MeB12 can donate methyl groups to DNA when SAMe is absent

As a continuation of the “challenging the common wisdom” post - I should have read the referred paper till the end, because it mentions the direct effect of meB12 on methyltransferases:

“It has been an issue whether pharmacological doses of MeCbl can act as a nonspecific methyl donor or an effector of other methylation processes than the conversion of homocysteine to methionine.

In vitro, methyl groups from MeCbl are incorporated into DNA via DNA-methyltransferase (from rat spleen) when SAM is absent.

In the presence of SAM (which is abundant in the physiological milieu), also AdoCbl and CNCbl increase DNA-methylation by methyltransferase, though MeCbl is the most efficient compound.

Thus, it appears that the role of MeCbl as a universal direct methyl donor in vivo is uncertain because SAM and GSH are abundant in the cell.” (R1)

This is interesting because of two things:

1. Use of adoCbl and CNCbl for methylation purposes depends on SAMe - because we already know that MMACHC removes all groups from cobalamin, which then later receives methyl from SAMe before being attached to MS enzyme. So when SAMe is lowered, production of new methylB12 from non methylB12 is impaired.

2. It seems methylB12 can donate methyl groups to methyltransferases instead of SAMe when the latter is low.

Next, the paper refers to another study (R2).

There are some interesting findings in it, potentially changing our understanding upside down (I simplified the abstract and added my notes in <…>):

5-Methylcytosine synthesis in DNA involves the transfer of methyl groups from SAMe to the 5'-position of cytosine through the action of DNA (cytosine-5)-methyltransferase.

The rate of this reaction has been found to be enhanced by cobalt ions.

We therefore analyzed the influence of vitamin B12 and related compounds containing cobalt on DNA methylation.

Methylcobalamin was found to enhance significantly the de novo DNA methylation in the presence of SAM for concentrations up to 1 microM, but at higher concentrations these compounds were found to inhibit DNA methylation.

Methylcobalamin behaves as a competitive inhibitor of the enzymatic methylation reaction (Ki = 15 microM), the Km for S-adenosylmethionine being 8 microM."

Do you see the provocative finding here? High concentration of methylB12 inhibits DNA methylation, which in general means genes will not silenced.

Could THIS be the actual benefit we’re looking for? I have heard opinions that DNA methylation is what we need, but I don’t think it’s that simple - I would rather prefer a proper work in methylation/acetylation/whatnot.