Microsomal phosphatidylethanolamine methyltransferase: Inhibition by S‐adenosylhomocysteine

Abstract

Inhibition by S-adenosylhomocysteine (AdoHcy) of the three reactions of phosphatidylethanolamine methyltransferase which catalyzes the production of phosphatidylcholine from phosphatidyl-ethanolamine in guinea pig and rat liver microsomes has been evaluated. Five of the six methylation reactions in these two species exhibit greater affinity for inhibitor, AdoHcy, than for substrate, S-adenosylmethionine (AdoMet). The Ki values for the rate-limiting reactions were 3.8 μM and 68 μM in rat and guinea pig livers, respectively. An AdoMet:AdoHcy ratio of 12∶1 in developing liver was found to decline to a constant value in the adult of 5∶1. The concentration of AdoHcy in rat and guinea pig liver increases markedly following death of the animal. A concomitant decrease in the AdoMet level was observed in guinea pig liver. A comparison of phosphatidylethanolamine methyl-transferase activity with the hepatic concentrations of AdoMet and AdoHcy in mouse, rat, rabbit and guinea pig is presented. Regulation of the methylation pathway is discussed.