Hi, AQG.
What's important for having good methylation function is to have a high enough level of SAMe and a high enough ratio of SAMe to SAH (though not too high, and this is usually taken care of by the glycine N-methyltransferase reaction, which uses excess SAMe to convert glycine to sarcosine).
If SAH rises, it lowers the ratio of SAMe to SAH, and that slows most of the methylation reactions in the cells.
A rise in SAH suggests that there is a bottleneck downstream of it at methionine synthase. A rise in SAH implies that there is also a rise in homocysteine, because there is an equilibrium reaction between them, involving the AHCY enzyme. The equilibrium is shifted toward SAH, so when methionine synthase is partially blocked, the rise in homocysteine causes a rise in SAH.
Now, whether a given person who has a partial block of methionine synthase will also have SAH above its reference range will depend on some other things. One is their methionine status, because methionine is what feeds the methylation cycle. If methionine is normal or high, it is more likely that SAH will be high. However, the SAH level will also depend on what polymorphisms are present in AHCY and CBS. CBS enzymes will tend to drain homocysteine into the transsulfuration pathway, and that will tend to lower SAH. I'm not sure which direction the AHCY polymorphisms will move SAH, but they will likely have some effect also.
So it isn't all that straightforward, but I think this combination of things is what is involved.
Best regards,
Rich
