Stereochemical course of the transmethylation catalyzed by histamine N-methyltransferase

The stereochemical course of the methyl group transfer catalyzed by histamine N-methyltransferase was studied using S-adenosylmethionine (AdoMet), which carried a chiral methyl group. The incubation of these AdoMet samples and histamine with a partially purified enzyme obtained from guinea pig brains gave the corresponding methylated histamine. The N-methylhistamine samples were degraded to convert the N-methyl group into the methyl group of acetate using a reaction sequence of known stereochemistry. The results of the configurational analysis of these acetate samples indicated that the enzymatic transfer of the methyl group from the sulfur of AdoMet to the nitrogen of histamine occurs with inversion of configuration.