nandixon
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... and secondly, any symptoms which people are currently reporting as being 'folinic acid intolerance' might just as easily be overmethylation (which suggests the dietary folates are being processed just fine and so are contributing to the methylation cycle along with the existing methylfolates?)
I don't think folinic acid would likely be causing over-methylation. It's an inhibitor of SHMT, the enzyme that makes methylene-THF which is the substrate methylenetetrahydrofolate reductase (MTHFR) converts into 5-methyltetrahydrofolate (methylfolate) for use in the methylation cycle. (Less methylene-THF means less methylfolate.)
That's why I was speculating early in this thread that perhaps defects in both MTHFS and SHMT together might possibly cause a folinic acid intolerance problem. (A defective MTHFS causing a buildup of folinic acid that might in turn cause a defective SHMT to be more inhibited than it might otherwise would be.) There are lots of other possibilities for an intolerance, though.
Whilst on this point I just want to clarify my understanding of dietary folates to date because it seems to cause an awful lot of confusion as to how they're processed. DBKita suggests that vegetables contain a bunch of THF's that are packed into polyglutamates.
The "bunch of THF's" apparently include primarily methylfolate and 5-formyltetrahydrofolate (folinic acid) in polyglutamated forms (and I think 10-formyltetrahydrofolate and some others).
Tying this in with Lotus97's input: the SHTM1 related enzyme does the first stage of processing the THF to a DHF and then MTHF677 does the rest through its relation to the DHFR enzyme which converts the Dihidrofolate to methylfolate? Is this correct?
SHMT converts THF to methylene-THF (which is not a DHF) as mentioned above. MTHFR then converts methylene-THF to methylfolate.
I think DHFR primarily comes into play with respect to the synthesis of methylfolate if one is taking the synthetic folate, folic acid.
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