Abstract

Choline and glycine are inter-related through their roles in methyl metabolism. Choline is metabolized to betaine, which donates a methyl group to homocysteine to form methionine, also generating dimethylglycine, which is further metabolized to glycine. Choline is transported across the placenta and is higher in fetal than maternal plasma. Placental glycine transfer, however, is limited and poor glycine status has been suggested in preterm infants. Insufficient glycine for glutathione (GSH) synthesis results in increased metabolism of gamma-glutamyl cysteine to 5-oxoproline. We measured plasma 5-oxoproline as a metabolic indicator to address whether choline, via dimethylglycine, contributes physiologically relevant amounts of glycine in pregnancy. Blood was collected from healthy term pregnant women and their newborn infants at delivery (n = 46) and nonpregnant healthy women (n = 19) as a reference group. Plasma choline, betaine, dimethylglycine, homocysteine, methionine, and 5-oxoproline were quantified by HPLC-tandem MS. Plasma choline was 45% higher, but betaine was 63% lower and dimethylglycine was 28% lower in pregnant than nonpregnant women (P < 0.01). Higher white blood cell choline dehydrogenase messenger RNA levels in a random subset of pregnant (n = 8) than nonpregnant women (n = 7) (P < 0.01) suggest increased betaine and dimethylglycine turnover rather than decreased synthesis. Plasma choline, betaine, and dimethylglycine were higher (P < 0.001) in fetal plasma (36.4 +/- 13, 29.4 +/- 1.0, and 2.44 +/- 0.12 micromol/L, respectively) than maternal plasma (15.3 +/- 0.42, 14.1 +/- 0.6 and 1.81 +/- 0.12 micromol/L, respectively). Concentrations of 5-oxoproline and dimethylglycine were inversely (P < 0.05) correlated in maternal (Spearman rho = -0.35) and fetal plasma (Spearman rho = -0.32), suggesting that choline, via dimethylglycine, contributes glycine for GSH synthesis in human development.