Biological Methylation and Drug Design pp 101-110 | Cite as
Brain Phosphatidylcholine Pools as Possible Sources of Free Choline for Acetylcholine Synthesis
Abstract
Choline in cholinergic neurons has two fates: it is a constituent of phosphatidylcholine (PC) and other phospholipids (sphingomyelin, choline plasmalogens, lysophosphatidylcholine) and is used as a precursor for synthesis of a neurotransmitter, acetylcholine (ACh). The pool of PC in the brain (about 16 µmol/g tissue) is several orders of magnitude larger than the pools of free choline and ACh. A number of experimental observations support the hypothesis that at least a portion of this lipid-bound choline can provide free choline for ACh formation. Firstly, more choline molecules leave the brain than enter it (i.e., there is a negative arteriovenous difference) (Dross & Kewitz, 1972; Aquilonius et al., 1975; Choi et al., 1975; Spanner et al., 1976), even though lipid-bound circulating PC apparently does not enter the brain (Pardridge et al., 1979), indicating that brain cells both produce choline-containing compounds (like PC) de novo, and liberate free choline from these larger molecules. Secondly, when labelled choline was infused intravenously into rats, specific radioactivities of free choline in the brain were found to be lower than those in the blood or liver, suggesting that unlabelled choline, produced within the brain, was diluting the material taken up from the blood (Choi et al., 1975; Kewitz & Pleul, 1976; Spanner et al., 1976). Thirdly, consumption of a choline-deficient diet had no effect on the striatal levels of choline and ACh in rats, even though blood choline concentrations were markedly decreased (Millington & Wurtman, 1982).
Keywords
Unpublished Experiment Methylation Pathway Free Choline Acetylcholine Synthesis Choline PlasmalogensPreview
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