One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health

Abstract

One carbon metabolism or methyl transfer, a crucial component of metabolism in all cells and tissues, supports the critical function of synthesis of purines, thymidylate and methylation via multiple methyl transferases driven by the ubiquitous methyl donor s-adenosylmethionine. Serine is the primary methyl donor to the one carbon pool. Intracellular folates and methionine metabolism are the critical components of one carbon transfer. Methionine metabolism requires vitamin B12, B6 as cofactors and is modulated by endocrine signals and is responsive to nutrient intake. Perturbations in one carbon transfer can have profound effects on cell proliferation, growth and function. Epidemiological studies in humans and experimental model have established a strong relationship between impaired fetal growth and the immediate and long term consequences to the health of the offspring. It is speculated that during development, maternal environmental and nutrient influences by their effects on one carbon transfer can impact the health of the mother, impair growth and reprogram metabolism of the fetus, and cause long term morbidity in the offspring. The potential for such effects is underscored by the unique responses in methionine metabolism in the human mother during pregnancy, the absence of transsulfuration activity in the fetus, ontogeny of methionine metabolism in the placenta and the unique metabolism of serine and glycine in the fetus. Dietary protein restriction in animals and marginal protein intake in humans causes characteristic changes in one carbon metabolism. The impact of perturbations in one carbon metabolism on the health of the mother during pregnancy, on fetal growth and the neonate are discussed and their possible mechanism explored.

Role of Cytosolic Serine Hydroxymethyl Transferase 1 (SHMT1) in Phosphate-Induced Vascular Smooth Muscle Cell Calcification

“…Reverse transcription of total RNA was performed using oligo(dT) [12][13][14][15][16][17][18] The specificity of the PCR products was confirmed by analysis of the melting curves. All PCRs were performed in duplicate and relative mRNA expression was calculated by using the 2 -ΔΔCt method with GAPDH as housekeeping gene.…”

“…One carbon transfer is a key component in amino acid and nucleotide synthesis as well as methylation of proteins, DNA and RNA [18,19] and, thus, participating in the regulation of cell function, proliferation and growth [18,20]. SHMT1 has been associated with apoptotic pathways [21].…”

“…SHMT1 has been associated with apoptotic pathways [21]. SHMT1 differs in targets and effects from the mitochondrial isoform SHMT2 [14,15,18]. Polymorphisms in the SHMT1 gene are associated with increased risk of cardiovascular disease [22,23] including ischemic stroke [24].…”

Pyridoxine (Vitamin B6) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation

“…This suggests that, under oxidative stress conditions, the feedback of ROS stimulates CBS, directing Se-homocysteine to transsulfuration, whereas it would affect remethylation by reducing MTR activity. According to Kalhan [2], alterations to the metabolism of one-carbon may be the main cause of impaired fetal growth. Additionally, because the transsulfuration pathway is interrupted at Se-cystathionine, large amounts of this metabolite could possibly accumulate with negative effects in embryos from OSe supplemented dams.…”

“…Additionally, during the demethylation of (Se) methionine to (Se) homocysteine, the universal bioactive methyl donor S-adenosylmethionine (SAM) is synthesized and donates its methyl group to a large number of methyl acceptors catalyzed by methyltransferases [1,2] with profound impacts on DNA synthesis, protection and repair, cellular metabolism, and cell proliferation and, consequently, with direct effects on embryo/fetal growth [3,4]. …”