Skip to main content
SpringerLink
Log in
Book cover

Folates and Cobalamins pp 41–51Cite as

Cobalamin-Folate Interrelations

  • Chapter

Abstract

While the biochemical roles of cobalamin and folate have been well defined for many years, the complex manner in which they interrelate in vivo and the mechanism by which cobalamin deficiency produces megaloblastosis in man remains unclear. Cobalamin is a coenzyme in two well-studied reactions in mammals: the synthesis of methionine by methylation of homocysteine and the conversion of methylmalonyl-CoA to succinyl-CoA by an intra-molecular rearrangement. Folate is a coenzyme in a variety of reactions by which single C units (C-l) are transferred from carbon donors such as serine, formate, methionine and histidine and are donated in the synthesis of purines, pyrimidines and methionine.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Waters AH, Mollin DL (1961) Studies on the folic acid activity of human serum. J Clin Pathol 14:335–344

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Herbert V (1961) The assay and nature of folic acid activity in human serum. J Clin Invest 40:81–91

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Chanarin I (1979) The megaloblastic anaemias, 2nd edn. Blackwell, Oxford, pp 138–140

    Google Scholar 

  4. Das KC, Hoffbrand AV (1970) Studies of folate uptake by phytohaemagglutinin-stimulated lymphocytes. Br J Haematol 19:203–221

    Article  PubMed  CAS  Google Scholar 

  5. Tisman G, Herbert V (1973) B12-dependence of cell uptake of serum folate: an explanation for the high serum folate and cell folate depletion in B12 deficiency. Blood 41:465–469

    PubMed  CAS  Google Scholar 

  6. Lumb M, Perry J, Deacon R, Chanarin I (1981) Change in plasma folate levels in rats inhaling nitrous oxide. Scand J Haematol 26:61–64

    Article  PubMed  CAS  Google Scholar 

  7. Perry J, Chanarin I, Deacon R, Lumb M (1983) Chronic cobalamin inactivation impairs folate polyglutamate synthesis in the rat. J Clin Invest 71:1183–1190

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Chanarin I (1979) The megaloblastic anaemias, 2nd edn. Blackwell, Oxford pp297–298

    Google Scholar 

  9. Chanarin I (1979) The megaloblastic anaemias, 2nd edn Blackwell, Oxford pp293–295

    Google Scholar 

  10. Van der Westhuyzen J, Fernandes-Costa F, Metz J (1982) Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates. Life Sci 31:2001–2010

    Article  PubMed  Google Scholar 

  11. Herbert V, Zalusky R (1962) Interrelationship of vitamin B12 and folic acid metabolism: folic acid clearance studies. J Clin Invest 41:1263–1267

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Noronha JM, Silverman M (1962) On folic acid, vitamin B12, methionine and formiminoglutamic acid. In: Heinrich HC (ed) Vitamin B12 und intrinsic factor 2. Enke, Stuttgart, pp728–736

    Google Scholar 

  13. Kutzbach C, Stokstad ELR (1971) Mammalian methylenetetrahydrofolate reductase, partial purification, properties and inhibition by S-adenosylmethionine. Biochim Biophys Acta 250:459–477

    Article  PubMed  CAS  Google Scholar 

  14. Deacon R, Chanarin I, Perry J, Lumb M (1981) The effect of folate analogues on thymidine utilization by human and rat marrow cells and the effect on the deoxyuridine suppression test. Postgrad Med J 57:611–616

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Deacon R, Chanarin I, Perry J, Lumb M (1982) A comparison of tetrahydrofolate and 5-formyltetrahydrofolate in correcting the impairment of thymidine synthesis in pernicious anaemia. Br J Haematol 28:289–292

    CAS  Google Scholar 

  16. Taheri MR, Wickremasinghe RG, Jackson BFA, Hoffbrand AV (1982) The effect of folate analogues and vitamin B12 on provision of thymidine nucleotides for DNA synthesis in megaloblastic anaemia. Blood 59:634–640

    PubMed  CAS  Google Scholar 

  17. Deacon R, Chanarin I, Perry J, Lumb M (1980) Impaired deoxyuridine utilization in the B]2-inactivated rat and its correction by folate analogues. Biochem Biophys Res Commun 93:516–520

    Article  PubMed  CAS  Google Scholar 

  18. Banks RGS, Henderson RJ, Pratt JM (1968) Reactions of gases in solution. Part III. Some reactions of nitrous oxide with transition-metal complexes. J Chem Soc (A) 2886–2889

