Methylcobalamin

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.

Methylcobalamin

Clinical data
Trade names	Cobolmin
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth, sublingual, injection.
ATC code	B03BA05 (WHO)
Legal status
Legal status	US: OTC
Identifiers
IUPAC name carbanide; cobalt(3+);
CAS Number	13422-55-4 Y
PubChem CID	6436232
ChemSpider	29368587
UNII	BR1SN1JS2W
ChEMBL	ChEMBL1697757 N
CompTox Dashboard (EPA)	DTXSID5048631
ECHA InfoCard	100.033.200
Chemical and physical data
Formula	C63H91CoN13O14P
Molar mass	1344.405 g·mol−1
3D model (JSmol)	Interactive image
SMILES [CH3-].CC1=CC2=C(C=C1C)N(C=N2)C3C(C(C(O3)CO)OP(=O)([O-])OC(C)CNC(=O)CCC4(C(C5C6(C(C(C(=N6)C(=C7C(C(C(=N7)C=C8C(C(C(=N8)C(=C4[N-]5)C)CCC(=O)N)(C)C)CCC(=O)N)(C)CC(=O)N)C)CCC(=O)N)(C)CC(=O)N)C)CC(=O)N)C)O.[Co+3]
InChI InChI=1S/C62H90N13O14P.CH3.Co/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);1H3;/q;-1;+3/p-2 Key:ZFLASALABLFSNM-UHFFFAOYSA-L
NY (what is this?)  (verify)

Methylcobalamin is equivalent physiologically to vitamin B₁₂,^[3] and can be used to prevent or treat pathology arising from a lack of vitamin B₁₂ intake (vitamin B₁₂ deficiency).

Methylcobalamin is also used in the treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for amyotrophic lateral sclerosis.^[4]

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.^[5][6][7]

According to one author, it is important to treat vitamin B₁₂ deficiency with hydroxocobalamin or cyanocobalamin or a combination of adenosylcobalamin and methylcobalamin, and not methylcobalamin alone.^[8]

Production

Methylcobalamin physically resembles the other forms of vitamin B₁₂, occurring as dark red crystals that freely form cherry-colored transparent solutions in water.

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.^{[citation needed]}

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.^[9]

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.^[10] In this role, methylcobalamin serves as a source of "CH₃⁺".

A lack of cobalamin can lead to megaloblastic anemia and subacute combined degeneration of the spinal cord.^[11]

See also

• Cobamamide
• Cyanocobalamin
• Hydroxocobalamin
• Vitamin B12
• Cobalamin biosynthesis

References

1. McDowell LR (2000). Vitamins in animal and human nutrition. Wiley. ISBN 978-0813826301. Retrieved 28 January 2018 – via Booksgoogle.com.
2. David D (January 1971). "Preparation of the Reduced Forms of Vitamin B₁₂ and of Some Analogs of the Vitamin B₁₂ Coenzyme Containing a Cobalt-Carbon Bond". In McCormick DB, Wright LD (eds.). Vitamins and Coenzymes. Methods in Enzymology. Vol. 18. Academic Press. pp. 34–54. doi:10.1016/S0076-6879(71)18006-8. ISBN 9780121818821.
3. Sil A, Kumar H, Mondal RD, Anand SS, Ghosal A, Datta A, Sawant SV, Kapatkar V, Kadhe G, Rao S (July 2018). "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. doi:10.3344/kjp.2018.31.3.183. PMC 6037815. PMID 30013732.
4. "Eisai Submits New Drug Application for Mecobalamin Ultra-High Dose Preparation as Treatment for Amyotrophic Lateral Sclerosis in Japan" (PDF). Eisai.com. Retrieved 28 January 2018.
5. Kim J, Hannibal L, Gherasim C, Jacobsen DW, Banerjee R (November 2009). "A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins". The Journal of Biological Chemistry. 284 (48): 33418–33424. doi:10.1074/jbc.M109.057877. PMC 2785186. PMID 19801555.
6. Hannibal L, Kim J, Brasch NE, Wang S, Rosenblatt DS, Banerjee R, Jacobsen DW (August 2009). "Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product". Molecular Genetics and Metabolism. 97 (4): 260–266. doi:10.1016/j.ymgme.2009.04.005. PMC 2709701. PMID 19447654.
7. Froese DS, Gravel RA (November 2010). "Genetic disorders of vitamin B₁₂ metabolism: eight complementation groups–eight genes". Expert Reviews in Molecular Medicine. 12: e37. doi:10.1017/S1462399410001651. PMC 2995210. PMID 21114891.
8. Thakkar K, Billa G (January 2015). "Treatment of vitamin B12 deficiency – Methylcobalamine? Cyancobalamine? Hydroxocobalamin? – clearing the confusion". European Journal of Clinical Nutrition. 69 (1): 1–2. doi:10.1038/ejcn.2014.165. PMID 25117994.
9. Fontecilla-Camps JC, Amara P, Cavazza C, Nicolet Y, Volbeda A (August 2009). "Structure-function relationships of anaerobic gas-processing metalloenzymes". Nature. 460 (7257): 814–822. Bibcode:2009Natur.460..814F. doi:10.1038/nature08299. PMID 19675641. S2CID 4421420.
10. Schneider Z, Stroiński A (1987), Comprehensive B12: Chemistry, Biochemistry, Nutrition, Ecology, Medicine, Walter de Gruyter, ISBN 978-3110082395
11. Bémeur C, Montgomery JA, Butterworth RF (2011). "Vitamins Deficiencies and Brain Function". In Blass JP (ed.). Neurochemical Mechanisms in Disease. Advances in Neurobiology. Vol. 1. pp. 103-124 (112). doi:10.1007/978-1-4419-7104-3_4. ISBN 978-1-4419-7103-6.