Partially purified rat liver catechol-O-methyltransferase (COMT) is inhibited by lanthanum, and by the lanthanides, neodymium and europium. The 50 per cent inhibitory concentrations are 3 × 10-6, 1.2 × 10-6, and 8.5 × 10-7 M for La3+, Nd3+ and Eu3+ respectively. The inhibition of COMT by these ions is reversible. Lineweaver-Burk plots of the results of experiments in which the enzyme activity was measured in the presence of varying concentrations of magnesium, an activator of COMT, and different concentrations of La3+, Nd3+ and Eu3+ were compatible with non-competitive or "mixed" inhibition. Double reciprocal plots of the results of experiments in which COMT activity was determined in the presence of different concentrations of La3+ and varying quantities of the two co-substrates for the reaction, S-adenosyl-1-methionine and 3,4-dihydroxybenzoic acid, were also compatible with non-competitive or "mixed inhibition". The characteristics of the inhibition of rat liver COMT by La3+, Nd3+ and Eu3+ are similar to those of the inhibition of COMT by Ca2+. However, lanthanum, neodymium and europium are two to three orders of magnitude more potent inhibitors of COMT than is calcium.
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