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About two thirds of the phosphatidylcholine (PC) is produced from choline via the phosphorylation (Kennedy) pathway and about one third is oxidized to betaine which then enters the PEMT pathway resulting in the methylation of phosphoethanolamine by the PEMT (phosphoethanolamine methyl transferase) to form phosphatidylcholine. It is the PC that is formed by the PEMT pathway that is capable of binding the long chain fatty acids arachadonic acid and DHA, and NOT the PC synthesized from the Kennedy pathway. Hence the PEMT gene is critical for DHA incorporation into the phospholipid to form PC-DHA which is then transported in blood, across the placenta and also into the brain.

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November 12, 2020
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Phosphatidylcholine: A Key Source of DHA

Phosphatidylcholine (PC) refers to a family of molecules containing glycerol, phosphocholine, and 2 fatty acids. The fatty acids in PC can substantially differ, leading to an array of different PCs with the potential for different roles in the body. Recently, PCs have been identified as a critical carrier of the omega 3 fatty acid, docosahexaenoic acid (DHA) in the blood.

Mice lacking the gene,​ PEMT,​ a prominent methyl-transferring enzyme required for one pathway of PC synthesis in the liver, exhibit substantially reduced levels of DHA in the blood​ (Watkins, Zhu and Zeisel, 2003; Forman, 2005; Lazar, 2017)​. Furthermore, mice born to mothers lacking ​PEMT exhibit reduced DHA accumulation in the brain​ (da Costa ​et al.,​ 2010)​, linking PC synthesis in the mother’s liver to the supply of a key nutrient for fetal neuronal development.

Importantly, a lack of adequate methyl donor nutrients, such as choline, or genetic variants that impact the activity of PEMT, can then influence the amount of DHA circulating in the blood to be taken up by tissues ​(da Costa ​et al.,​ 2011)​ - an effect that is likely pronounced during pregnancy, during which PEMT activity typically increases dramatically in response to estrogen. Few studies of DHA supplementation, especially the large literature base in pregnancy, have adequately considered the influence of choline intake, or the impact of common genetic variants in PEMT, on their results.

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Who Wrote This X Fact
Kevin C. Klatt PhD RD
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Kevin C. Klatt, PhD, RD, is a postdoctoral fellow at the Baylor College of Medicine. Kevin received his PhD in Molecular Nutrition from Cornell University and completed his dietetic internship at the National Institutes of Health Clinical Center. Kevin’s research aims to better characterize nutrient-x-gene interactions and their impact on physiology and disease risk, using in vitro and animal model systems, as well as human intervention and controlled feeding trials. Kevin is the Inaugural Dennis M.Bier Young Career Editor at the American Journal of Clinical Nutrition and is an active member of the executive committee of the Research Dietetics Practice Group of the Academy of Nutrition and Dietetics.

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