Choline and

CjHiaNO, [Mc3NCH= CH2] OH. A liquid forming a crystalline trihydrate, It is present free and combined in brain and other animal and vegetable products and is formed as a product of putrefaction of lecithin. It can be prepared synthetically from choline and decomposes easily to trimethylamine. neutralization, heat of The amount of heat evolved when I g equivalent of an acid is neutralized by 1 g equivalent of a base. For strong acids and strong bases in dilute solution the only reaction which occurs is H -h OH ---> H2O and the heat of neutral-... 

Vitamin Bj 2 is concerned in the biosynthesis of methyl groups of choline and methionine. 

The names choline and betaine are retained for unsubstituted compounds. 

Enzyme-Catalyzed Reactions Enzymes are highly specific catalysts for biochemical reactions, with each enzyme showing a selectivity for a single reactant, or substrate. For example, acetylcholinesterase is an enzyme that catalyzes the decomposition of the neurotransmitter acetylcholine to choline and acetic acid. Many enzyme-substrate reactions follow a simple mechanism consisting of the initial formation of an enzyme-substrate complex, ES, which subsequently decomposes to form product, releasing the enzyme to react again. 

P. A. Anderson, Signficance of Indispensable Mmino A.cids, Choline, and Taurine in Feline Nutrition, Ph.D. dissertation. University of Illinois at Urbana-Champaign, 1979. 

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

Choline was isolated from ox bile in 1849 by Strecker. During 1900 to 1920, observations led to interest in the vasodepressor properties of the esters of choline, and in the 1920s it was shown that acetylcholine was presumably the "vagus-substance." The nutritional importance of choline was recognized in the 1930s, when it was found that choline would prevent fatty infiltration of the Hver in rats. Subsequent observations showed that choline deficiency could produce cirrhosis (1) or hemorrhagic kidneys (2) in experimental animals under various conditions. 

Fatty infiltration of the Hver has been observed to precede cirrhosis in experimental animals receiving diets low in choline and other substances that can furnish labile methyl groups, and can thus serve as precursors of choline. 

Fig. 1. The choline and methionine cycles showing the origin and disposition of labile methyl groups. FAH = tetrahydrofolic acid CH3BJ2 = methylated...

An earlier procedure for the production of choline and its salts from natural sources, such as the hydrolysis of lecithin (23), has no present-day apphcation. Choline is made from the reaction of trimethyl amine with ethylene oxide [75-21-8] or ethylene chlorohydrin [107-07-5J. 

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

Figure 1 Chemical structure and space-filling representation of a phosphatidylcholine, DPPC. Different parts of the molecule are referred to by the labels at the left together the choline and phosphate are referred to as the headgroup, which is zwitteriomc. In the space-filling model, H atoms are white, O and P gray, and C black. (From Ref. 55.)...

Sinapine acid sulphate, CjgH240jN. HSO4. SHjO, crystallises in leaflets, m.p. 127° (188°, dry). The thiocyanate, CigHj OjN. SCN. HjO, forms pale yellow needles, m.p. 178° iodide, m.p. 185-6°. When the thiocyanate is warmed with alkalis there is formed choline and sinapic acid, the acid was investigated by Remsen and Coale, and... 

Arachis hypogcea L. Arachine, CgHj ONj, with choline and betaine. Yellowish-green syrup crystalline platinichloride, m.p. 216° and aurichloride produces transient narcosis in frogs and rabbits with partial paralysis (Mooser, Landw. Versuchs-Stat., 1904, 60, 321 Chem. Soc. Abstr., 1905, [i], 79)). 

Chrysanthemum cineraricefolium Bocc. Chrysanthemine is a mixture of choline and stachydrine (Marino-Zuco, Chem. Soc. Abstr., 1891, 60, 333 1892, 62, 84 Yoshimura and Trier, Zeit. Physiol. Chem., 1912, 77, 290). 

Choline, a component of the phospholipids in cell membranes, can be prepared by Sn2 reaction of trimethylamine with ethylene oxide. Show the structure of choline, and propose a mechanism for the reaction. 

While these functions can be a carried out by a single transporter isoform (e.g., the serotonin transporter, SERT) they may be split into separate processes carried out by distinct transporter subtypes, or in the case of acetylcholine, by a degrading enzyme. Termination of cholinergic neurotransmission is due to acetylcholinesterase which hydrolyses the ester bond to release choline and acetic acid. Reuptake of choline into the nerve cell is afforded by a high affinity transporter (CHT of the SLC5 gene family). 

