Biomaterial Database

Molecular properties and inhibition kinetics of acetylcholinesterase obtained from rat brain and cockroach ganglion. 1990

A K Singh

Department of Veterinary Diagnostic Investigation, College of Veterinary Medicine, University of Minnesota, St. Paul 55108.

1. The molecular composition of acetylcholinesterase (AChE) obtained from cockroach neural, and rat brain tissues was different. Vertebrate enzyme exhibited a higher degree of polymerization than insect enzyme. 2. Acephate was a potent inhibitor of cockroach AChE, but a poor inhibitor of rat AChE. Unlike acephate, methamidophos was a potent inhibitor of both cockroach and rat enzymes. Acephate exhibited greater affinity for the cockroach-AChE than for the rat-AChE, and acephate phosphorylated the cockroach-AChE several times faster than the rat enzyme. The rate of phosphorylation of insect and rat AChE was similar in the presence of methamidophos. Solubilization of AChE by Triton X-100 altered the kinetics of inhibition of rat AChE by acephate. However, solubilization did not alter the kinetics of inhibition of rat AChE by methamidophos or the kinetics of inhibition of cockroach AChE by acephate or methamidophos. 3. The mechanism of acephate-cockroach AChE interaction was different than the mechanism of acephate-rat AChE interaction. It is proposed that both the rat and cockroach enzyme may contain, along with the anionic and esteratic sites, an "electron deficient" (ED) binding site which may exhibit selectivity for acephate and nefopam. The ED site in rat-AChE has allosteric properties, whereas the cockroach-AChE does not. It is also proposed that the ED site in cockroach-AChE may be situated in or adjacent to the active site and, therefore, acephate may be bound to the ED site such that the phosphate moiety of acephate interacts with the enzyme's "esteratic" site. Although nefopam also bound to the ED site in cockroach AChE, it did not inhibit the enzyme. This study also indicated that the ED site in rat-AChE may be peripheral to the active site, and that the binding of acephate to this site prevented the phosphorylation by methamidophos of the rat-AChE. Unlike acephate, methamidophos specifically bound to the active site in both the rat- and cockroach-AChE.

UI	MeSH Term	Description	Entries
D007306	Insecticides	Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.	Insecticide
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D009340	Nefopam	Non-narcotic analgesic chemically similar to ORPHENADRINE. Its mechanism of action is unclear. It is used for the relief of acute and chronic pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p26)	Acupan,Ajan,Fenazoxine,Nefopam Hydrochloride,Silentan Nefopam,Hydrochloride, Nefopam,Nefopam, Silentan
D009946	Organothiophosphorus Compounds	Compounds containing carbon-phosphorus bonds in which the phosphorus component is also bonded to one or more sulfur atoms. Many of these compounds function as CHOLINERGIC AGENTS and as INSECTICIDES.	Compounds, Organothiophosphorus
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011092	Polyethylene Glycols	Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.	Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
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
D003058	Cockroaches	Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.	Blaberidae,Blattaria,Blattidae,Blattodea,Cryptocercidae,Dictyoptera,Polyphagidae,Cockroach,Blattarias,Blattodeas,Cockroache,Cockroachs,Dictyopteras