    Article  Google Scholar 

  19. Lassen HCA, Henriksen E, Neukirch F, Kristensen AS (1956) Treatment of tetanus. Severe bone marrow depression after prolonged nitrous-oxide anaesthesia. Lancet 1:527–530

    Article  Google Scholar 

  20. Amess JAL, Burman JF, Rees GM, Nancekievill DG, Mollin DL (1978) Megaloblastic haemopoiesis in patients receiving nitrous oxide. Lancet ii: 339–342

    Article  Google Scholar 

  21. Layzer RB (1978) Myeloneuropathy after prolonged expsure to nitrous oxide. Lancet ii: 1227–1230

    Article  Google Scholar 

  22. Deacon R, Lumb M, Perry J, Chanarin I, Minty B, Halsey MJ, Nunn JF (1978) Selective inactivation of vitamin B12 in rats by nitrous oxide. Lancet ii: 1023–1024

    Google Scholar 

  23. Lumb M, Chanarin I, Perry J, Deacon R (1985) Turnover of the methyl moiety of 5-methyl-tetrahydropteroylglutamic acid in the cobalamin-inactivated rat. Blood 66 (5): 1171–1175

    PubMed  CAS  Google Scholar 

  24. Brody T, Watson JE, Stokstad ELR (1982) Folate pentaglutamate and folate hexaglutamate mediated one-carbon metabolism. Biochemistry 21:276–282

    Article  PubMed  CAS  Google Scholar 

  25. Laduron P (1972) N-methylation od dopamine to epinine in brain tissue using TV-methylte-trahydrofolic acid as the methyl donor. Nature 238:212–213

    Article  CAS  Google Scholar 

  26. Leysen J, Laduron P (1974) Characterization of an enzyme yielding formaldehyde from 5-methyltetrahydrofolic acid. FEBS Lett 47:299–303

    Article  PubMed  CAS  Google Scholar 

  27. Taylor RT, Hanna ML (1975) 5-Methyltetrahydrofolate aromatic alkylamine N-methyl-transferase: an artefact of 5,10-methylenetetrahydrofolate reductase activity. Life Sci 17:111–120

    Article  PubMed  CAS  Google Scholar 

  28. Pearson AGM, Turner AJ (1975) Folate-dependent 1-carbon transfer to biogenic amines mediated by methylenetetrahydrofolate reductase. Nature 258:173–174

    Article  PubMed  CAS  Google Scholar 

  29. Thorndike J, Beck WS (1977) Production of formaldehyde from N5-methyltetrahydrofolate by normal and leukemic leukocytes. Cancer Res 37:1125–1132

    PubMed  CAS  Google Scholar 

  30. Kondo H, Osborne ML, Kolhouse JF, Binder MJ, Podell ER, Utley CS, Abrams RS, Allen RH (1981) Nitrous oxide has multiple deleterious effects on cobalamin metabolism and cause decreases in activities of both mammalian cobalamin-dependent enzymes in rats. J Clin Invest 67:1270–1283

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Lumb M, Perry J, Deacon R, Chanarin I (1982) Urinary folate loss following inactivation of vitamin B12 by nitrous oxide in rats. Br J Haematol 51:235–242

    Article  PubMed  CAS  Google Scholar 

  32. Lumb M, Deacon R, Perry J, Chanarin I, Minty B, Halsey MJ, Nunn JF (1980) The effect of nitrous oxide inactivation of vitamin B12 on rat hepatic folate. Implications for the methylfolate trap hypothesis. Biochem J 186:933–966

    PubMed  CAS  PubMed Central  Google Scholar 

  33. Lumb M, Perry J, Deacon R, Chanarin I (1981) Recovery of tissue folate after inactivation of cobalamin by nitrous oxide. The significance of dietary folate. Am J Clin Nutr 34:2418–2422

    PubMed  CAS  Google Scholar 

  34. Perry J, Chanarin I, Deacon R, Lumb M (1979) The substrate for folate polyglutamate biosynthesis in the vitamin B12-inactivated rat. Biochem Biophys Res Commun 91:678–684

    Article  PubMed  CAS  Google Scholar 

  35. Perry J, Chanarin I, Deacon R, Lumb M (1985) Folate polyglutamate synthetase activity in the cobalamin-inactivated rat. Biochem J 227:73–77

    PubMed  CAS  PubMed Central  Google Scholar 

  36. Trackman PC, Abeles RH (1981) The metabolism of l-phospho-5-methyl-thioribose. Biochem Biophys Res Commun 103:1238–1244

