FIGURE 1.

Metabolic pathway of intravenously administered choline and its methyl groups using deuterium-labeled methyl-D₉-choline. Methyl groups labeled with deuterium are represented by the black dots; the unlabeled methyl groups are represented by the white dots. The methyl-D₉-choline can enter the CDP-choline pathway (*) to produce D₉-PC. Alternatively, it can be oxidized to D₉-betaine, which then donates a single methyl group to homocysteine, producing D₆-DMG and D₃-methionine. D₃-methionine serves as a precursor for D₃-SAMe, which can be used by PEMT (‡) to sequentially methylate PE, forming D₃-PC as well as smaller amounts of D₆-PC. A fraction of D₃-choline or D₆-choline is released by hydrolysis of PEMT-derived D₃-PC or D₆-PC in the liver and recycled back to D₃-PC or D₆-PC by the CDP-choline pathway. CDP-choline, cytidine diphosphocholine; DMG, dimethylglycine; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PEMT, phosphatidylethanolamine N-methyltransferase; S-AdHo, S-adenosylhomocysteine; SAMe, S-adenosylmethionine.