What happens to the methyl component when methylcobalamin breaks down, whether in a vial or after injection?

[EllieMayNot]

Trying to get a better grasp on how methylcobalamin "works". I have read that, since methylcobalamin is so unstable, often when what we think we are injecting is methylcobalamin is essentially hydroxocobalamin. What happens to the methyl component either in the vial during the degradation process or in the body during biological processes?

[fbirder]

In the vial the process of chemical breakdown is likely to produce methanol.

In the body the same is most likely to happen. But the methanol will be further oxidised to methanal (formaldehyde) then methanoic acid (formic acid) then carbon dioxide.

But, in each case the amount of methanol produced will be tiny. 1000 mcg of methylcobalamin will produce about 0.3 mcg of methanol.

To put this into context - a litre of wine is allowed to contain anything up to 400,000 mcg of methanol. You would need one million methylcobalamin injections to get that much.

[Gambit62 Administrator]

I'm not clear what the other products of the breakdown of methylcobalamin are - they may include hydroxocobolamin but they may also include other forms of cobalamin which are not biologically accessible so I wouldn't assume that if the methyl is old that it is just another useful form of cobalamin in the file.

[fbirder in reply to Gambit62]

There's not a lot in a solution of methylcobalamin that it could react with. Hydrogen ions and hydroxide ions are there in the highest amounts along with smaller amounts of acetate ions.

Acetocobalamin is used as another name for hydroxocobalamin in some preparations, so it must react with hydroxide ions.

I cannot find anything about a form of cobalamin with hydrogen as the top ligands, so I assume it's unstable in the presence of hydroxocobalamin.

I cannot think of anything else it might react with.

While stuck in a traffic jam (somebody decided to drive a tractor into the village's power line) I had a rethink of what I can remember about coordination chemistry from more than 20 years ago. I was wrong that cobalamin might react with hydrogen ions. It will only react with neutral, electron-rich, molecules, and negative ions (like OH- and CH3COO-) but not positive ions (like H+).

So it can form hydroxocobalamin, aquocobalamin and acetocobalamin (which soon converts to hydroxocobalamin).