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Is Choline Really Essential? (2)

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DE NOVO SYNTHESIS


Unlike vitamin C, which we cannot make from something else, choline can be de novo biosynthesized (produced in the body) from the sequential methylation of phosphatidylethanolamine. The enzyme phosphatidylethanolamine-N-methyltransferase (PEMT, as you’ll recall from your genetics studies) synthesizes phosphatidylcholine by methylating phosphatidylethanolamine using S-adenosylmethionine to donate methyl groups. The limiting factor is the availability of S-adenosylmethionine. If a person’s diet is rich in methionine, an amino acid found in superfluous quantities in meats, de novo synthesis can be done as a matter of course in most people lacking debilitating polymorphisms at the PEMT gene. Early studies estimated that 15-40% of phosphatidylcholine in the liver in routinely synthesized de novo through the PEMT enzyme[1].


DEMANDS OF METHYLATION


The speed at which a person can develop liva pathology like liver disease from choline deficiency depends on how heavy his body’s methylation demands are. Choline is used extensively in 1-carbon metabolism, called methylation. In the human body, homocysteine is recycled into methionine through a reaction catalyzed by betaine:homocysteine methyltransferase. The conversion of choline into its metabolite betaine makes available the three methyl groups of choline. The mitochondrial choline dehydrogenase enzyme converts choline into betaine aldehyde, which is then oxidized in the cytoplasm or mitochondria into the methyl-donor betaine.


As a diet becomes deficient in methionine, the demand on choline for methyl donors increases[2][3]. The demand on methyl donors is further affected by several genetic polymorphisms (and epigenetics[4]), including those at the MTHFR gene (C677T and A1298C), leading to greatly increased demand for choline in affected individuals[5]. Genetic polymorphisms aside, the Food and Nutrition Board of the Institute of Medicine describes an adequate dietary intake of choline at 550 mg/day for adult men and 425 mg/day for adult women[6].


To continue to the next blog post in this series, click here.

To return to an overview of the blog series on the cholinergic system, click here.

[1] Zeisel, S. H., Da Costa, K. A., Franklin, P. D., Alexander, E. A., Lamont, J. T., Sheard, N. F., & Beiser, A. (1991). Choline, an essential nutrient for humans. The FASEB journal, 5(7), 2093-2098. [2] Zeisel, S. H., Da Costa, K. A., Franklin, P. D., Alexander, E. A., Lamont, J. T., Sheard, N. F., & Beiser, A. (1991). Choline, an essential nutrient for humans. The FASEB journal, 5(7), 2093-2098. [3] Zeisel, S. H., & Blusztajn, J. K. (1994). Choline and human nutrition. Annual review of nutrition, 14(1), 269-296. [4] Zeisel, S. H. (2007). Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline. IUBMB life, 59(6), 380-387. [5] Kohlmeier, M., da Costa, K. A., Fischer, L. M., & Zeisel, S. H. (2005). Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proceedings of the National Academy of Sciences, 102(44), 16025-16030. [6] Zeisel, S. H., & Da Costa, K. A. (2009). Choline: an essential nutrient for public health. Nutrition reviews, 67(11), 615-623.

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