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== Function == Choline and its derivatives have many biological functions. Notably choline serves as a precursor for other essential cell components and signaling molecules, such as phospholipids that form cell membranes, the [[neurotransmitter]] acetylcholine, and the [[osmoregulator]] [[trimethylglycine]] ([[betaine]]). Trimethylglycine in turn serves as a source of [[methyl group]]s by participating in the biosynthesis of [[S-adenosylmethionine|''S''-adenosylmethionine]].<ref>{{cite journal | vauthors = Glier MB, Green TJ, Devlin AM | title = Methyl nutrients, DNA methylation, and cardiovascular disease | journal = Molecular Nutrition & Food Research | volume = 58 | issue = 1 | pages = 172β82 | date = January 2014 | pmid = 23661599 | doi = 10.1002/mnfr.201200636 | doi-access = free }}</ref><ref name="pmid8333583">{{cite journal | vauthors = Barak AJ, Beckenhauer HC, Junnila M, Tuma DJ | title = Dietary betaine promotes generation of hepatic ''S''-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration | journal = Alcoholism: Clinical and Experimental Research | volume = 17 | issue = 3 | pages = 552β5 | date = June 1993 | pmid = 8333583 | doi = 10.1111/j.1530-0277.1993.tb00798.x}}</ref> === Phospholipid precursor === Choline is transformed to diverse phospholipids, like phosphatidylcholines and sphingomyelins.<ref name=lpi/><ref name=ods/> These are found in all cell membranes and the membranes of most cell organelles.<ref name=ze/> Phosphatidylcholines are structurally important part of the cell membranes. In humans, 40β50% of their phospholipids are phosphatidylcholines.<ref name=eu/> Choline phospholipids also form [[lipid rafts]] in the cell membranes along with [[cholesterol]].<ref name=lpi/> The rafts are centers, for example for [[cholinergic]] [[Receptor (biochemistry)|receptors]] and receptor [[signal transduction]] enzymes.<ref name=lpi/><ref name=ze/> Phosphatidylcholines are needed for the synthesis of [[VLDL]]s: 70β95% of their phospholipids are phosphatidylcholines in humans.<ref name=eu/> Choline is also needed for the synthesis of [[pulmonary surfactant]], which is a mixture consisting mostly of phosphatidylcholines. The surfactant is responsible for lung elasticity, that is for lung tissue's ability to contract and expand. For example, deficiency of phosphatidylcholines in the lung tissues has been linked to [[acute respiratory distress syndrome]].<ref>{{cite journal | vauthors = Dushianthan A, Cusack R, Grocott MP, Postle AD | title = Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome | journal = Journal of Lipid Research | volume = 59 | issue = 6 | pages = 1034β1045 | date = June 2018 | pmid = 29716960 | pmc = 5983399 | doi = 10.1194/jlr.P085050 |doi-access=free }}</ref> Phosphatidylcholines are excreted into [[bile]] and work together with [[bile acid]] salts as [[surfactant]]s in it, thus helping with the [[intestinal]] absorption of [[lipid]]s.<ref name=ze/> === Acetylcholine synthesis === Choline is a precursor to [[acetylcholine]], a neurotransmitter that plays a necessary role in [[muscle contraction]], memory and [[neural development]].<ref name=lpi/><ref name=ods/><ref name=eu/><ref name="Kenny2025"/> Nonetheless, there is little acetylcholine in the human body relative to other forms of choline.<ref name=ze/> Neurons also store choline in the form of phospholipids to their cell membranes for the production of acetylcholine.<ref name=eu/> === Source of trimethylglycine === In humans, choline is [[oxidized]] irreversibly in liver mitochondria to [[glycine betaine aldehyde]] by [[choline oxidase]]s. This is oxidized by mitochondrial or cytosolic [[betaine-aldehyde dehydrogenase]]s to trimethylglycine.<ref name=eu/> Trimethylglycine is a necessary osmoregulator. It also works as a substrate for the [[BHMT]]-enzyme, which methylates [[homocysteine]] to [[methionine]]. This is a ''S''-adenosylmethionine (SAM) precursor. SAM is a common reagent in biological [[methylation]] reactions. For example, it methylates [[guanidine]]s of [[DNA]] and certain [[lysine]]s of [[histone]]s. Thus it is part of [[gene expression]] and [[epigenetic regulation]]. Choline deficiency thus leads to elevated homocysteine levels and decreased SAM levels in blood.<ref name=eu/>
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