Extracellular degradation removes acetylcholine, the neuropeptides and ATP. Acetylcholine is rapidly hydrolyzed to choline and acetate by acetylcholinesterase. The enzyme is localized in both the presynaptic and the postsynaptic cell membrane and splits about 10,000 molecules of acetylcholine per second. 

One excellent UV protector for foods is PABA, a B vitamin. Likewise, many of the same antioxidants we ingest as health supplements—such as vitamin C and a similar chemical, erythorbic acid vitamin E and lecithin, a source of the important nutrients choline and inositol—occur naturally in food. 

Triacylglycerols and some phosphoglycerols are synthesized by progressive acylation of glycerol 3-phosphate. The pathway bifurcates at phosphatidate, forming inositol phospholipids and cardiolipin on the one hand and triacylglycerol and choline and ethanolamine phospholipids on the other. 

Apart from inhibiting the uptake of choline and hence its availability for ACh synthesis, with hemicholinium (see above), there are no drugs that directly affect the actual storage or release of ACh. Some experimental tools have, however, been used such as vesamicol, which appears to block the packaging of ACh into its vesicles and thus initiates the slow rundown of releasable vesicular ACh. Some toxins also inhibit ACh release. 

Flentge, F, Venema, K, Koch, T and Korf, J (1997) An enz5mie-reactor for electrochemical monitoring of choline and acetylcholine. Applications in high-performance liquid chromatography, brain tissue, microdialysis and cerebral fluid. Annal. Biochem. 204 305-311. 

ACh is metabolised extraneuronally by the enzyme acetylcholinesterase, to reform precursor choline and acetate. Blocking its activity with various anticholinesterases has been widely investigated and some improvement in memory noted. Such studies have invariably used reversible inhibition because of the toxicity associated with long-term irreversible inhibition of the enzyme. Physostigmine was the pilot drug. It is known to improve memory in animals and some small effects have been seen in humans (reduces number of mistakes in word-recall tests rather than number of words recalled), but it really needs to be given intravenously and has a very short half-life (30 min). 

King GM (1984) Metabolism of trimethylamine, choline and glycine betaine by sulfate-reducing and metha-nogenic bacteria in marine sediments. Appl Environ Microbiol 48 719-725. 

FIG. 14 C NMR spectra of the EPC SUV in the presence and the absence of BPA, at the EPC atom sites of (a) carbonyl, (b) olefinic, (c) choline and glycerol, and (d) methylene and methyl carbons. In each spectral region, the upper trace represents the EPC spectrum before the addition of BPA, while the lower is that after the BPA delivery. Asterisks denote the signals of the reference, DSS. (From Ref. 47. Copyright 1999 American Chemical Society.)... 

Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.35,38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients PN caused reversal of steatosis. 

Analogues of phosphatidyl ethanolamine, phosphatidyl choline, and phosphatidic acid with pantoic acid skeleton were prepared by phosphorylation with the respective phosphoric mono-, bis-, and tristriazolide [17]... 

Acetylcholine, which is set free from vesicles present in the neighbourhood of the presynaptic membrane, is transferred into the recipient cell through this channel (Fig. 6.25). Once transferred it stimulates generation of a spike at the membrane of the recipient cell. The action of acetylcholine is inhibited by the enzyme, acetylcholinesterase, which splits acetylcholine to choline and acetic acid. 

A number of substituted p-aminoacetates inhibit the enzyme cholinesterase. The main function of this enzyme is to hydrolyze acetyl choline and thereby terminate the action of that substrate as a neurotransmitter. Such inhibition is functionally equivalent to the administration of exogenous acetylcholine. Direct administration of the neurotransmitter substance itself is not a useful therapeutic procedure due to rapid drug destruction and unacceptable side... 

The primary mechanism used by cholinergic synapses is enzymatic degradation. Acetylcholinesterase hydrolyzes acetylcholine to its components choline and acetate it is one of the fastest acting enzymes in the body and acetylcholine removal occurs in less than 1 msec. The most important mechanism for removal of norepinephrine from the neuroeffector junction is the reuptake of this neurotransmitter into the sympathetic neuron that released it. Norepinephrine may then be metabolized intraneuronally by monoamine oxidase (MAO). The circulating catecholamines — epinephrine and norepinephrine — are inactivated by catechol-O-methyltransferase (COMT) in the liver. 

Dale, H. H. (1914). The action of certain esters and ethers of choline and their relation to muscarine. J Pharmacol 6, 147-90. 

---