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. Methylcobalamin features an octahedral cobalt(III) centre and can be obtained as bright red crystals. 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 can be produced in the laboratory by reducing cyanocobalamin with sodium borohydride in alkaline solution, followed by the addition of methyl iodide.

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.

Methylcobalamin is produced by some bacteria. 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. In this role, methylcobalamin serves as a source of "CH₃".

Role in human health

Methylcobalamin is equivalent physiologically to vitamin B₁₂, 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.

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.

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.