Aryl acylamidase of monkey brain and liver: response to inhibitors and relationship to acetylcholinesterase

Abstract

The serotonin sensitive aryl acylamidase (aryl acylamide amidohydrolase EC 3.5.1.13) of monkey brain was compared with the liver enzyme. Although the two enzymes showed some similarities in their properties such as pH optima, the effect of metal ions and thiol agents, they significantly differed in their mol. wt and response to inhibitors. The liver enzyme had a higher mol. wt as observed by gel filtration on Sepharose 6B and a greater heat stability. The brain enzyme was inhibited specifically by the amines serotonin and tryptamine as well as by acetylcholine and its analogues and homologues in a non-competitive manner. The liver enzyme was unaffected by the above mentioned amines or acetylcholine but it was non-competitively inhibited by indole-3-acetic acid and indole-3-propionic acid both compounds having no effect on the brain enzyme. Eserine, a strong competitive inhibitor of acetylcholinesterase, at 10^-7M inhibited the brain aryl acylamidase to 75 per cent leaving the liver enzyme unaffected. Eserine inhibition of the brain enzyme was non-competitive. From Dixon plots serotonin, acetylcholine and eserine were shown to act at the same site on brain aryl acylamidase. The inhibition of the brain enzyme by eserine and acetylcholine, the elution of both aryl acylamidase and acetylcholinesterase activities in the same fractions during gel filtration and the regional distribution of aryl acylamidase in the brain suggested the association of aryl acylamidase with acetylcholinesterase in the brain though not in the liver.