Biomaterial Database

Kinetic evidence for the allosteric substrate inhibition of human erythrocyte acetylcholinesterase. 1980

E Niday, and C S Wang, and P Alaupovic

Kinetic experiments described in this study were carried out with an electrophoretically and immunologically homogeneous acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) preparation isolated from human erythrocyte membranes. At low concentration of substrates, the acetylcholinesterase-catalyzed reaction follows Michaelis-Menten kinetics. In comparative studies using acetylthiocholine and acetylcholine as substrates, the corresponding Km values were 150 +/- 30 microM and 200 +/- 20 microM, respectively. At low concentrations of both substrates, Hill plots indicated the existence of either a single or multiple independent active site(w). The inhibition mechanism of acetylcholinesterase by high concentration of substrates were studied by utilizing a new kinetic parameter, delta, which allows discrimination between the competitive and uncompetitive types of substrate inhibitions (Wang, C.-S. (1977) Eur. J. Biochem. 78, 568--574). This kinetic approach provided evidence that the inhibition of acetylcholinesterase by excess substrate was effected by its interaction with multiple allosteric sites on the enzyme.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
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
D000494	Allosteric Regulation	The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.	Regulation, Allosteric,Allosteric Regulations,Regulations, Allosteric