Unlike pregnant adult women, pregnant adolescent girls cannot maintain glycine flux during late pregnancy because of decreased synthesis from serine

Abstract

During pregnancy, glycine and serine become more important because they are the primary suppliers of methyl groups for the synthesis of fetal DNA, and more glycine is required for fetal collagen synthesis as pregnancy progresses. In an earlier study, we reported that glycine flux decreased by 39 % from the first to the third trimester in pregnant adolescent girls. As serine is a primary precursor for glycine synthesis, the objective of this study was to measure and compare glycine and serine fluxes and inter-conversions in pregnant adolescent girls and adult women in the first and third trimesters. Measurements were made after an overnight fast by continuous intravenous infusions of 2 H 2 -glycine and 15 N-serine in eleven adolescent girls (17·4 (SE 0·1) years of age) and in ten adult women (25·8 (SE 0·5) years of age) for 4 h. Adolescent girls had significantly slower glycine flux and they made less glycine from serine in the third (P < 0·05) than in the first trimester. Baby birth length was significantly shorter of adolescent girls (P = 0·04) and was significantly associated with third trimester glycine flux. These findings suggest that the pregnant adolescent cannot maintain glycine flux in late pregnancy compared with early pregnancy because of decreased synthesis from serine. It is possible that the inability to maintain glycine synthesis makes her fetus vulnerable to impaired cartilage synthesis, and thus linear growth.Key words: Pregnant adolescent girls: Pregnant adult women: Glycine: Serine Pregnancy during adolescence in Jamaica and elsewhere is associated with a high prevalence of low birth weight (1,2) . It has been proposed that this is due to an inability of the adolescent mother to provide the nutrient needs for her own growth and the growth of her fetus. In particular, the requirement for amino acids increases as pregnancy progresses in order to sustain increased rates of protein deposition (3) and to support increased availability of glucose through gluconeogenesis (4) .Dispensable amino acids comprise the bulk of maternal amino acids transferred to the fetus in pregnancy (5) . A good example is glycine, which is a provider of methyl groups needed for the synthesis of DNA necessary for cell division to support maternal and fetal tissue deposition (6,7) . In addition, most of fetal cartilage is synthesised during late pregnancy and glycine constitutes 25 % of the amino acids in cartilage (8) . Therefore, as pregnancy progresses, there is a higher fetal demand for glycine. From our earlier study, glycine flux decreased by 39 % from the first trimester to the third trimester in pregnant adolescent girls (9) . Plasma glycine concentration in pregnant adolescent girls also decreased significantly from trimester 1 to 3, indicating a reduced availability. These findings suggested that after an overnight fast pregnant adolescent girls had a shortage in glycine supply in late pregnancy because they could not maintain production similar to their adult counterparts. However, de novo synthesis of g...

Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study

“…However, there is evidence that glycine is relatively poorly transported across the human placenta and placental glycine supply is thought to be lower than fetal demand 36 . It has been hypothesized, and with some support from sheep and human pregnancy tracer studies, that maternal circulating serine is not transported to the fetal circulation via the placenta but is used within the utero-placental tissues to synthesize glycine, and via this mechanism makes an important contribution to fetal glycine supply 37,38 . Our findings appear to support this hypothesis, that is, a causal role of maternal circulating serine on offspring birthweight was found but little evidence on causal effects of maternal circulating glycine on offspring birthweight.…”

The Association of Maternal Age With Fetal Growth and Newborn Measures: The Mumbai Maternal Nutrition Project (MMNP)

“…For example, amino acid kinetics studies suggest that adolescents may be less able than older women to increase their circulating amino acid concentration through synthesis and/or protein breakdown in response to pregnancy. 22,23 This could reduce the availability of the amino acids to the fetus, especially in late pregnancy when requirements are greatest to support rapid fetal growth. This mechanism does not explain the findings in early pregnancy when fetal nutrient requirements are small.…”

Effects of insufficient serine on health and selenoprotein expression in rats and their offspring

“…Hypohomocysteinemic was found in pregnant rats fed 20C diet; serine deprivation increased plasma Hcy concentration but were still below the normal Hcy level. Protein requirements are higher in pregnant rats compared to those not pregnant ( 33 ). The possible mechanism is due to the preferential involvement of endogenous serine in selenoproteins synthesis when exogenous serine is absent.…”

“…Endogenous serine is produced not only by the glycolysis pathway, but also from the transformation of glycine. On the other hand, endogenously synthesized serine acts as a methyl donor for 5-MTHF in the folic acid cycle for the synthesis of SAM, and also for the methylation of excess selenium ( 33 ). Our previous result showed serine played a direct role in selenoprotein expression through the de novo biosynthesis of Sec-tRNA [Ser]Sec in vitro ( 2 ); this was also supported in vivo by other studies ( 34 , 35 ).…”