Inhibition of rat liver catechol- O-methyltranferase by lanthanum, neodymium and europium

Abstract

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 La 3+, Nd 3+ and Eu 3+ 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 La 3+, Nd 3+ and Eu 3+ 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 La 3+ 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 La 3+, Nd 3+ and Eu 3+ are similar to those of the inhibition of COMT by Ca 2+. However, lanthanum, neodymium and europium are two to three orders of magnitude more potent inhibitors of COMT than is calcium.