The Concept of Folic Acid in Health and Disease - PubMed (original) (raw)
Review
The Concept of Folic Acid in Health and Disease
Yulia Shulpekova et al. Molecules. 2021.
Abstract
Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential one-carbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.
Keywords: antifolates; folate overload; folate transporters; folic acid.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Figure 1
Chemical structure of (a) folic acid and its metabolically active derivates: (b) dihydrofolate, (c) tetrahydrofolic acid, (d) 5-methyltetrahydrofolate.
Figure 2
Schematic location and functioning of cellular folate transporters: (a) reduced folate carrier (RFC), (b) folate receptors (FR), (c) proton-coupled folate transporter (PCFT), (d) efflux pumps—multidrug resistance proteins (MRP), organic anion transporters (OAT), breast cancer resistance protein (BCRP). An apical surface of polarized epithelial cells is marked by irregular contour. In non-FRα-mediated transport, 5-methyl-THF rapidly converts into polyglutamates while in FRα-mediated transport it is rather moved transcellularly.
Figure 2
Schematic location and functioning of cellular folate transporters: (a) reduced folate carrier (RFC), (b) folate receptors (FR), (c) proton-coupled folate transporter (PCFT), (d) efflux pumps—multidrug resistance proteins (MRP), organic anion transporters (OAT), breast cancer resistance protein (BCRP). An apical surface of polarized epithelial cells is marked by irregular contour. In non-FRα-mediated transport, 5-methyl-THF rapidly converts into polyglutamates while in FRα-mediated transport it is rather moved transcellularly.
Figure 3
Cellular cycles involving folates. The names of enzymes are marked by red. Intracellular transformations of 5-methyl-THF may depend on the way of absorption. The steps where NAD+/NADH is involved are marked by blue circles. Adapted from [139].
Similar articles
- New perspectives on folate transport in relation to alcoholism-induced folate malabsorption--association with epigenome stability and cancer development.
Hamid A, Wani NA, Kaur J. Hamid A, et al. FEBS J. 2009 Apr;276(8):2175-91. doi: 10.1111/j.1742-4658.2009.06959.x. Epub 2009 Mar 9. FEBS J. 2009. PMID: 19292860 Review. - The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis.
Assaraf YG. Assaraf YG. Drug Resist Updat. 2006 Aug-Oct;9(4-5):227-46. doi: 10.1016/j.drup.2006.09.001. Epub 2006 Nov 7. Drug Resist Updat. 2006. PMID: 17092765 Review. - Folylpoly-γ-glutamate synthetase: A key determinant of folate homeostasis and antifolate resistance in cancer.
Raz S, Stark M, Assaraf YG. Raz S, et al. Drug Resist Updat. 2016 Sep;28:43-64. doi: 10.1016/j.drup.2016.06.004. Epub 2016 Jul 4. Drug Resist Updat. 2016. PMID: 27620954 Review. - Mechanisms of membrane transport of folates into cells and across epithelia.
Zhao R, Diop-Bove N, Visentin M, Goldman ID. Zhao R, et al. Annu Rev Nutr. 2011 Aug 21;31:177-201. doi: 10.1146/annurev-nutr-072610-145133. Annu Rev Nutr. 2011. PMID: 21568705 Free PMC article. Review. - Folic acid with or without vitamin B12 for cognition and dementia.
Malouf M, Grimley EJ, Areosa SA. Malouf M, et al. Cochrane Database Syst Rev. 2003;(4):CD004514. doi: 10.1002/14651858.CD004514. Cochrane Database Syst Rev. 2003. PMID: 14584018 Updated. Review.
Cited by
- Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.
Sobral AF, Cunha A, Silva V, Gil-Martins E, Silva R, Barbosa DJ. Sobral AF, et al. Int J Mol Sci. 2024 Aug 28;25(17):9339. doi: 10.3390/ijms25179339. Int J Mol Sci. 2024. PMID: 39273288 Free PMC article. Review. - Folic Acid as a Potential Vitamin in Glycemic Control: A Systematic Review.
Aydoğdu GS, Akyakar B, Kalaycı Z, Uçar A, Gezmen-Karadağ M. Aydoğdu GS, et al. Curr Nutr Rep. 2024 Sep 10. doi: 10.1007/s13668-024-00565-5. Online ahead of print. Curr Nutr Rep. 2024. PMID: 39251542 Review. - Mass spectrometry of water-soluble vitamins to establish a risk model for predicting recurrent spontaneous abortion.
Wu B, Li Z, Peng B, Yang Q, Jiang W, Ma Y, Tang J, Yang Y. Wu B, et al. Sci Rep. 2024 Sep 6;14(1):20830. doi: 10.1038/s41598-024-71986-z. Sci Rep. 2024. PMID: 39242673 Free PMC article. - Controlled Cultivation Confers Rhodiola rosea Synergistic Activity on Muscle Cell Homeostasis, Metabolism and Antioxidant Defense in Primary Human Myoblasts.
Iannuzzo F, Schiano E, Pastore A, Guerra F, Tenore GC, Novellino E, Stornaiuolo M. Iannuzzo F, et al. Antioxidants (Basel). 2024 Aug 18;13(8):1000. doi: 10.3390/antiox13081000. Antioxidants (Basel). 2024. PMID: 39199244 Free PMC article. - Facile synthesis of N-doped graphene quantum dots as a fluorescent sensor for Cr(vi) and folic acid detection.
Ni CS, Zhang WJ, Bi WZ, Wu MX, Feng SX, Chen XL, Qu LB. Ni CS, et al. RSC Adv. 2024 Aug 22;14(36):26667-26673. doi: 10.1039/d4ra05016a. eCollection 2024 Aug 16. RSC Adv. 2024. PMID: 39175673 Free PMC article.
References
- Feirer N., Fuqua C. Pterin function in bacteria. Pteridines. 2017;28 doi: 10.1515/pterid-2016-0012. - DOI
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical