John T Brosnan1, Lesley Plumptre2,3, Margaret E Brosnan1, Theerawat Pongnopparat1, Shannon P Masih2,3, Carly E Visentin2,3, Howard Berger4, Yvonne Lamers5, Marie A Caudill6, Olga V Malysheva6, Deborah L O'Connor2,7, Young-In Kim2,3,8. 1. Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. 2. Department of Nutritional Science, University of Toronto, Toronto, Ontario, Canada. 3. Keenan Research Centre for Biomedical Sciences of St. Michael's Hospital, Toronto, Ontario, Canada. 4. Department of Obstetrics and Gynecology, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. 5. Food, Nutrition and Health, University of British Columbia, Vancouver, British Columbia, Canada. 6. Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA. 7. Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada. 8. Division of Gastroenterology, Department of Medicine, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Carly E Visentin; Shannon Masih; Lesley Plumptre; Olga Malysheva; Daiva E Nielsen; Kyoung-Jin Sohn; Anna Ly; Andrea Y Lausman; Howard Berger; Ruth Croxford; Ahmed El-Sohemy; Marie A Caudill; Deborah L O'Connor; Young-In Kim Journal: J Nutr Date: 2015-05-13 Impact factor: 4.798
Authors: John T Brosnan; James L Mills; Per M Ueland; Barry Shane; Ruzong Fan; Chi-Yang Chiu; Faith Pangilinan; Lawrence C Brody; Margaret E Brosnan; Theerawat Pongnopparat; Anne M Molloy Journal: Am J Clin Nutr Date: 2018-03-01 Impact factor: 7.045
Authors: Shannon E Washburn; Marie A Caudill; Olga Malysheva; Amanda J MacFarlane; Nathalie A Behan; Brian Harnett; Luke MacMillan; Theerawat Pongnopparat; John T Brosnan; Margaret E Brosnan Journal: Am J Physiol Endocrinol Metab Date: 2015-03-24 Impact factor: 4.310
Authors: Simon G Lamarre; Luke MacMillan; Gregory P Morrow; Edward Randell; Theerawat Pongnopparat; Margaret E Brosnan; John T Brosnan Journal: Amino Acids Date: 2014-04-10 Impact factor: 3.520
Authors: Lesley Plumptre; Shannon P Masih; Anna Ly; Susanne Aufreiter; Kyoung-Jin Sohn; Ruth Croxford; Andrea Y Lausman; Howard Berger; Deborah L O'Connor; Young-In Kim Journal: Am J Clin Nutr Date: 2015-08-12 Impact factor: 7.045
Authors: Yvonne Lamers; Jerry Williamson; Douglas W Theriaque; Jonathan J Shuster; Lesa R Gilbert; Christine Keeling; Peter W Stacpoole; Jesse F Gregory Journal: J Nutr Date: 2009-02-25 Impact factor: 4.798
Authors: Margaret E Brosnan; Garrett Tingley; Luke MacMillan; Brian Harnett; Theerawat Pongnopparat; Jenika D Marshall; John T Brosnan Journal: J Nutr Date: 2020-05-01 Impact factor: 4.798
Authors: Anders K Nilsson; Abdellah Tebani; Daniel Malmodin; Anders Pedersen; Gunnel Hellgren; Chatarina Löfqvist; Ingrid Hansen-Pupp; Mathias Uhlén; Ann Hellström Journal: Front Neurosci Date: 2022-02-17 Impact factor: 4.677