Choline acetylase

Acetylcholine is the product of the reaction between choline and acetyl coenzyme A in the presence of choline acetylase (41). 

It is synthesized within the cholinergic neurons by the transfer of an acetyl group from acetyl coenzyme A to the organic base choline. The specific enzyme choline acetylase is essential for this reaction. Coenzyme A is widely distributed in the body and choline acetylase is synthesized in the cell bodies of the cholinergic neurons. 

FIGURE 14.4 The metabolism and actions of acetylcholine (ACh). CoA = coenzyme A CHAT = choline acetylase. 

FIGURE 43.6 Amitriptyline has potent anticholinergic properties. CHAT = choline acetylase CoA = coenzyme A ACh = acetylcholine. 

Acetylcholine is synthesized from acetyl coenzyme A (acetyl-CoA) and choline within the presynaptic terminal by the enzyme choline acetylase. The acetylcholine formed is stored in small, lightly staining synaptic vesicles that are concentrated around the synaptic contact area. The release of acetylcholine is calcium dependent. The entire content of a synaptic vesicle is released into the cleft in an all-or-none manner, where it interacts with its receptors and then is rapidly destroyed by acetylcholinesterase. Under normal circumstances, the half-life for acetylcholine in the synaptic cleft is about 1 ms. The acetylcholine is hydrolyzed to choline and acetate, and the choline is actively pumped back into the presynaptic terminal to be used to synthesize more acetylcholine. 

Sorbo, S. Bo, and Schuberth, Jan, Measurements of Choline Acetylase. Supp. 

Choline Acetylase, Measurements of (SoHao and Schahcrih). Supp. 275... 

Other potential targets of cholinergic stimulation or blockade by drugs include the cornea, lens, and retina. The corneal epithelium contains the neurotransmitter acetylcholine and the enzymes choline acetylase... 

Hlley and Burgen (58) measured also the choline acetylase and acetylcholinesterase activities of selected areas of the brain. In an attempt to determine whether the concentration of muscarinic receptors in a location was related to either of these enzyme activities. The amount of Che labeled prppylbenzllylchollne mustard bound was not well correlated with either the choline acetylase or the acetylcholinesterase activity there was a modest correlation between binding of the model agonist by synapcosomes and membranes prepared from nine areas of brain and the choline acetylase activities of the same areas, but It was far from precise. 

Yamamura et al. found that uptake of the label by various areas of brain had a tendency to be correlated with choline uptake and with choline acetylase activity. 

Yamamura and Snyder (195) found that Interruption of the septal hippocampal tract, and elimination thereby of cholinergic afferents to the hippocampus, reduced by about 70X the activity of choline acetylase In homogenates of the hippocampus, but did not alter the binding of [ H]3-qulnuclldli l benzllate by the particles of such homogenates. They proposed, as a possible explanation, chat... 

Hebb, C. O. and Silver, A. (1963) The effect of transection on the level of choline acetylase in the goat s sciatic nerve. J. Physiol. (Lond.), 169,41P-42P. 

McCaman, R. E., Rodriguez de Lores Arnaiz, G. and De Robertis, E. (1965) Species differences in subcellular distribution of choline acetylase in the CNS. A study of choline acetylase, acetylcholinesterase, 5-hydroxytryptophan decarboxylase, and monoamine oxidase in four species. J. Neurochem., 12, 927-935. 

Evidence that acetylcholine is a chemical mediator of synaptic transmission elsewhere in the central nervous system is circumstantial but convincing. Acetylcholine is the transmitter substance from motor nerves, preganglionic autonomic fibres and the postganglionic fibres of the parasympathetic system to their respective effector cells. In all these fibres, the activity of choline acetyltransferase (choline acetylase), the enzyme responsible for the synthesis of acetylcholine, is high. Conversely, its activity is negligibly low in sensory nerve fibres and transmission from these fibres is demonstrably non-cholinergic in nature . It is reasonable, therefore, to... 

Until 1953, biochemical interest in this neurohumoral agent centered round its biosynthesis via choline acetylase and its breakdown by cholinesterases. Biochemists became particularly interested, for example, in highly specific anticholinesterases (Section II, B), studies which have implications other than academic ones. The possibility that acetylcholine might affect metabolic processes otherwise than as a result of direct stimulation of peripheral nerve had not been considered until the Hokins demonstrated that 10 -10 M concentrations of the drug in the presence of eserine (physostigmine) stimulated the uptake of P -labeled inorganic orthophosphate into the phospholipids of secreting sites of the pancreas (Hokin and Hokin, 1953,1954). They further demonstrated that... 

ALAndrostene-3,17-dione, effect on D-amino acid oxidase, X, 356 on choline acetylase, X, 362 on oxidation of a-glycerophosphate, X, 359, 360... 

Choline acetylase, adrenal cortex and, X, 348-349 effect of steroid hormones on, X, 362, 367... 

Acetyl-CoA choline 0-acetyltransferase (EC 2.3.1.6) or choline acetylase Acelyl-CoA CoA... 

Esters of carboxylic acids are prominent among the chemical structures of biological systems. The biosyntheses of only a few of the naturally occurring esters have been studied enzymatically. Among the known reactions are the syntheses of acetylchohne and of phosphatidic acids. Acetylcholine is formed by choline acetylase, which has been purified from nervous tissue. Nachmansohn and associates have prepared choline acetylase from rat brain, the electric organ of the electric eel, squid ganglia, and other tissues. It has been detected in muscle also, but not in liver or kidney. The reaction is very similar to the acetylation of amines. 

Choline acetylase and the amine-acetylating enzyme are distinct, and do not cross react with the substrates of the other enzyme. 

Choline Acetvlase - Choline acetyltransferase, the enzyme responsible for the synthesis of acetylcholine from choline and acetylcoenzyme A, was first studied in cell-free preparations by Nachmansohn and Machado O. Even though the Importance of choline acetylase Is as great as that of acetylcholinesterase, much less Interest has been centered on the enzyme responsible for the synthesis of acetylcholine than on the enzyme responsible for Its hydrolysis, until fairly recently. The properties of choline acetyltransferase isolated from squid ganglia... 

The report that S-bromoacetyl coenzyme A is a potent inhibitor of choline acetylase , was followed by the recent report of a group of styrylpyrldine analogs also capable of inhibiting this enzyme OS, One of these, 4-(l—naphthylvinyl)pyridine is claimed to inhibit choline acetylase without affecting acetylcholinesterase, Quatemlzatlon of this compound permits it to inhibit both enzymes. 

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