Methyl conjugation in uraemia: catechol‐O‐methyltransferase.

1 Erythrocyte (RBC) catechol‐9‐methyltransferase (COMT) activity is significantly higher in erythrocytes from uraemic patients on maintenance haemodialysis, 18.7 +/‐ 1.4 units/ml RBC (mean +/‐ s.e. mean, n = 22) than in the blood of randomly selected subjects, 12.0 +/‐ 0.2 units/ml (mean +/‐ s.e. mean, n = 557, P < 0.001). 2 Uraemic plasma contains larger quantities of endogenous methyl acceptors than does normal plasma, and it reversibly inhibits RBC lysate COMT activity to a greater degree than does normal plasma. 3 There are large individual variations in the degree of inhibition of RBC COMT activity plasma from patients with renal failure. Inhibition varied from 10‐43% when 40 microliters plasma from each of 19 randomly selected uraemic patients was tested, and there as a direct correlation between the inhibition of COMT by plasma from an individual uraemic patient and its content of endogenous methyl acceptors (r = 0.64, n = 19, P < 0.01). 4 Kinetic studies with pooled uraemic plasma demonstrate that inhibition of COMT by uraemic plasma is uncompetitive with respect to both the catechol substrate and the methyl donor for the reaction, S‐adenosyl‐L‐ methionine. 5 Plasma from uraemic patients does not inhibit partially purified rat liver COMT, an observation which suggests that the inhibition is not due to a direct effect on COMT but requires the presence of other constituents of the RBC lysate, perhaps other methyltransferase enzymes. 1980 The British Pharmacological Society