Catechol-O-methyltransferase biochemical genetics: Human lymphocyte enzyme

Susan Sladek-Chelgren, Richard M. Weinshilboum

Research output: Contribution to journalArticle

32 Scopus citations

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 and at a MgCl2 concentration of 0.67 mm. The apparent Kmvalue for 3,4-dihydroxybenzoic acid, the catechol substrate for the reaction, was 1.2×10-5m and that for S-adenosyl-l-methionine, the methyl donor, was 2.3×10-6m. 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/106 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<0.001) when lymphocyte enzyme activity was expressed per milligram of protein and 0.649 (P<0.001) when lymphocyte activity was expressed per 106 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.

Original languageEnglish (US)
Pages (from-to)1037-1053
Number of pages17
JournalBiochemical Genetics
Volume19
Issue number11-12
DOIs
StatePublished - Dec 1981

Keywords

  • biochemical genetics
  • catechol-O-methyltransferase
  • catecholamines
  • erythrocyte enzymes
  • lymphocyte enzymes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry
  • Molecular Biology
  • Genetics

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