PRODUCT INHIBITION OF RAT BRAIN HISTAMINE‐N‐METHYLTRANSFERASE

— The inhibition of S‐adenosylmenthionine: histamine‐N‐methyltransferase (EC 2.1.1.8; HMT) by its products, 3‐methylhistamine (3‐MetHm) and S‐adenosyl‐l‐homocysteine (SAH), was examined using a preparation of the enzyme which was partially purified from rat brains. SAH was found in in vitro experiments, to be a competative inhibitor of HMT in relation to S‐adenosyl‐l‐methionine (SAM), with a Ki= 5.6 μM. SAH was shown to be a non‐competitive inhibitor with respect to histamine (Hm) (Ki= 5.0 μM). The Km's for SAM and Hm were 10.2 and 3.0 μM respectively. On the other hand, 3‐MetHm was determined to be a non‐competitive inhibitor of HMT with respect to Hm (Ki= 8.7 μM) and an uncompetitive inhibitor with respect to SAM (Ki= 9.6 μM). These results suggest that the addition of the substrate to, and the release of products by, HMT occurs sequentially. In the nomenclature Of Cleland (1963) the reaction is seemingly of the ‘ordered Bi‐Bi’ type.