Handbook of psychopharmacology

Molecular and cellular biology of cholinesterases

Organophosphorus and carbamate insecticides are toxic to insects and mammals by virtue of their ability to inactivate the enzyme acetylcholinesterase. This review addresses the mechanism of inhibition of acetylcholinesterase by organophosphorus and carbamate esters, focusing on structural requirements necessary for anticholinesterase activity. The inhibition of acetylcholinesterase by these compounds is discussed in terms of reactivity and steric effects. The role of metabolic activation or degradation in the overall intoxication process is also discussed.

Mechanism of action of organophosphorus and carbamate insecticides.

Butyrylcholinesterase is a serine hydrolase related to acetylcholinesterase that catalyses the hydrolysis of esters of choline, including acetylcholine. Butyrylcholinesterase has unique enzymatic properties and is widely distributed in the nervous system, pointing to its possible involvement in neural function. Here, we summarize the biochemical properties of butyrylcholinesterase and review the evidence that this enzyme has important roles in cholinergic neurotransmission and could be involved in other nervous system functions and in neurodegenerative diseases.

Neurobiology of butyrylcholinesterase.

Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: an alternative to radioimmunoassay.

The mechanism of cholinergic neurotransmission requires the rapid inac­ tivation of acetylcholine (Dale 1914). Loewi & Navratil showed in 1926 that acetylcholine can be destroyed by an enzyme that exists in aqueous extracts of frog tissues. An esterase that specifically hydrolyzes choline esters was characterized in horse serum by Stedman et al (1932), who called it choli­ nesterase. It was later found that blood cells also contain a high level of acetylcholine-hydrolyzing activity (Stedman & Stedman 1935). Alles & Hawes (1940) subsequently found that in human blood the serum and cell enzymes are qualitatively different; Mendel et al (1943a) showed that, al­ though the serum enzyme hydrolyzes butyrylcholine or propionylcholine faster than acetylcholine [as already noted by Stedman et al (1932)], the cell-bound enzyme acts preferentially on acetylcholine, at low substrate concentration. The particulate enzyme also presents a characteristic excess substrate inhibition, so that its activity varies, in a bell-shaped manner, as a function of substrate concentration (Mendel & Rudney 1943). These two activities exist in all classes of vertebrates. The serum enzyme (Be 3.1.1.8) varies somewhat in its specificity, notably in the relative rates of hydrolysis of propionylcholine and butyrylcholine (Augustinsson 1959a,b). The serum enzyme was called originally "nonspecific" cholineste­ rase, or "pseudocholinesterase" (Mendel et al 1943, Mendell & Rudney 1943). In contrast, the erythrocyte enzyme (EC 3.1.1.7) was considered the

J Massoulié

Papers

The Molecular Forms of Cholinesterase and Acetylcholinesterase in Vertebrates