Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Department of Nutritional Science, University of Toronto, Toronto, Ontario, Canada.
Am J Clin Nutr. 2019 Nov 1;110(5):1131-1137. doi: 10.1093/ajcn/nqz152.
One-carbon metabolism, responsible for purine and thymidylate synthesis and transmethylation reactions, plays a critical role in embryonic and fetal development. Formate is a key player in one-carbon metabolism. In contrast to other one-carbon metabolites, it is not linked to tetrahydrofolate, is present in plasma at appreciable concentrations, and may therefore be distributed to different tissues.
The study was designed to determine the concentration of formate in cord blood in comparison with maternal blood taken earlier in pregnancy and at delivery and to relate formate concentrations to potential precursors and key fetal genotypes.
Formate and amino acids were measured in plasma during early pregnancy (12-16 wk), at delivery (37-42 wk), and in cord blood samples from 215 mothers, of a prospective cohort study. Three fetal genetic variants in one-carbon metabolism were assessed for their association with cord plasma concentrations of formate.
The formate concentration was ∼60% higher in the cord blood samples than in mothers' plasma. The maternal formate concentrations did not differ between the early pregnancy samples and those taken at delivery. Plasma concentrations of 4 formate precursors (serine, glycine, tryptophan, and methionine) were increased in cord blood compared with the maternal samples. Cord blood formate was influenced by fetal genotype, being ∼12% higher in infants harboring the MTHFR A1298C (rs1801131) AC or CC genotypes and 10% lower in infants harboring the MTHFD1 G1958A (rs2236225) GA or AA genotypes.
The increased formate concentrations in cord blood may support the increased activity of one-carbon metabolism in infants. As such, it would support increased rates of purine and thymidylate synthesis and the provision of methionine for methylation reactions.
一碳代谢负责嘌呤和胸苷酸的合成以及转甲基反应，对胚胎和胎儿发育起着至关重要的作用。甲酸盐是一碳代谢中的关键物质。与其他一碳代谢物不同，它与四氢叶酸没有联系，在血浆中以可观的浓度存在，因此可能分布到不同的组织中。
本研究旨在比较脐带血中甲酸盐的浓度与妊娠早期、分娩时采集的母体血液中甲酸盐的浓度，并将甲酸盐浓度与潜在的前体物质和关键的胎儿基因型相关联。
在一项前瞻性队列研究中，对 215 位母亲的血浆样本进行了早期妊娠（12-16 周）、分娩时（37-42 周）和脐带血样本的测量，包括甲酸盐和氨基酸。评估了三种一碳代谢中的胎儿遗传变异与脐带血浆中甲酸盐浓度的关系。
脐带血样本中甲酸盐的浓度比母体血浆中甲酸盐的浓度高约 60%。早期妊娠样本和分娩时样本的母体甲酸盐浓度没有差异。与母体样本相比，脐带血中 4 种甲酸盐前体物质（丝氨酸、甘氨酸、色氨酸和蛋氨酸）的浓度增加。脐带血中甲酸盐受胎儿基因型的影响，携带 MTHFR A1298C（rs1801131）AC 或 CC 基因型的婴儿中甲酸盐的浓度增加约 12%，携带 MTHFD1 G1958A（rs2236225）GA 或 AA 基因型的婴儿中甲酸盐的浓度降低约 10%。
脐带血中甲酸盐浓度的增加可能支持婴儿一碳代谢活性的增加。因此，它将支持嘌呤和胸苷酸合成的增加率，并为甲基化反应提供蛋氨酸。
