title: Formate metabolism in fetal and neonatal sheep.
abstract: By virtue of its role in nucleotide synthesis, as well as the provision of methyl groups for vital methylation reactions, one-carbon metabolism plays a crucial role in growth and development. Formate, a critical albeit neglected component of one-carbon metabolism, occurs extracellularly and may provide insights into cellular events. We examined formate metabolism in chronically cannulated fetal sheep (gestation days 119-121, equivalent to mid-third trimester in humans) and in their mothers as well as in normal full-term lambs. Plasma formate levels were much higher in fetal lamb plasma and in amniotic fluid (191 ± 62 and 296 ± 154 μM, respectively) than in maternal plasma (33 ± 13 μM). Measurements of folate, vitamin B12, and homocysteine showed that these high formate levels could not be due to vitamin deficiencies. Elevated formate levels were also found in newborn lambs and persisted to about 8 wk of age. Formate was also found in sheep milk. Potential precursors of one-carbon groups were also measured in fetal and maternal plasma and in amniotic fluid. There were very high concentrations of serine in the fetus (∼1.6 mM in plasma and 3.5 mM in the amniotic fluid) compared with maternal plasma (0.19 mM), suggesting increased production of formate; however, we cannot rule out decreased formate utilization. Dimethylglycine, a choline metabolite, was also 30 times higher in the fetus than in the mother.
authors: Department of Veterinary Physiology and Pharmacology and Michael DeBakey Institute, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, College Station, Texas;
authors: Shannon E
authors: SE
authors: Washburn
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York;
authors: Marie A
authors: MA
authors: Caudill
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York;
authors: Olga
authors: O
authors: Malysheva
authors: Nutrition Research Division, Health Canada, Ottawa, Ontario, Canada; and.
authors: Amanda J
authors: AJ
authors: MacFarlane
authors: Nutrition Research Division, Health Canada, Ottawa, Ontario, Canada; and.
authors: Nathalie A
authors: NA
authors: Behan
authors: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors: Brian
authors: B
authors: Harnett
authors: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors: Luke
authors: L
authors: MacMillan
authors: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors: Theerawat
authors: T
authors: Pongnopparat
authors: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada jbrosnan@mun.ca.
authors: John T
authors: JT
authors: Brosnan
authors: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors: Margaret E
authors: ME
authors: Brosnan
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism; D005561:Formates / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood; D049590:Postpartum Period / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood; D012756:Sheep / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D005561:Formates; D006710:Homocysteine; C030544:formic acid; D005492:Folic Acid; D014805:Vitamin B 12
keywords: folate; milk; mitochondria; one-carbon metabolism; serine; vitamin B12