Choline functions

Choline functions in fat metaboHsm and transmethylation reactions. Acetylcholine functions as a neurotransmitter in certain portions of the nervous system. Acetylcholine is released by a stimulated nerve cell into the synapse and binds to the receptor site on the next nerve cell, causing propagation of the nerve impulse. 

Tubules have also been prepared by swelling thin films of polymerizable diacetylenic phosphatidylhydroxyethanol (choline functionally in 21 is replaced by hydroxyethanol) in aqueous metal ion solutions above the phase transition temperature of the lipid. Various cylindrical structures were observed upon swelling the lipid in the presence of mono- and divalent cations. In contrast, no definable microstructures were noted in the absence of cations [362],... 

Nederberg F, Bowden T, Hilbom J. Synthesis, characterization, and properties of phosphoryl choline functionalized poly e-caprolactone and charged phospholipid analogues. Macromolecules 2004 37 954-65. 

Choline occupies a key position between energy and protein metabolism. Two types of choline functions are known as choline per se, for which the choline moiety is required, and in the function of a methyl donor. Choline per se plays a major role in lipid metabolism, particularly in lipid transport, as lipotropic agent, but it is also an important source of labile methyl groups for the biosynthesis of other methylated compounds. Based on this second function, choline and methionine pathways partially overlap in providing methyl groups in a variety of reactions. Based on these assumptions we investigated the effects of rumen protected choline administration on milk production in dairy cows. To achieve this pourpose a meta-analysis was carried out to summarize available scientific evidence for the effect of oral rumen protected choline (RPC) supplementation in dairy cows. 

Acetylcholine Precursors. Early efforts to treat dementia using cholinomimetics focused on choline [62-49-7] (12) supplement therapy (Fig. 3). This therapy, analogous to L-dopa [59-92-7] therapy for Parkinson s disease, is based on the hypothesis that increasing the levels of choline in the brain bolsters acetylcholine (ACh) synthesis and thereby reverses deficits in cholinergic function. In addition, because choline is a precursor of phosphatidylcholine as well as ACh, its supplementation may be neuroprotective in conditions of choline deficit (104). 

Naturally occurring quaternary ammonium compounds have been reviewed (179). Many types of aliphatic, heterocycHc, and aromatic derived quaternary ammonium compounds are produced both in plants and invertebrates. Examples include thiamine (vitamin B ) (4) (see Vitamins) choline (qv) [62-49-7] (5) and acetylcholine (6). These have numerous biochemical functions. Several quaternaries are precursors for active metaboUtes. 

In nutrition, the most important function of choline appears to be the formation of lecithin (phosphatidylcholine) (2) and other cb oline-containing pho sphohpids. 

Choline Chloride. This compound [67-48-17 is a crystalline dehquescent salt, usually with a slight odor of trimethyl amine (6). It is very soluble in water, freely soluble in alcohol, slightly soluble in acetone and chloroform, and practically insoluble in ether, benzene, and ligroin. Its aqueous solutions ate neutral to litmus and are stable (4). The specific gravity of these solutions is a straight-line function between pure water and the value of 1.10 for the 80% solution, which represents the approximate limit of solubiUty. Choline chloride absorbs moisture from the atmosphere at relative humidities greater than 20% at 25.5°C. 

One important phospholipid is phosphatidylcholine, also called lecithin. Phosphatidylcholine is a mixture of diesters of phosphoric acid. One estei function is derived from a diacylglycerol, whereas the other is a choline [—OCH2CH2N(CH3)3] unit. 

Therapeutic Function Smooth muscle relaxant Chemical Name Theophylline cholinate Common Name Oxotriphylline oxytrimethylline... 

Acetylcholine (Ach) is an ester of acetic acid and choline with the chemical formula CH3COOCH2CH2N+ (CH3)3. ACh functions as a chemical transmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in a wide range of organisms, humans included. Neurotransmitter involved in behavioral state control, postural tone, cognition and memory, and autonomous parasympathetic (and preganglionic sympathetic) nervous system. 

All Kir channels are tetrameric proteins (see Fig. 3) of one-pore/two-transmembrane (1P/2TM) domain subunits which equally contribute to the formation of highly selective K+ channels. Most Kir channels can be assembled in functional homotetramers while some require heteromeric assembly (see Fig. 3). For example, functional GIRK channels underlying DCAch (Acetyl-choline-activated) current in atria are heteromultimers of two members ofKir3 subfamily Kir3.1 andKir3.4. 

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). 

The open channel has in most cases a selective permeability, allowing a restricted class of ions to flow,for example Na+, K+, Ca++ or Cl- and, accordingly, these channels are called Na+-channels, K+-channels, Ca -channels and Cr-channels. In contrast, cation-permeable channels with little selectivity reject all anions but discriminate little among small cations. Little is known about the structures and functions of these non-selective cation channels [1], and so far only one of them, the nicotinic acetylcholine receptor (nAChR, see Nicotinic Receptors), has been characterized in depth [2, 3]. The nAChR is a ligand-gated channel (see below) that does not select well among cations the channel is even permeable to choline, glycine ethylester and tris buffer cations. A number of other plasma... 

NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION CHOLINE 0 ACETYL-CoA... 

Low concentrations of solubilised jS-albumin inhibit ACh release in slices from rat hippocampus and cortex areas which show degeneration in AzD, but not in slices from the striatum which is unaffected. While not totally specific to ACh, since some inhibition of NA and DA and potentiation of glutamate release have been reported, this effect is achieved at concentrations of A/i below those generally neurotoxic. Since jS-amyloid can inhibit choline uptake it is also possible (see Auld, Kar and Quiron 1998) that in order to obtain sufficient choline for ACh synthesis and the continued function of cholinergic neurons, a breakdown of membrane phosphatidyl choline is required leading to cell death (so-called autocannibalism), /i-amyloid can also reduce the secondary effects of Mi receptor activation such as GTPase activity... 

Primarily using isolated plasma membrane vesicles as an experimental preparation, the functional properties of Na /H exchangers have been elucidated. The important kinetic properties include (1) stoichiometry (one-for-one) (2) reversibility (3) substrate specificity (monovalent cations Na, H, Li, NH4, but not K, Rb, Cs, choline) (4) modes of operation (Na -for-H, Na -for-Na Li " -for-Na, Na -for-NH4 ) (5) existence of an internal site for allosteric activation by (6) reversible inhibition by amiloride (Af-amidino-5-amino-6-chloropyr-azine carboxamide) and its 5-amino-substituted analogs and (7) competitive nature... 

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... 

Normal lungs, however, produce a chemical substance referred to as pulmonary surfactant. Made by alveolar type II cells within the alveoli, surfactant is a complex mixture of proteins (10 to 15%) and phospholipids (85 to 90%), including dipalmitoyl phosphatidyl choline, the predominant constituent. By interspersing throughout the fluid lining the alveoli, surfactant disrupts the cohesive forces between the water molecules. As a result, pulmonary surfactant has three major functions ... 

Acetylcholine synthesis and neurotransmission requires normal functioning of two active transport mechanisms. Choline acetyltransferase (ChAT) is the enzyme responsible for ACh synthesis from the precursor molecules acetyl coenzyme A and choline. ChAT is the neurochemical phenotype used to define cholinergic neurons although ChAT is present in cell bodies, it is concentrated in cholinergic terminals. The ability of ChAT to produce ACh is critically dependent on an adequate level of choline. Cholinergic neurons possess a high-affinity choline uptake mechanism referred to as the choline transporter (ChT in Fig. 5.1). The choline transporter can be blocked by the molecule hemicholinium-3. Blockade of the choline transporter by hemicholinium-3 decreases ACh release,... 

Another observation on oxalate formation is that other a-keto acids, such as oxalosuccinic acid (74) and a-ketoglutaric acid (106) do not seem to yield oxalate directly but indirectly (123). This appears to be due to the fact that only oxaloacetic acid can function as an acetate donor. In this connection the intervention of Coenzyme A may be considered, since it is reported to function in the acetylation of sulfanilamide and choline (73) and recently was shown to take part in the enzymatic synthesis of citric acid. This concept may be illustrated as follows ... 

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