Book: Cholinesterases

Overview
Martin H. Fischer’s 1949 monograph surveys the enzymes that hydrolyze choline esters, assembling a then-definitive account of cholinesterases as biological catalysts central to neurotransmission, pharmacology, and toxicology. The book organizes a rapidly growing literature into a coherent framework that distinguishes enzyme types, clarifies their chemical behavior, and links laboratory findings to physiological and clinical phenomena.

Historical frame and definitions
Fischer situates cholinesterases in the wake of acetylcholine’s recognition as a transmitter and the classic work of Dale and Loewi, showing how the need to terminate cholinergic signals made a fast, highly specific esterase not merely plausible but necessary. He adopts the two-enzyme schema that had emerged in the 1940s: a “true” acetylcholinesterase associated with nerve tissue, red cells, and endplates, and a broader “pseudocholinesterase” abundant in plasma and liver. He stresses that these are operational distinctions grounded in substrate preference, tissue distribution, and inhibitor sensitivity rather than mere nomenclature.

Chemistry and kinetics
The core chapters analyze substrate specificity, noting the importance of the quaternary ammonium group and the marked preference of acetylcholinesterase for short-chain acyl groups, especially acetyl. Fischer summarizes evidence for a charged binding site and an esteratic locus, an early two-site model, accounting for the remarkable speed and selectivity. He presents simple Michaelis–Menten treatments of initial rates, considers effects of ionic strength and pH on turnover, and discusses the reversible formation of an acyl-enzyme intermediate as a working hypothesis consistent with the behavior of related esterases.

Distribution and physiology
Fischer catalogs tissue activities across species, emphasizing the concentration of “true” cholinesterase at cholinergic synapses and neuromuscular junctions and the ubiquity of the serum enzyme. He relates enzyme abundance to physiological demand: high activity where rapid signal termination is essential; broader activity where detoxication of circulating esters may be advantageous. The text repeatedly ties enzymatic properties to function, arguing that the temporal precision of autonomic and somatic cholinergic signaling depends on acetylcholinesterase’s extraordinary catalytic capacity.

Inhibitors and pharmacological uses
A major section treats anticholinesterase agents. Fischer details the reversible carbamate inhibitors typified by physostigmine and the quaternary ammonium drugs used therapeutically to augment cholinergic transmission, as in myasthenia gravis and certain paralytic ileus states. He contrasts these with the potent, often irreversible organophosphorus compounds introduced in the 1930s and 1940s, including laboratory reagents and wartime agents, outlining their kinetics of inhibition and the clinical picture of cholinergic excess. Protective measures, atropine, assisted ventilation, and careful dosing, are discussed in practical terms.

Methods and measurement
The methodological chapters review titrimetric and manometric techniques for tracking acid formation during acetylcholine hydrolysis, color indicators and pH-stat approaches for routine assays, and biological assays on isolated organ preparations to link enzyme inhibition with physiological response. Procedures for crude purification, stability, and storage are given, with attention to artefacts introduced by salts, detergents, and tissue homogenization.

Clinical and toxicological implications
Fischer synthesizes clinical observations: variability of serum cholinesterase activity, heightened sensitivity to certain anesthetic agents and muscle relaxants in individuals with low plasma activity, and the hazards posed by agricultural organophosphates. He frames cholinesterase measurements as useful diagnostic indices and emphasizes the therapeutic balance between enhancing cholinergic tone and avoiding toxicity.

Unresolved problems and outlook
The book closes by identifying open questions of 1949: the precise molecular nature of the active site, the full physiological role of serum cholinesterase, the relationship between structure and inhibitor specificity, and the need for more refined purification and localization methods. By distilling disparate findings into a structured account, Fischer provides both a reference and a roadmap for postwar research on cholinergic enzymes.