Methylcobalamin

File:B12 methylcobalamin.jpg

File:Mecobalamin tablets.jpg 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.{{cite book | vauthors = David D |title=Vitamins and Coenzymes | chapter = Preparation of the Reduced Forms of Vitamin B₁₂ and of Some Analogs of the Vitamin B₁₂ Coenzyme Containing a Cobalt-Carbon Bond| veditors = McCormick DB, Wright LD | series = Methods in Enzymology | volume = 18 | pages = 34–54| date = January 1971| doi = 10.1016/S0076-6879(71)18006-8 | publisher = Academic Press |isbn=9780121818821 }}

This vitamer, along with adenosylcobalamin, is one of two active coenzymes used by vitamin B{{sub|12}}-dependent enzymes and is the specific vitamin B{{sub|12}} form used by 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase.{{citation needed|date=January 2014}}

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.{{cite journal | vauthors = Fontecilla-Camps JC, Amara P, Cavazza C, Nicolet Y, Volbeda A | title = Structure-function relationships of anaerobic gas-processing metalloenzymes | journal = Nature | volume = 460 | issue = 7257 | pages = 814–822 | date = August 2009 | pmid = 19675641 | doi = 10.1038/nature08299 | bibcode = 2009Natur.460..814F | s2cid = 4421420 }}

Methylcobalamin is produced by some bacteria.{{cn|date=February 2021}} 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.{{citation |url=https://books.google.com/books?id=OBlxCKbYCx8C&pg=PA32 |title=Comprehensive B12: Chemistry, Biochemistry, Nutrition, Ecology, Medicine | vauthors = Schneider Z, Stroiński A |isbn=978-3110082395 |year=1987 |publisher=Walter de Gruyter }} In this role, methylcobalamin serves as a source of "CH₃⁺".

Methylcobalamin is equivalent physiologically to vitamin B{{sub|12}},{{cite journal | vauthors = Sil A, Kumar H, Mondal RD, Anand SS, Ghosal A, Datta A, Sawant SV, Kapatkar V, Kadhe G, Rao S | title = 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 | journal = The Korean Journal of Pain | volume = 31 | issue = 3 | pages = 183–190 | date = July 2018 | pmid = 30013732 | pmc = 6037815 | doi = 10.3344/kjp.2018.31.3.183 }}{{non-primary source needed|date=December 2024}}{{non-primary source needed|date=December 2024}} and can be used to prevent or treat pathology arising from a lack of vitamin B{{sub|12}} 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.{{cite journal | vauthors = Aguilar F, Charrondiere U, Dusemund B, Galtier P, Gilbert J, Gott DM, Grilli S, Guertler R, Kass GE, Koenig J, Lambré C, Larsen JC, Leblanc JC, Mortensen A, Parent-Massin D, Pratt I, Rietjens I, Stankovic I, Tobback P, Verguieva T, Woutersen R | collaboration = European Food Safety Authority | date = 25 September 2008 | title = 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 | journal = EFSA Journal | volume = 815 | issue = 10| pages = 1–21 | doi = 10.2903/j.efsa.2008.815 | doi-access = free }}{{cite journal|date=28 March 2015|doi=10.1002/mnfr.201500019 |title=Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency |journal=Molecular Nutrition & Food Research |volume=59 |issue=7 |pages=1364–1372 |pmid=25820384 |pmc=4692085 | vauthors = Obeid R, Fedosov SN, Nexo E }}{{cite journal|doi=10.3390/jcm13082176|date=10 April 2024|doi-access=free |title=Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus |journal=Journal of Clinical Medicine |volume=13 |issue=8 |page=2176 |pmid=38673453 | vauthors = Obeid R, Andrès E, Češka R, Hooshmand B, Guéant-Rodriguez R, Prada GI, Sławek J, Traykov L, Ta Van B, Várkonyi T, Reiners K |pmc=11050313 }}

