Chemistry:Methylcobalamin

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Methylcobalamin (mecobalamin, MeCbl, or MeB12) is a cobalamin, a form of vitamin B12. It differs from cyanocobalamin in that the cyano group at the cobalt is replaced with a methyl group.[1] Methylcobalamin features an octahedral cobalt(III) centre and can be obtained as bright red crystals.[2] From the perspective of coordination chemistry, methylcobalamin is notable as a rare example of a compound that contains metal–alkyl bonds. Nickel–methyl intermediates have been proposed for the final step of methanogenesis.

Production

Methylcobalamin physically resembles the other forms of vitamin B12, occurring as dark red crystals that freely form cherry-colored transparent solutions in water.
a box of generic mecobalamin tablets sold in China

Methylcobalamin can be produced in the laboratory by reducing cyanocobalamin with sodium borohydride in alkaline solution, followed by the addition of methyl iodide.[2]

Functions

This vitamer, along with adenosylcobalamin, is one of two active coenzymes used by vitamin B12-dependent enzymes and is the specific vitamin B12 form used by 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase. Methylcobalamin participates in the Wood-Ljungdahl pathway, which is a pathway by which some organisms utilize carbon dioxide as their source of organic compounds. In this pathway, methylcobalamin provides the methyl group that couples to carbon monoxide (derived from CO2) to afford acetyl-CoA. Acetyl-CoA is a derivative of acetic acid that is converted to more complex molecules as required by the organism.[3]

Methylcobalamin is produced by some bacteria.[citation needed] It plays an important role in the environment, where it is responsible for the biomethylation of certain heavy metals. For example, the highly toxic methylmercury is produced by the action of methylcobalamin.[4] In this role, methylcobalamin serves as a source of "CH3+".

Role in human health

Methylcobalamin is equivalent physiologically to vitamin B12,[5][non-primary source needed] and can be used to prevent or treat pathology arising from a lack of vitamin B12 intake (vitamin B12 deficiency). Methylcobalamin is considered to be equivalent in efficacy to the other vitamin B12 vitamers as a dietary supplement, with no clear evidence of differing efficacy between them.[6][7][8]

Methylcobalamin that is ingested is not used directly as a cofactor, but is first converted by MMACHC into cob(II)alamin. Cob(II)alamin is then later converted into the other two forms, adenosylcobalamin and methylcobalamin for use as cofactors. That is, methylcobalamin is first dealkylated and then regenerated.[9][10][11]

Research directions

Ultra-high-dose intravenous methylcobalamin is researched as treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for amyotrophic lateral sclerosis.[12][13][14][15][16]

See also

References

  1. ↑ Vitamins in animal and human nutrition. Wiley. 2000. ISBN 978-0813826301. https://books.google.com/books?id=dXOPBMYIPcQC&pg=PA526. Retrieved 28 January 2018. 
  2. ↑ 2.0 2.1 "Preparation of the Reduced Forms of Vitamin B12 and of Some Analogs of the Vitamin B12 Coenzyme Containing a Cobalt-Carbon Bond". Vitamins and Coenzymes. Methods in Enzymology. 18. Academic Press. January 1971. pp. 34–54. doi:10.1016/S0076-6879(71)18006-8. ISBN 9780121818821. 
  3. ↑ "Structure-function relationships of anaerobic gas-processing metalloenzymes". Nature 460 (7257): 814–822. August 2009. doi:10.1038/nature08299. PMID 19675641. Bibcode: 2009Natur.460..814F. 
  4. ↑ Comprehensive B12: Chemistry, Biochemistry, Nutrition, Ecology, Medicine, Walter de Gruyter, 1987, ISBN 978-3110082395, https://books.google.com/books?id=OBlxCKbYCx8C&pg=PA32 
  5. ↑ "A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy". The Korean Journal of Pain 31 (3): 183–190. July 2018. doi:10.3344/kjp.2018.31.3.183. PMID 30013732. [non-primary source needed]
  6. ↑ "5′-deoxyadenosylcobalamin and methylcobalamin as sources for Vitamin B12 added as a nutritional substance in food supplements: Scientific opinion of the Scientific Panel on Food Additives and Nutrient Sources added to food". EFSA Journal 815 (10): 1–21. 25 September 2008. doi:10.2903/j.efsa.2008.815. 
  7. ↑ "Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency". Molecular Nutrition & Food Research 59 (7): 1364–1372. 28 March 2015. doi:10.1002/mnfr.201500019. PMID 25820384. 
  8. ↑ "Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus". Journal of Clinical Medicine 13 (8): 2176. 10 April 2024. doi:10.3390/jcm13082176. PMID 38673453. 
  9. ↑ "A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins". The Journal of Biological Chemistry 284 (48): 33418–33424. November 2009. doi:10.1074/jbc.M109.057877. PMID 19801555. 
  10. ↑ "Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product". Molecular Genetics and Metabolism 97 (4): 260–266. August 2009. doi:10.1016/j.ymgme.2009.04.005. PMID 19447654. 
  11. ↑ "Genetic disorders of vitamin B₁₂ metabolism: eight complementation groups–eight genes". Expert Reviews in Molecular Medicine 12: e37. November 2010. doi:10.1017/S1462399410001651. PMID 21114891. 
  12. ↑ "Eisai Submits New Drug Application for Mecobalamin Ultra-High Dose Preparation as Treatment for Amyotrophic Lateral Sclerosis in Japan". http://www.eisai.com/news/enews201535pdf.pdf. 
  13. ↑ "Methylcobalamine is effective in peripheral neuropathies". European Journal of Clinical Nutrition 69 (4): 530. April 2015. doi:10.1038/ejcn.2014.281. PMID 25585598. 
  14. ↑ "Safety and efficacy of methylcobalamin in the treatment of peripheral nerve injuries and diabetic neuropathies-A systematic review.". Acta Scientific Pharmaceutical Sciences 5 (8): 75–80. August 2021. doi:10.31080/ASPS.2021.05.0769. https://actascientific.com/ASPS/pdf/ASPS-05-0769.pdf. Retrieved 8 March 2025. 
  15. ↑ "Meta-analysis of methylcobalamin alone and in combination with prostaglandin E1 in the treatment of diabetic peripheral neuropathy". Endocrine 46 (3): 445–454. August 2014. doi:10.1007/s12020-014-0181-6. PMID 24522613. https://link.springer.com/article/10.1007/s12020-014-0181-6. Retrieved 8 March 2025. 
  16. ↑ "Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study". Journal of Neurology, Neurosurgery, and Psychiatry 90 (4): 451–457. April 2019. doi:10.1136/jnnp-2018-319294. PMID 30636701. 



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