S-Methylation of D- and L-penicillamine by human erythrocyte membrane thiol methyltransferase.

Human red blood cell (RBC) membranes contain a thiol methyltransferase activity that catalyzes the S-methylation of 2-mercaptoethanol (2-ME). These experiments were performed to determine whether human RBC membranes contain enzymes that can catalyze the S-methylation of D- and L-penicillamine, to determine whether those enzymes are similar to the RBC membrane thiol methyltransferase that catalyzes the S-methylation of 2-ME, and to determine whether lipophilic conjugates of the S-methyl metabolites of D- and L-penicillamine are formed by RBC membranes. Human RBC membranes were able to catalyze the S-methylation of D- and L-penicillamine. The apparent Michaelis (Km) constants for D- and L-penicillamine were 7.53 and 7.27 mM, respectively. However, the Vmax value for L-penicillamine was more than 2.5 times greater than the Vmax value for D-penicillamine. D- and L-Penicillamine methyltransferases and 2-ME thiol methyltransferase were similar with respect to their subcellular distributions, inhibitor sensitivities, and thermal stabilities. In addition, when methyltransferase activities for 2-ME and for D- and L-penicillamine were measured in RBC membranes from 19 individual subjects, there were highly significant correlations among all three activities (r greater than 0.98, p less than 0.001 for all three comparisons). These observations suggest either that a single enzyme in the human RBC membrane catalyzes the S-methylation of all three compounds, or, less likely, that these reactions are catalyzed by three separate enzymes that are regulated in parallel and have similar properties. Experiments were then performed to identify the products of the penicillamine methylation reactions.(ABSTRACT TRUNCATED AT 250 WORDS)