced by tolcapone. The intensity in dyskinesias was increased by 400 mg of tolcapone. Tolcapone appears to be well tolerated and could be helpful as an adjuvant treatment to levodopa in parkinsonian patients with motor fluctuations.
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PMID:Acute administration of levodopa-benserazide and tolcapone, a COMT inhibitor, Parkinson's disease. 863 84