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.{{cite journal | vauthors = Kim J, Hannibal L, Gherasim C, Jacobsen DW, Banerjee R | title = A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins | journal = The Journal of Biological Chemistry | volume = 284 | issue = 48 | pages = 33418–33424 | date = November 2009 | pmid = 19801555 | pmc = 2785186 | doi = 10.1074/jbc.M109.057877 | doi-access = free }}{{cite journal | vauthors = Hannibal L, Kim J, Brasch NE, Wang S, Rosenblatt DS, Banerjee R, Jacobsen DW | title = Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product | journal = Molecular Genetics and Metabolism | volume = 97 | issue = 4 | pages = 260–266 | date = August 2009 | pmid = 19447654 | pmc = 2709701 | doi = 10.1016/j.ymgme.2009.04.005 }}{{cite journal | vauthors = Froese DS, Gravel RA | title = Genetic disorders of vitamin B₁₂ metabolism: eight complementation groups–eight genes | journal = Expert Reviews in Molecular Medicine | volume = 12 | pages = e37 | date = November 2010 | pmid = 21114891 | pmc = 2995210 | doi = 10.1017/S1462399410001651 }}

Ultra-high-dose intravenous methylcobalamin is researched as treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for amyotrophic lateral sclerosis.{{cite web |url= http://www.eisai.com/news/enews201535pdf.pdf |title= Eisai Submits New Drug Application for Mecobalamin Ultra-High Dose Preparation as Treatment for Amyotrophic Lateral Sclerosis in Japan |website= Eisai.com |access-date= 28 January 2018 |archive-date= 17 April 2016 |archive-url= https://web.archive.org/web/20160417160649/http://www.eisai.com/news/enews201535pdf.pdf |url-status= live }}{{cite journal | vauthors = Naik SU, Sonawane DV | title = Methylcobalamine is effective in peripheral neuropathies | journal = European Journal of Clinical Nutrition | volume = 69 | issue = 4 | pages = 530 | date = April 2015 | pmid = 25585598 | doi = 10.1038/ejcn.2014.281 }}{{cite journal | vauthors = Vyloppilli S, Thangavelu A, Vichattu SV, Sayd S | title = Safety and efficacy of methylcobalamin in the treatment of peripheral nerve injuries and diabetic neuropathies-A systematic review. | journal = Acta Scientific Pharmaceutical Sciences | date = August 2021 | volume = 5 | issue = 8 | pages = 75–80 | doi = 10.31080/ASPS.2021.05.0769 | url = https://actascientific.com/ASPS/pdf/ASPS-05-0769.pdf |access-date=8 March 2025 |archive-date=27 September 2023 |archive-url = https://web.archive.org/web/20230927145608/https://www.actascientific.com/ASPS/pdf/ASPS-05-0769.pdf |url-status=live }}{{cite journal | vauthors = Deng H, Yin J, Zhang J, Xu Q, Liu X, Liu L, Wu Z, Ji A | title = Meta-analysis of methylcobalamin alone and in combination with prostaglandin E1 in the treatment of diabetic peripheral neuropathy | journal = Endocrine | volume = 46 | issue = 3 | pages = 445–454 | date = August 2014 | pmid = 24522613 | doi = 10.1007/s12020-014-0181-6 | url = https://link.springer.com/article/10.1007/s12020-014-0181-6 | access-date = 8 March 2025 | url-status = live | archive-url = https://web.archive.org/web/20230428111335/https://link.springer.com/article/10.1007/s12020-014-0181-6 | archive-date = 28 April 2023 | url-access = subscription }}{{cite journal | vauthors = Kaji R, Imai T, Iwasaki Y, Okamoto K, Nakagawa M, Ohashi Y, Takase T, Hanada T, Shimizu H, Tashiro K, Kuzuhara S | title = Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 90 | issue = 4 | pages = 451–457 | date = April 2019 | pmid = 30636701 | pmc = 6581107 | doi = 10.1136/jnnp-2018-319294 | url = }}

• Adenosylcobalamin
• Cyanocobalamin
• Hydroxocobalamin
• Vitamin B12
• Cobalamin biosynthesis

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{{Vitamin}}

{{Enzyme cofactors}}

Category:B vitamins

Category:Cofactors

Category:Methylating agents

Category:Organocobalt compounds

Category:Vitamin B12