Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Folic acid Action Pathway (New)
Homo sapiens
Drug Action Pathway
Folic acid is a nutrient used to treat megaloblastic anemia and is found in many supplements. Folic acid, also known as folate or Vitamin B9, is a member of the B vitamin family and an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. For example, folic acid is present in green vegetables, beans, avocado, and some fruits. Inadequate folate levels can result in a number of health concerns including cardiovascular disease, megaloblastic anemias, cognitive deficiencies, and neural tube defects (NTDs). Folic acid is typically supplemented during pregnancy to prevent the development of NTDs and in individuals with alcoholism to prevent the development of neurological disorders, for example. In order to function within the body, folic acid must first be reduced in the liver by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). THF is converted to 5,10-Methylene-THF. 5,10-Methylene-THF is involved in the metabolism of the purine uracil. Uracil is converted to deoxyuridine by the enzyme Uridine phosphorylase 2, then to deoxyuridine monophosphate using the enzyme thymidine synthase. Thymidylate synthase requires 5,10-Methylene-THF to be converted deoxyuridine monophosphate to deoxythymidine monophosphate. This same enzyme converts deoxythymidine monophosphate to deoxythymidine diphosphate. Finally, deoxythymidine diphosphate forms deoxythymdine triphosphate via the enzyme adenylate kinase 9. Deoxythymdine triphosphate is required for DNA synthesis. 5,10-Methylene-THF can also be converted to 5-Methyltetrahydrofolic acid in the liver. 5-Methyltetrahydrofolic acid converts homocysteine to methionine in erythroblasts. Tetrahydrofolic acid can also form 10-Formyltetrahydrofolate which is used in purine metabolism. This reaction cascade eventually leads to the formation of GTP and ATP which are used in RNA synthesis. The nculeosides dGTP and dATP are also formed, and these are essential for DNA synthesis. Methionine is needed to form s-adenosylmethionine through the enzyme methionine adenosyltransferase. S-Adenosylmethionine is used in DNA methylation. DNA methylation is necessary to regulate gene expression, among other things. In erythropoiesis, erythroblasts are undergoing proliferation and differentiation to form erythrocytes, lots of DNA replication. Deficiency of folate inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes erythroblast apoptosis, resulting in anemia from ineffective erythropoiesis (megaloblastic anemia). Therefore, folate is needed for erythroblasts to survive proliferation and differentiation to form healthy erythrocytes.
References
Folic acid Pathway (New) References
Zhao, R., Diop-Bove, N., Visentin, M., & Goldman, I. D. (2011). Mechanisms of membrane transport of folates into cells and across epithelia. Annual review of nutrition, 31, 177–201. https://doi.org/10.1146/annurev-nutr-072610-145133
Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M: KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551. doi: 10.1093/nar/gkaa970.
Pubmed: 33125081
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037.
Higdon, J. (2022, January 3). Folate. Oregon State University. Retrieved March 16, 2022, from https://lpi.oregonstate.edu/mic/vitamins/folate
Abbasi, I. H., Abbasi, F., Wang, L., Abd El Hack, M. E., Swelum, A. A., Hao, R., Yao, J., & Cao, Y. (2018). Folate promotes S-adenosyl methionine reactions and the microbial methylation cycle and boosts ruminants production and reproduction. AMB Express, 8(1). https://doi.org/10.1186/s13568-018-0592-5
Merrell BJ, McMurry JP: Folic Acid
Pubmed: 32119374
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Settings