Editing Choline (section)

=== Biosynthesis ===
[[File:Choline biosynthesis.svg|thumb|450px|class=skin-invert-image|[[Biosynthesis]] of choline in plants]]

In plants, the first step in [[de novo synthesis|''de novo'' biosynthesis]] of choline is the [[decarboxylation]] of [[serine]] into [[ethanolamine]], which is catalyzed by a [[decarboxylase|serine decarboxylase]].<ref name="pmid11461929">{{cite journal | vauthors = Rontein D, Nishida I, Tashiro G, Yoshioka K, Wu WI, Voelker DR, Basset G, Hanson AD | title = Plants synthesize ethanolamine by direct decarboxylation of serine using a pyridoxal phosphate enzyme | journal = The Journal of Biological Chemistry | volume = 276 | issue = 38 | pages = 35523–9 | date = September 2001 | pmid = 11461929 | doi = 10.1074/jbc.M106038200 | doi-access = free }}</ref> The synthesis of choline from ethanolamine may take place in three parallel pathways, where three consecutive ''N''-methylation steps catalyzed by a [[methyl transferase]] are carried out on either the free-base,<ref name="pmid16653153">{{cite journal | vauthors = Prud'homme MP, Moore TS | title = Phosphatidylcholine synthesis in castor bean endosperm : free bases as intermediates | journal = Plant Physiology | volume = 100 | issue = 3 | pages = 1527–35 | date = November 1992 | pmid = 16653153 | pmc = 1075815 | doi = 10.1104/pp.100.3.1527 }}</ref> phospho-bases,<ref name="pmid10799484">{{cite journal | vauthors = Nuccio ML, Ziemak MJ, Henry SA, Weretilnyk EA, Hanson AD | title = cDNA cloning of phosphoethanolamine ''N''-methyltransferase from spinach by complementation in ''Schizosaccharomyces pombe'' and characterization of the recombinant enzyme | journal = The Journal of Biological Chemistry | volume = 275 | issue = 19 | pages = 14095–101 | date = May 2000 | pmid = 10799484 | doi = 10.1074/jbc.275.19.14095 | doi-access = free }}</ref> or phosphatidyl-bases.<ref name="pmid11481443">{{cite journal | vauthors = McNeil SD, Nuccio ML, Ziemak MJ, Hanson AD | title = Enhanced synthesis of choline and glycine betaine in transgenic tobacco plants that overexpress phosphoethanolamine N-methyltransferase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 17 | pages = 10001–5 | date = August 2001 | pmid = 11481443 | pmc = 55567 | doi = 10.1073/pnas.171228998 | bibcode = 2001PNAS...9810001M | doi-access = free }}</ref> The source of the methyl group is [[S-adenosyl-L-methionine|''S''-adenosyl-{{sc|L}}-methionine]] and [[S-adenosyl-L-homocysteine|''S''-adenosyl-{{sc|L}}-homocysteine]] is generated as a side product.<ref>{{cite web | title = Superpathway of choline biosynthesis | url = https://biocyc.org/META/NEW-IMAGE?object=PWY-4762 | work = BioCyc Database Collection: MetaCyc | publisher = SRI International }}</ref>

[[File:Choline metabolism.svg|thumb|300px|class=skin-invert-image|Main pathways of choline (Chol) metabolism, synthesis and excretion. Click for details. Some of the abbreviations are used in this section.]]

In humans and most other animals, de novo synthesis of choline proceeds via the [[phosphatidylethanolamine N-methyltransferase]] (PEMT) pathway,<ref name=eu/> but biosynthesis is not enough to meet human requirements.<ref name=his/> In the hepatic PEMT route, [[3-phosphoglycerate]] (3PG) receives 2 [[acyl group]]s from [[acyl-CoA]] forming a [[phosphatidic acid]]. It reacts with [[cytidine triphosphate]] to form cytidine diphosphate-diacylglycerol. Its [[hydroxyl group]] reacts with serine to form [[phosphatidylserine]] which [[decarboxylate]]s to ethanolamine and [[phosphatidylethanolamine]] (PE) forms. A PEMT enzyme moves three [[methyl]] groups from three [[S-adenosyl methionine|''S''-adenosyl methionines]] (SAM) donors to the ethanolamine group of the phosphatidylethanolamine to form choline in the form of a phosphatidylcholine. Three [[S-adenosyl homocysteine|''S''-adenosylhomocysteines]] (SAHs) are formed as a byproduct.<ref name=eu/>

Choline can also be released from more complex precursors. For example, [[phosphatidylcholine]]s (PC) can be hydrolyzed to choline (Chol) in most cell types. Choline can also be produced by the CDP-choline route, [[cytosolic]] [[choline kinase]]s (CK) phosphorylate choline with [[Adenosine triphosphate|ATP]] to [[phosphocholine]] (PChol).<ref name=ze/> This happens in some cell types like liver and kidney. [[Choline-phosphate cytidylyltransferase]]s (CPCT) transform PChol to [[CDP-choline]] (CDP-Chol) with cytidine triphosphate (CTP). CDP-choline and [[diglyceride]] are transformed to PC by [[diacylglycerol cholinephosphotransferase]] (CPT).<ref name=eu/>

In humans, certain PEMT-enzyme [[mutation]]s and [[estrogen deficiency]] (often due to [[menopause]]) increase the dietary need for choline. In rodents, 70% of phosphatidylcholines are formed via the PEMT route and only 30% via the CDP-choline route.<ref name=eu/> In [[knockout mice]], PEMT inactivation makes them completely dependent on dietary choline.<ref name=ze/>