plays a key role in metabolic pathways involved in DNA synthe-sis, epigenetic processes, and proliferation [9, 10]. (1993) reported a twofold higher urinary ApABG excretion by pregnant women during the second trimester relative to nonpregnant controls. The influence of intracellular folate concentration (as governed largely by dietary intake) on the entry and processing of substrate in one-carbon metabolism is uncertain. Folate functions in multiple coenzyme forms in acceptance, redox processing and transfer of one-carbon units, including nucleotides and certain amino acids. Methyl groups are transferred to the N-5 position of cytosine in DNA by a specific DNA methylase. Folate has gained significant attention due to its vital role in biological methylation and epigenetic machinery. Folate and one-carbon metabolism play a central role in cellular physiology because they are intimately involved in the control of purine, pyrimidine, and glutathione synthesis, as well as the methylation of DNA, histones and a host Lynn B. Bailey, Jesse F. Gregory, III, Folate Metabolism and Requirements, The Journal of Nutrition, Volume 129, Issue 4, April 1999, Pages 779–782, https://doi.org/10.1093/jn/129.4.779. Florida Agricultural Experiment Station Journal Series no. Folate is also involved in the supply of methyl groups to the so-called methylation cycle, which uses methionine and makes homocysteine. In addition, the ancillary indicators, serum folate and plasma homocysteine concentrations, also were abnormal in 50% of the group [<3 ng/mL (6.8 nmol/L) and >14 μmol/L, respectively]. Folate assists in the production and maintenance of new cells (such as red blood cells), RNA and DNA. 1997). This is an alternate ISBN. Folate one-carbon metabolism (FOCM) plays an integral role in human development and disease. We have recently reported that the lack of the enzyme due to compound heterozygous mutations was associated with neuro-ichthyotic syndrome in a male patient. 2016, 17, 1208 2 of 26 for essential cellular processes including DNA synthesis and repair and the maintenance of redox status. vitamin metabolism. In poor folate status, S-adenosylhomocysteine (SAH) concentration would tend to increase due to impairment of methyl group synthesis and homocysteine remethylation. Many clinical studies show that when women take folic acid before conception, t… Because one-carbon metabolism is also the major … During periods of inadequate folate intake or malabsorption, biochemical changes associated with inadequate folate status allow the onset of abnormalities in one-carbon metabolism. Feasibility of regenerative adsorption of a hydrofluorocarbon (HFC-134a) using activated carbon fiber studied by the gaseous flow method. Misincorporation of uracil into DNA with chronic folate deficiency is expected to stress the mechanism of DNA repair and thus result in subsequent increases in DNA strand breaks and chromosomal instability (Blount et al. As humans cannot make folate, it is required in the diet, making it an essential nutrient. Adequate folate intake is essential throughout gestation to ensure normal growth and development. Folate is a rate‐limiting and critical vitamin for several different cellular pathways, most notably for DNA synthesis, maintenance, and methylation (McKay et al. (, Cuskelly, G. J., McNulty, H. & Scott, J. M. (, Daly, S., Mills, J. L., Molloy, A. M., Conley, M., Lee, Y. J., Kirke, P. N., Weir, D. G. & Scott, J. M. (, Food and Nutrition Board. These abnormalities (e.g., hyperhomocysteinemia orDNA hypomethylation) may result in deleterious consequences, including increased risk for certain types of chronic diseases (Boushey et al. 1998). For infants, it was not possible to estimate an EAR or RDA due to limitations in the database. ii DEDICATION The principal function of folate coenzymes is to accept or donate one-carbon units in key metabolic pathways (Fig. Folate-requiring reactions, collectively referred to as one-carbon metabolism, include those involved in phases of amino acid metabolism, purine and pyrimidine synthesis, and the formation of the primary methylating agent, S-adenosylmethionine (SAM) (Fig. In contrast, data from our metabolic study in which dietary folate intake was strictly controlled indicated no change in folate catabolism due to pregnancy (Caudill et al. Folate-deficient humans had elevated incorporation of uracil into DNA, accompanied by an increased frequency of cellular micronuclei, a measure of DNA and chromosome damage (Blount et al. The N-5 methyl group of 5-methyl-THF can only be used metabolically for transfer to homocysteine, which results in the (re)generation of methionine. Int. 1993). These findings suggest a pivotal role for B12 in the control of cell growth, which may lead to coordination of cell behavior in complex multicellular systems. OCM cycles and its related micronutrients are ubiquitously present in stem cells and feed into the epigenetic mechanisms. Flux through SHMT would be predicted to be a function of PLP concentrations (Jones and