    Article  PubMed  CAS  Google Scholar 

  37. Lumb M, Sharer N, Deacon R, Jennings P, Purkiss P, Perry J, Chanarin I (1983) Effects of nitrous oxide-induced inactivation of cobalamin on methionine and S-adenosylmethionine metabolism in the rat. Biochim Biophys Acta 756:354–359

    Article  PubMed  CAS  Google Scholar 

  38. Sakamoto S, Niina M, Takaku F (1975) Thymidylate synthetase activity in bone marrow cells in pernicious anemia. Blood 46:699–704

    PubMed  CAS  Google Scholar 

  39. Deacon R, Perry J, Lumb M, Chanarin I (1981) The effect of nitrous oxide-induced inactivation of vitamin B12 on thymidylate synthetase activity of rat bone marrow cells. Biochem Biophys Acta 102:215–218

    CAS  Google Scholar 

  40. Deacon R, Perry J, Lumb M, Chanarin I (1980) The effect of nitrous oxide-induced inactivation of vitamin B12 on serine transhydroxymethylase. Biochem Biophys Res Common 97:1324–1328

    Article  CAS  Google Scholar 

  41. Sourial NA, Brown I (1983) Regulation of cobalamin and folate metabolism by methionine in human bone marrow cultures. Scand J Haematol 31:413–423

    Article  PubMed  CAS  Google Scholar 

  42. Cheng FW, Shane B, Stakstad ELR (1975) The antifolate effect of methionine on bone marrow of normal and vitamin B12 deficient rats. Br J Haematol 31:323–336

    Article  PubMed  CAS  Google Scholar 

  43. Perry J, Deacon R, Lumb M, Chanarin I (1980) The effect of nitrous-oxide induced inactivation of vitamin B12 on the activity of formyl-methenyl-methylenetetrahydrofolate synthetase, methylenetetrahydrofolate reductase and formiminotetrahydrofolate transferase. Biochem Biophys Res Commun 97:1329–1333

    Article  PubMed  CAS  Google Scholar 

  44. Deacon R, Perry J, Lumb M, Chanarin I (1983) Effect of nitrous oxide-induced inactivation of vitamin B12 on glycinamide ribonucleotide transformylase and 5-amino-4-imidazole carboxamide transformylase. Biochem Biophys Res Commun 112:327–331

    Article  PubMed  CAS  Google Scholar 

  45. Gawthorne JM, Smith RM (1974) Folic acid metabolism in vitamin B12-deficient sheep. Effects of injected methionine on methotrexate transport and the activity of enzymes associated with folate metabolism in liver. Biochem J 142:119–126

    PubMed  CAS  PubMed Central  Google Scholar 

  46. Chanarin I, Deacon R, Lumb M, Perry J (1980) Vitamin B12 regulates folate metabolism by the supply of formate. Lancet ii: 505–508

    Article  Google Scholar 

  47. Chanarin I, Deacon R, Lumb M, Muir M, Perry J (1985) Cobalamin-folate interrelations – a critical review. Blood 66 (3): 479–489

    PubMed  CAS  Google Scholar 

  48. Scott JM, Dinn JJ, Wilson P, Weir DG (1981) Pathogenesis of subacute combined degeneration: a result of methyl group deficiency. Lancet ii:334–337

    Article  Google Scholar 

  49. Miller H, Fernandes-Costa F, Metz J (1980) Synthesis of DNA as shown by the deoxyuridine suppression test is normal in the vitamin B12-deficient fruit bat (Rosettus aegyptiacus). Br J Nutr 44:229–435

    Article  PubMed  CAS  Google Scholar 

  50. Benevenga J, Radcliffe BC, Egan AR (1983) Tissue metabolism of methionine in sheep. Aust J Biol Sci 36:475–485

    PubMed  CAS  Google Scholar 

  51. Lumb M, Chanarin I, Deacon R, Perry J (1988) In vitro oxidation of the methyl group of hepatic 5-methyltetrahydrofolate. J Clin Path 41:1158–1162

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Authors
  1. I. Chanarin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division d’Hématologie et d’Oncologie médicale, Hôpital Royal Victoria et Département de Médecine interne et de Physiologie, Université McGill, Montréal, Québec, Canada

    Bernard A. Cooper

  2. Laboratoire d’Hématologie, Hôpital Henri Mondor et Faculté de Médecine, 94010, Créteil, France

    Jacqueline A. Zittoun

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Chanarin, I. (1989). Cobalamin-Folate Interrelations. In: Cooper, B.A., Zittoun, J.A. (eds) Folates and Cobalamins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74364-1_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74364-1_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-50653-9

  • Online ISBN: 978-3-642-74364-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation