Phosphatidylcholine containing docosahexaenoic acid (DHA) as a marker for in vivo phospatidylethanolamine methyltransferase: implications for brain development

Abstract

Phosphatidylethanolamine methyltransferase (PEMT), which sequentially methylates phosphatidylethanolamine to phosphatidylcholine (PtdCho), is the body’s only pathway for de novo synthesis of choline. Mice lacking functional PEMT (PEMT −/−) quickly become choline deficient and require dietary choline for survival. PEMT −/− mice also have a substantial loss of PtdCho-DHA in liver and plasma, regardless of dietary choline intake. Therefore, we propose plasma PtdCho-DHA to be a useful, non-invasive marker of in vivo PEMT activity in humans. To test this, we used gas chromatography to measure PtdCho-DHA in plasma samples obtained from adult men and women as well as in primary human hepatocytes. PEMT activity using [3H]S-adenosylmethionine (a substrate for PEMT) was also measured in the hepatocytes. To date, plasma PtdCho-DHA was elevated in pre-menopausal women as compared to post-menopausal women and men, consistent with the ability of estrogen to induce PEMT (p<0.01). Furthermore, women with a single nucleotide polymorphism (SNP) in the PEMT gene that possibly decreases PEMT expression were found to have correspondingly less plasma PtdCho-DHA (p<0.05). With corresponding data in hepatocytes, PtdCho-DHA shows promise as a marker of in vivo PEMT activity in humans and could help with identifying individuals that may be at risk of choline deficiency. A deficiency in PEMT has also been shown to alter brain development in mice and loss of PtdCho-DHA may be partially responsible for these effects. Ongoing investigations explore the importance of PtdCho-DHA in fetal brain development.