Enantiomer effects of huperzine A on the aryl acylamidase activity of human cholinesterases.

Darvesh Sultan, Walsh Ryan, Martin Earl
Cellular and molecular neurobiology, 2003

Abstract

1. Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8) are serine hydrolase enzymes that catalyze the hydrolysis of acetylcholine. 2. (-) Huperzine A is an inhibitor of AChE and is being considered for the treatment of Alzheimer's disease. 3. In addition to esterase activity, AChE and BuChE have intrinsic aryl acylamidase activity. 4. The function of aryl acylamidase is unknown but has been speculated to be important in Alzheimer pathology. 5. Kinetic effects of (-) huperzine A and (+/-) huperzine A on the aryl acylamidase activity of human cholinesterases were examined. 6. (-) Huperzine A inhibited the aryl acylamidase activities of both AChE and BuChE. 7. (+/-) Huperzine A inhibited this function in AChE but stimulated BuChE aryl acylamidase suggesting that the (+) enantiomer is a powerful activator of this enzyme activity. 8. The two huperzine enantiomers may prove to be useful tools to examine the function of aryl acylamidase activity, including its role in Alzheimer pathology.

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