Priest 1978). Homocysteine has two primary metabolic fates as follows: 1) conversion to methionine, and 2) catabolism via the transsulfuration pathway that involves PLP-dependent enzymes cystathionine β-synthase and γ-cystathionase. Folate metabolism performs major housekeeping functions in the cell by synthesizing substrates necessary for DNA synthesis and repair as well as methylation of DNA, protein and RNA. The biochemical functions and regulation of individual proteins within these pathways are discussed, along with the biochemical/cellular consequences of their dysfunction. Probable benefits of increasing folic acid intakes, Folate status response to controlled folate intake in pregnant women, Folate catabolism in pregnant and nonpregnant women with controlled folate intakes, Effect of increasing dietary folate on red cell folate: implications for prevention of neural tube defects, Minimum effective dose of folic acid for food fortification to prevent neural tube defects, Food and Nutrition Board. of experiments in rodents, Iskandar and colleagues demonstrate a crucial role of folate in the regeneration of afferent spinal neurons after injury. 1997). The EAR for folate is defined as the amount of folate that is needed to meet the requirement of 50% of the population. synth... Get solutions In particular, the circulation of folate and methionine in 1-carbon metabolism generates S-adenosyl methionine (SAM), a major methyl group donor, which is required for numerous biological reactions  . Research output: Contribution to journal › Article › peer-review. An example of the type of study on which the EAR for adults is based is that of O'Keefe et al. Mitochondrial folate enzyme ALDH1L2 (aldehyde dehydrogenase 1 family member L2) converts 10-formyltetrahydrofolate to tetrahydrofolate and CO2 simultaneously producing NADPH. This provides new insight into potential resistance mechanisms and This provides new insight into potential resistance mechanisms and chemotherapy strategies using antifolates. The Recommended Dietary Allowances (RDA) were estimated from the EAR by correcting for population variance and were defined as the average level of daily dietary intake sufficient to meet the nutrient requirement of ∼98% of the population. Although other sources of one-carbon units exist (e.g., choline, formate, glycine or betaine), serine appears to be the primary carbon donor for the diverse processes of one-carbon metabolism (Pasternack et al. Characterization of the folate-dependent mitochondrial oxidation of carbon 3 of serine, Plasma homocysteine as a risk factor for vascular disease, Clinical implications of hyperhomocysteinemia, Kinetic model of folate metabolism in nonpregnant women consuming [, Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women, Interaction of pyridoxal 5-phosphate with apo-serine hydroxymethyltransferase, Role of mitochondrial and cytoplasmic serine hydroxymethyltransferase isozymes de novo purine synthesis in, Clinical spectrum and diagnosis of folate deficiency, Accelerated folate breakdown in pregnancy, Folate-deficiency-induced homocysteinaemia in rats:disruption of, Controlled dietary folate affects folate status in nonpregnant women, Dietary and serum folate: their influence on the outcome of pregnancy, Absorption of folate from fortified cereal-grain products and of supplemental folates consumed with or without food determined using a dual-label stable-isotope protocol, Folate and vitamin B-6 from diet and supplements in relation to risk of coronary heart disease among women, Folate requirement and metabolism in nonpregnant women, Vitamin status and primary determinants of homocysteinemia in an elderly population, The pathogenesis of homocysteinemia: interruption of the coordinate regulation of, Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis, Serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyl-tetrahydrofolate, 5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase, Biochemical role of folate in cellular metabolism, Folate deficiency in the alcoholic: its relationship to clinical and haematological abnormalities, liver disease, and folate stores, © 1999 The American Society for Nutritional Sciences, Replacing Animal Protein with Soy-Pea Protein in an “American Diet” Controls Murine Crohn Disease–Like Ileitis Regardless of Firmicutes: Bacteroidetes Ratio, Cardiometabolic Risk is Positively Associated with Underreporting and Inversely Associated with Overreporting of Energy Intake Among European Adolescents: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study, High Serum Folate Concentrations Are Associated with Decreased Risk of Mortality among Japanese Adults, Supplemental Berberine in a High-Fat Diet Reduces Adiposity and Cardiac Dysfunction in Offspring of Mouse Dams with Gestational Diabetes Mellitus, Sex Differences in the Plasma Accumulation of Oxylipins in Response to Supplemental n–3 Fatty Acids, Food Environment and Supply on Dietary and Lifestyle Choices. 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