Book: Cholines, Acetylcholine and Cholinesterase

Overview
Martin H. Fischer’s 1941 monograph surveys the chemistry, physiology, and clinical relevance of choline compounds, acetylcholine, and the enzyme systems that rapidly hydrolyze them. It consolidates three decades of discoveries following the identification of acetylcholine as a biological mediator, tracing a path from basic chemical characterization through organ and systemic physiology to therapeutic application. The book positions the cholinergic system at the crossroads of autonomic function, neuromuscular transmission, and metabolic health, while also cataloging methodological approaches and experimental caveats that defined the field in the interwar period.

Chemistry of cholines
Fischer begins with the quaternary ammonium base choline, relating its occurrence in phospholipids such as lecithin and its conversion to derivatives including betaine and acetylcholine. He emphasizes the physicochemical properties conferred by the quaternary nitrogen, the reactivity of the ester linkage in acetylcholine, and the susceptibility of these compounds to enzymatic degradation. The text distinguishes endogenous biosynthetic pathways and dietary sources, reflecting contemporary interest in choline as a lipotropic factor with implications for hepatic fat metabolism.

Acetylcholine as a physiological mediator
Drawing on the work of Loewi and Dale, the book presents acetylcholine as a principal transmitter at parasympathetic nerve endings and a key agent at the neuromuscular junction. Fischer details its effects on smooth muscle, glandular secretion, cardiac function, and vascular tone, emphasizing organ specificity and dose dependence. He highlights the duality of muscarinic and nicotinic actions, inferred pharmacologically through antagonists like atropine and curare, and explores species differences and tissue context that complicate simple generalizations. The short-lived nature of acetylcholine’s effects is repeatedly tied to rapid enzymatic hydrolysis.

Cholinesterase: distribution and function
A central section catalogues cholinesterase activity across tissues and species, with particular attention to red blood cells, nervous tissue, muscle, and liver. Fischer distinguishes the “true” (acetyl-) cholinesterase, most efficient at hydrolyzing acetylcholine, from broader “pseudocholinesterase” activities that act on various choline esters, anticipating later isoenzyme classifications. He examines the enzyme’s physiological role as a terminator of cholinergic signaling and as a determinant of acetylcholine’s pharmacodynamic profile.

Methods and measures
The book is meticulous about technique: preparation of tissue extracts, substrate purity, control of pH and temperature, and the pitfalls of manometric, titrimetric, and bioassay approaches. Fischer underscores variability arising from tissue handling, nonenzymatic hydrolysis, and inhibitor contamination, urging standardized conditions to enable meaningful comparison. Kinetic interpretations are cautious and framed by the limits of the instrumentation and analytical chemistry of the time.

Pharmacology and inhibitors
Fischer surveys cholinesterase inhibitors, reversible agents such as physostigmine and neostigmine, showing how they magnify and prolong acetylcholine’s actions, thereby serving both as experimental tools and as therapeutics. He contrasts these with antagonists of acetylcholine’s receptors, clarifying how receptor blockade and enzyme inhibition produce distinct physiological signatures. The therapeutic relevance encompasses myasthenia gravis, glaucoma, and postoperative ileus, alongside risks of toxicity, desensitization, and autonomic imbalance.

Nutrition, pathology, and open questions
Beyond neurotransmission, the text treats choline as a nutritional factor, tying deficiency to fatty liver and impaired lipoprotein export. Fischer notes alterations of cholinesterase activity in disease states and the potential diagnostic value of enzyme assays, while acknowledging the uncertainties in causation versus correlation. He ends by delineating unresolved problems, how and where acetylcholine is synthesized and stored, the precise identity and regulation of multiple cholinesterases, and the reconciliation of pharmacological classifications with emerging biochemical evidence, setting an agenda for postwar neurochemistry.

Significance
Fischer’s synthesis provides an authoritative framework that links chemical structure to biological function and clinical practice. By integrating meticulous methodological guidance with a balanced appraisal of evidence, the book helped crystallize the cholinergic paradigm and shaped subsequent research on synaptic transmission and enzyme inhibition.