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.