Gastric histamine methyltransferase: different methylation rates for enantiomers of side-chain methylated histamine analogues using a highly purified enzyme preparation.

The inhibitor/activator and substrate properties of enantiomers of two methylated histamines (MH) were investigated using a histamine methyltransferase preparation which was purified 1207-fold from pig fundic mucosa by ultracentrifugation, ion-exchange chromatography on DEAE-cellulose and preparative electrofocusing. In 1-100 microM concentrations, S-alpha-MH and R-alpha-MH were acceptor substrates as good as histamine itself. When substrate concentrations were increased to 1 mM these substances were methylated to an even greater extent than histamine, since they did not exert substrate inhibition on HMT. Introduction of a further methyl-group into the N alpha-position reduced acceptor substrate properties drastically. A difference in methylation was then seen since R-alpha,N alpha-DMH was a better substrate than S-alpha,N alpha-DMH. Whereas alpha-MH's could not activate HMT the alpha,N alpha-DMH's did. The poorer the substrate affinity of the investigated substances was, the better they were able to activate HMT.