I’ve discussed the two recycling pathways of Homocysteine using MTR and BHMT, as well as the clearance pathway via the transsulfuration pathway and the CBS enzyme. In this post, I’ll discuss a fourth pathway or fate of Homocysteine that may be one of the most over looked fates of Homocysteine, yet can have the potentially greatest impact on our health.
The pathway I’m referring to is the reverse pathway from where Homocysteine came from. Homocysteine once recycled via MTR or BHMT is converted to Methionine. Methionine is then converted to SAM VAA the MAT enzyme. SAM than participates in a Methylation reaction giving up its methyl group and becomes s-adenosylhomocysteine (SAH). SAH is than rapidly converted to Homocysteine and Adenosine via the enzyme (AHCY).
However, the Thermodynamic Equilibrium reaction catalyzed by AHCY favors the reverse reaction of Homocysteine and Adenosine making SAH. Meaning, that SAH is a more sensitive marker for vascular inflammation than HCY. HCY could appear normal and yet SAH be elevated due to the favor of the RXN back toward SAH.
So in this situation as Homocysteine levels build, the flow HCY will be back towards SAH, especially if there are hormones in the recycling or clearance pathways. Research has shown that when HCY is high there will be HIGH SAH as well.
Interestingly, lowering of HCY does not necessarily correlate with lowering of SAH. Which is why, lowering HCY with vitamins doesn’t necessarily correlate with decreased vascular events. You can lower your HCY by supporting the three other pathways but that does not mean you’ve lowered SAH.
SAH could still be elevated due to AHCY SNP’s, NAD deficiency or elevated levels of Adenosine. High levels of Adenosine would inhibit the forward reaction.
That leaves us with the question of what is causing elevations of Adenosine. That will need to be left to my blog post.
I’ll finish this post with the problem of elevated SAH. When SAH is elevated, SAH inhibits SAM reactions. SAH can preferentially blind in place of SAM. The loss of SAM methylated reactions sets the stage for systemic dysfunction, inflammation, and regeneration.