Lots of people are sensitive to B6 - there could be several reasons for this but it is not because you have some SNP which is upregulating CBS.
All the SNPs known to have significant effects on activity of the CBS enzyme are downregulations. A couple of the more well known ones are mentioned in the GPL quote.
There is no research supporting the two said to be upregulations, nor would you expect them to have any real effect since they result in no change to the protein product. The enzyme produced by the variant is identical to that produced by the wildtype gene.
There is another SNP not mentioned in that quote, rs234706 AKA C699T, which is usually the one claimed to result in dramatic upregulation. This claim is wildly exaggerated and is based on a complete misreading and misinterpretation of research unrelated to the SNP. There are a couple of studies which suggest there might be a slight upregulation associated with this SNP but this appears to be protective, since it slightly lowers homocysteine.
Other studies though have not reproduced this so it may be a study error. Again this SNP causes no change to the enzyme, so the explanation for the observed effects, if real, may lie elsewhere.
Here is a
thread discussing CBS.
The quote in your second post is just fudging it. There are indeed multiple influences on CBS activity but, as already explained, not upregulating SNPs, nor has B6 been described as a significant regulator of the enzyme.
Of course if B6 were deficient, enzyme activity might be slowed and so addressing the deficiency might stimulate the enzyme. In cases of known genetic defects producing an enzyme with very reduced activity, very high doses of its cofactor B6 can sometimes stimulate the defective enzyme.
These genetic defects are very rare and not I suspect what the author is referring to.
In any case you were taking quite a small dose of B6 - this in itself would have little influence on CBS.
You seem to be confused about what CBS does and how this affects homocysteine. CBS is the first enzyme in a pathway which converts homocysteine to cysteine and then to a variety of other products depending on cellular needs. One of the most important of these is the master antioxidant glutathione (GSH). Need for GSH is one of the important upregulators of CBS activity.
High CBS activity means that more homocysteine is converted to cysteine and so homocysteine levels will be lower.
Low CBS activity means that less homocysteine is converted to cysteine and so homocysteine levels will be higher.
In your own case your homocysteine is in the normal range. This gives no clues to what is happening with CBS.
The elevated 2 hydroxy butyric acid does indicate increased flux through the pathway. Perhaps you are under oxidative stress and your needs for GSH have increased.
You say you have high methionine. This could be another reason for increased flux through CBS.
Homocysteine can follow two pathways. It can remain in the methylation cycle and be remethylated to methionine by the action of the enzyme methionine synthase (B12 dependant), which in turn is dependant on the enzyme MTHFR to supply methylfolate which is the ultimate methyl donor in the reaction. The enzyme BHMT also carries out the same conversion but using betaine as the methyl donor rather than methyl folate.
Alternatively homocysteine can exit the methylation cycle via the action of CBS and be used to make GSH and other things.
The other important regulator of the balance of these two pathways is the universal methyl donor S adenosyl methionine (SAM) which is derived from methionine. When methionine is high (eg after a protein rich meal), SAM is high. This stimulates CBS to remove homocysteine so levels of SAM don't become too high. In addition, SAM inhibits MTHFR and BHMT to slow down formation of methionine and again prevent SAM getting too high.
As SAM falls, CBS slows down so less homocysteine exits the methylation cycle and MTHFR and BHMT speed up so more homocysteine is converted to methionine.
The normal overall balance in the cell is about 50:50 between the two pathways, but there is considerable variation in this balance depending on cellular need.
Your results could just reflect things like a high protein diet and an increased need for antioxidants.
