Biomaterial Database

Kinetics of human erythrocyte acetylcholinesterase inhibition by a novel derivative of physostigmine: phenserine. 1998

A A al-Jafari, and M A Kamal, and N H Greig, and A S Alhomida, and E R Perry

Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. JAFARI@KSU.EDU.SA

The effect of phenserine, a novel cholinesterase inhibitor, was assessed for the first time on kinetic parameters of human erythrocyte acetylcholinesterase (AChE). Phenserine (0.025-0.40 microM) inhibited the activity of human erythrocyte AChE in a concentration-dependent fashion, the IC50 was 0.0453 microM. The Michaelis-Menten constant (K(m)) for the hydrolysis of acetylthiocholine iodide was found to be 0.124 mM and the Vmax was 0.980 mumol/min/mg protein. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the noncompetitive type. The value of Ki was estimated as 0.048 microM by the primary and secondary replots of the Dixon as well as secondary replots of the Lineweaver-Burk plot. A novel relationship between Ki and substrate concentration was also identified which permits more precise prediction of the specific type of noncompetitive inhibition of various enzymes by a wide variety of drugs, chemicals and, in some circumstances, by their own substrates.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D010830	Physostigmine	A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.	Eserine
D002800	Cholinesterase Inhibitors	Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.	Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000110	Acetylcholinesterase	An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7.	Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D000122	Acetylthiocholine	An agent used as a substrate in assays for cholinesterases, especially to discriminate among enzyme types.	(2-Mercaptoethyl)trimethylammonium Acetate