Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation
- PMID:30693532
- DOI: 10.1002/jimd.12009
Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation
Abstract
Vitamin B12 (cobalamin, Cbl) is a nutrient essential to human health. Due to its complex structure and dual cofactor forms, Cbl undergoes a complicated series of absorptive and processing steps before serving as cofactor for the enzymes methylmalonyl-CoA mutase and methionine synthase. Methylmalonyl-CoA mutase is required for the catabolism of certain (branched-chain) amino acids into an anaplerotic substrate in the mitochondrion, and dysfunction of the enzyme itself or in production of its cofactor adenosyl-Cbl result in an inability to successfully undergo protein catabolism with concomitant mitochondrial energy disruption. Methionine synthase catalyzes the methyl-Cbl dependent (re)methylation of homocysteine to methionine within the methionine cycle; a reaction required to produce this essential amino acid and generate S-adenosylmethionine, the most important cellular methyl-donor. Disruption of methionine synthase has wide-ranging implications for all methylation-dependent reactions, including epigenetic modification, but also for the intracellular folate pathway, since methionine synthase uses 5-methyltetrahydrofolate as a one-carbon donor. Folate-bound one-carbon units are also required for deoxythymidine monophosphate and de novo purine synthesis; therefore, the flow of single carbon units to each of these pathways must be regulated based on cellular needs. This review provides an overview on Cbl metabolism with a brief description of absorption and intracellular metabolic pathways. It also provides a description of folate-mediated one-carbon metabolism and its intersection with Cbl at the methionine cycle. Finally, a summary of recent advances in understanding of how both pathways are regulated is presented.
Keywords: folate; hyperhomocysteinemia; methionine cycle; methylmalonic acidemia; one-carbon metabolism; vitamin B12.
© 2018 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
Similar articles
- Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency.Allen RH, Stabler SP, Savage DG, Lindenbaum J.Allen RH, et al.FASEB J. 1993 Nov;7(14):1344-53. doi: 10.1096/fasebj.7.14.7901104.FASEB J. 1993.PMID:7901104Review.
- Biochemistry of B12-cofactors in human metabolism.Kräutler B.Kräutler B.Subcell Biochem. 2012;56:323-46. doi: 10.1007/978-94-007-2199-9_17.Subcell Biochem. 2012.PMID:22116707Review.
- Identification of ABC transporters acting in vitamin B12 metabolism in Caenorhabditis elegans.McDonald MK, Fritz JA, Jia D, Scheuchner D, Snyder FF, Stanislaus A, Curle J, Li L, Stabler SP, Allen RH, Mains PE, Gravel RA.McDonald MK, et al.Mol Genet Metab. 2017 Dec;122(4):160-171. doi: 10.1016/j.ymgme.2017.11.002. Epub 2017 Nov 11.Mol Genet Metab. 2017.PMID:29153845
- Human B12-dependent enzymes: Methionine synthase and Methylmalonyl-CoA mutase.Mascarenhas R, Gouda H, Ruetz M, Banerjee R.Mascarenhas R, et al.Methods Enzymol. 2022;668:309-326. doi: 10.1016/bs.mie.2021.12.012. Epub 2022 Jan 30.Methods Enzymol. 2022.PMID:35589199Free PMC article.
- Recognition of two intracellular cobalamin binding proteins and their identification as methylmalonyl-CoA mutase and methionine synthetase.Kolhouse JF, Allen RH.Kolhouse JF, et al.Proc Natl Acad Sci U S A. 1977 Mar;74(3):921-5. doi: 10.1073/pnas.74.3.921.Proc Natl Acad Sci U S A. 1977.PMID:15259Free PMC article.
Cited by
- Neuroprotective Roles of the Reverse Transsulfuration Pathway in Alzheimer's Disease.Paul BD.Paul BD.Front Aging Neurosci. 2021 Mar 16;13:659402. doi: 10.3389/fnagi.2021.659402. eCollection 2021.Front Aging Neurosci. 2021.PMID:33796019Free PMC article.
- Selection and Mechanism Study of Q-Markers for Xanthocerais lignum Anti-Rheumatoid Arthritis Based on Serum Spectrum-Effect Correlation Analysis.Qian H, Su L, Yang Y, Tian X, Dai Q, Meng F, Wang X.Qian H, et al.Molecules. 2024 Jul 4;29(13):3191. doi: 10.3390/molecules29133191.Molecules. 2024.PMID:38999143Free PMC article.
- Global biogeography and ecological implications of cobamide-producing prokaryotes.Wang J, Zhu YG, Tiedje JM, Ge Y.Wang J, et al.ISME J. 2024 Jan 8;18(1):wrae009. doi: 10.1093/ismejo/wrae009.ISME J. 2024.PMID:38366262Free PMC article.
- Methyl Donors, Epigenetic Alterations, and Brain Health: Understanding the Connection.Bekdash RA.Bekdash RA.Int J Mol Sci. 2023 Jan 25;24(3):2346. doi: 10.3390/ijms24032346.Int J Mol Sci. 2023.PMID:36768667Free PMC article.Review.
- Personalized Nutrition in the Management of Female Infertility: New Insights on Chronic Low-Grade Inflammation.Fabozzi G, Verdone G, Allori M, Cimadomo D, Tatone C, Stuppia L, Franzago M, Ubaldi N, Vaiarelli A, Ubaldi FM, Rienzi L, Gennarelli G.Fabozzi G, et al.Nutrients. 2022 May 3;14(9):1918. doi: 10.3390/nu14091918.Nutrients. 2022.PMID:35565885Free PMC article.Review.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous