Choline accumulation

Jope RS, Jenden DJ, Ehrlich BE, et al Choline accumulates in erythrocytes during lithium therapy. N Engl J Med 299 833-834, 1978 Jope RS, Jenden DJ, Ehrlich BE, et al Erythrocyte choline concentrations are elevated in manic patients. Proc Natl Acad Sci USA 77 6144-6146, 1980 Jope RS, Morrisett RA, Snead OC Characterization of lithium potentiation of pilocarpine induced status epilepticus in rats. Exp Neurol 91 471-480, 1986 Jordan D, Spyer KM Brainstem integration of cardiovascular and pulmonary afferent activity. Prog Brain Res 67 295-314, 1986... 

In addition to battlefield trauma, there is also the risk of exposure to chemical weapons such as the nerve agents, notably the organophosphorus gases (soman, sarin, VX, tabun) [6]. Organophosphorus toxicity arises largely from their ability to irreversibly inhibit acetyl-cholinesterases, leading to effects associated with peripheral acetyl-choline accumulation (muscarinic syndrome) such as meiosis, profuse sweating, bradychardia, bronchioconstriction, hypotension, and diarrhoea. Central nervous system effects include anxiety, restlessness, confusion, ataxia, tremors. 

Veals, J. (1979) Effects of adrenocorticotropic hormone on 14C-choline accumulation and C-radioactivity release by brain synaptosomes. New York University, New York, PhD. thesis. 

The regulation of intracellular choline accumulation may contribute to steady the survival of ChR and induce changes in lipid composition which favour suspension growth at cool temperature. 

Fig. 1 Choline accumulation in Tobacco cells grown on 10 mM choline chloride.

Slow-channel syndrome. Abnormally long-lived openings of mutant AChR channels result in prolonged endplate currents and potentials, which in turn elicit one or more repetitive muscle action potentials of lower amplitude that decrement. The morphologic consequences stem from prolonged activation of the AChR channel that causes cationic overload of the postsynaptic region - the endplate myopathy - with Ca2+ accumulation, destruction of the junctional folds, nuclear apoptosis, and vacuolar degeneration of the terminal. Some slow-channel mutations in the transmembrane domain of the AChR render the channel leaky by stabilization of the open state, which is populated even in the absence of ACh. Curiously, some slow-channel mutants can be opened by choline even at the concentrations that are normally present in serum. Quinidine, an open-channel blocker of the AchR, is used for therapy. 

The effect of Li+ upon the synthesis and release of acetylcholine in the brain is equivocal Li+ is reported to both inhibit and stimulate the synthesis of acetylcholine (reviewed by Wood et al. [162]). Li+ appears to have no effect on acetyl cholinesterase, the enzyme which catalyzes the hydrolysis of acetylcholine [163]. It has also been observed that the number of acetylcholine receptors in skeletal muscle is decreased by Li+ [164]. In the erythrocytes of patients on Li+, the concentration of choline is at least 10-fold higher than normal and the transport of choline is reduced [165] the effect of Li+ on choline transport in other cells is not known. A Li+-induced inhibition of either choline transport and/or the synthesis of acetylcholine could be responsible for the observed accumulation of choline in erythrocytes. This choline is probably derived from membrane phosphatidylcholine which is reportedly decreased in patients on Li+ [166],... 

The question therefore arose about the fate of the methyl group from methionine. When minimal amounts of methionine were used to supplement the diet of rats given homocysteine as their main source of sulfur, the rats did not usually thrive, and at death had fatty accumulations in their livers. Best and his co-workers had earlier reported the efficacy of choline as a lipotropic agent, facilitating the mobilization of fat from the liver. Du Vigneaud therefore tried supplementing homcys-... 

Ginkgo alters lipid metabolism created by electroconvulsive shock treatments. EGb 761 reduced accumulation of free fatty acids and removal of diacylglycerol, which is more pronounced in the hippocampus than cerebral cortex (Rodriguez de Turco et al. 1993). Ginkgo also has protective effects on lipid membranes under hypoxic conditions. Bilobalide, but not ginkgolides, suppressed hydrolysis of choline induced... 

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

Fate of the remaining chylomicron components After most of tt triacylglycerol has been removed, the chylomicron remnan (which contain cholesteryl esters, phospholipids, apolipoprotein and some triacylglycerol) bind to receptors on the liver (seej 228) and are then endocytosed. The remnants are the hydrolyzed to their component parts. Cholesterol and the nitrogf nous bases of phopholipids (for example, choline) can be req cled by the body. [Note If removal of chylomicron remnants by th liver is defective, they accumulate in the plasma. This is seen i type III hyperlipoproteinemia (also called familial dysbetalipopro teinemia, see p. 229). 

Sinapoyl esters are phenolic compounds found in members of the Brassicaceae, which includes the model plant Arabidopsis thaliana. The two major sinapoyl esters are sinapoyl malate (3.92) and sinapoyl choline (3.93), which accumulate in leaves and seeds, respectively. Sinapoylmalate plays a role in the protection against UV-radiation (Landry et al., 1995), whereas sinapoyl choline may be used as a storage form of choline in seeds (Shirley and Chappie, 2003). The precursor of these two esters is sinapate (3.35). 

Standard treatment for OPP poisoning is i.v. injection with atropine sulfate to protect the muscarinic end-organs from the accumulation of excessive acetyl choline concentrations. Diagnostic testing, or treatment with atropine must be used cautiously in patients with glaucoma, in view of the risk of increased intraocular pressure from the drug. 

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