Sarita Devi ¹, Tinku Thomas ², Pratibha Dwarkanath ¹, Annamma Thomas ³, C. N. Sheela ³, Arpita Mukhopadhyay ¹, Anura V. Kurpad ¹

Affiliations
1 Division of Nutrition, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore-560 034, IN
2 Division of Epidemiology and Biostatistics Unit, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore-560 034, IN
3 Department of Obstetrics and Gynaecology, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore-560 034, IN

Abstract

Low intakes of quality dietary protein could affect the methionine cycle during pregnancy, which is important for fetal growth and epigenetic regulations. Since low quality protein intake is prevalent in India, it is important to define biomarkers of the low protein intake, specifically of methyl cycle homeostasis. A secondary analysis of data was performed, from a randomized intervention trial with 500 ml milk/d on south Indian pregnant women, to examine the association of dietary protein intake with concentrations of specific amino acids (methionine, glycine and serine). The subjects also underwent isotopic infusions (n = 52) for the measurement of amino acid kinetics. Dietary intakes were measured each week by multiple 24 h recall until delivery. The plasma concentrations of amino acids (methionine, serine and glycine) were compared with kinetics of methionine i.e. transmethylation, remethylation and transulfuration (TM, RM, TS) and serine to glycine conversion rates, as measured by stable isotope labeled amino acid infusion. Dietary protein intake in the 3^rd trimester correlated positively with intakes of milk and milk based food products (ρ=0.52, p<0.001) and methionine (ρ=0.97, p<0.001) and with gestational weight gain (GWG, ρ=0.32, p=0.044). While the methionine concentration did not correlate with methyl cycle flux parameters (TM, RM and TS), the plasma concentrations of conditionally essential serine and glycine were positively correlated with their respective flux rate and with RM, TM and TS rates. Further, glycine concentrations specifically correlated positively with serine to glycine conversion rates (ρ=0.32, p=0.027). Dietary protein and methionine supply are important for the conservation of methionine during pregnancy. This had an effect on GWG, but not on birth weight, though this may have been due to the relatively small sample size. The plasma concentration of glycine was correlated with the serine-glycine conversion, which affords methyl groups for the body and supplies these when dietary protein/methionine is in poor supply. This indicates that itcan act as a biomarker of the serine-glycine conversion flux rate, which increases in the presence of a poor protein supply. In general, the plasma concentrations of these conditionally essential amino acids may be biomarkers of the methyl cycle during pregnancy, but this needs to be tested in a larger sample.

Keywords

Amino Acid Kinetics, Maternal Protein Intake, Glycine, Serine, Methionine Cycle, Pregnancy.

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Sarita Devi ¹, Julian Crasta ², Tinku Thomas ³, Pratibha Dwarkanath ¹, Annamma Thomas ⁴, C. N. Sheela ⁴, Anura V. Kurpad ¹, Arpita Mukhopadhyay ¹

Affiliations
1 Division of Nutrition, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore-560 034, IN
2 Department of Pathology, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore-560 034, IN
3 Division of Epidemiology and Biostatistics Unit, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore-560 034, IN
4 Department of Obstetrics and Gynecology, St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore-560 034, IN

Abstract

Maternal intake of quality protein regulates placental development and function thereby affecting fetal growth. Considering the prevalence of inadequate intakes of quality protein in Indian pregnant women, understanding the interplay between maternal supply of protein, its metabolism and fetoplacental growth becomes important. A secondary analysis of data from an open labelled-randomized intervention trial with 500 ml milk/day on south Indian pregnant women with marginally low vitamin B₁₂ status, was performed to assess the relations between placental parameters and maternal trimester 3 methyl-cycle amino acid status as well as kinetics. This analysis was performed for 42 pregnancies from the trial where placentae had been collected and placental parameters had been measured. For these pregnancies, data on trimester 3 methionine, serine and glycine kinetics as well as plasma free amino acid concentrations were available. Protein intake and plasma citrulline concentrations were positively correlated at trimester 3 (ρ = 0.34, P = 0.027). Placental weight correlated positively with methyl-cycle specific amino acid concentrations [methionine (ρ = 0.32, P = 0.0388), serine (ρ = 0.49, P = 0.0009)], methionine kinetics [total methionine flux rates (ρ = 0.42, P = 0.006), RM (ρ = 0.45, P = 0.003), TS (ρ = 0.32, P = 0.046), TM (ρ = 0.45, P = 0.004)] and with birth weight (ρ = 0.57, P < 0.001). Findings from the current study indicate that maternal amino acid availability and more importantly, maternal methionine kinetics, positively influenced placental growth, likely mediated by key amino acids such as citrulline, which is known to regulate placental blood flow and function. As an appropriately functioning placenta is indispensable for fetal growth, these findings will form the basis for detailed mechanistic explorations into the placental regulation of maternal supply of amino acid to the fetus for designing effective intervention strategies towards optimizing fetomaternal health during and after pregnancy.

Keywords

Vitamin B₁₂, Pregnancy, Glycine, Methionine, Serine, Methionine Kinetic, Amino Acids.

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