title: One-carbon metabolism, fetal growth and long-term consequences.
abstract: One-carbon metabolism, or methyl transfer, is critical for metabolism in all cells, is involved in the synthesis of purines, pyrimidines, in the methylation of numerous substrates, proteins, DNA and RNA, and in the expression of a number of genes. Serine is the primary endogenous methyl donor to the one carbon pool. Perturbations in methyl transfer due to nutrient and hormonal changes can have profound effect on cell function, growth and proliferation. It is postulated that at critical stages in development, nutrient and environmental influences by their effect on methyl transfer can impair fetal growth, reprogram metabolism and cause long-term morbidity in the offspring. The potential for their effects is underscored by the unique gestation-related changes in methyl transfer in healthy women, the late expression of transsulfuration cascade in the fetus and the unique metabolism of glycine and serine in the fetus. Dietary protein restriction in animal models and protein malnutrition in humans causes remarkable changes in the methyl transfer in vivo. Although the specific consequences of perturbation in maternal and fetal methyl transfer remain to be determined, a profound influence is suggested by the demonstrated relationship between maternal folate and B12 insufficiency and metabolic programming.
authors.affiliation: Department of Molecular Medicine, Cleveland Clinic, Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Satish C
authors.initials: SC
authors.lastname: Kalhan
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002244:Carbon / Q000378:metabolism*; D019175:DNA Methylation; D004044:Dietary Proteins / Q000008:administration & dosage; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009752:Nutritional Status; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D011488:Protein Deficiency / Q000150:complications* / Q000378:metabolism; D014804:Vitamin B Deficiency / Q000150:complications* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004044:Dietary Proteins; D002244:Carbon