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I actually prefer Heartfixer to Yasko's explanations but there is generally less info out there on these 2 compared with mthfr.
mthfr1298, BHMT, MTHFS, CBS
I am wondering what knock on effect there may be from MTR/MTRR to BH4 production
As I mentioned in the TMG thread, severe brain fog is my worst sx. By trial and error it seems to be high ammonia. Clinical liver disease isn't apparent so I am left with hypotheses from my SNPs. I have treated and am managing my gut health for infections and overgrowth. Because I struggle to believe my MTHFR or CBS SNPs are behind this, I wondered if MTR/MTRR could be indirectly affecting my ability to keep ammonia (& to a lesser degree, sulphur) under control. According to some source I can't recall if was HF, BH4 is prioritized to ammonia over neurotransmitters. I always get depression & anxiety with these severe fog/vertigo days & weeks.I can't think of anything in particular, it would have to be something indirect. Is there some particular aspect you have in mind?
I struggle to believe my MTHFR or CBS SNPs are behind this
According to some source I can't recall if was HF, BH4 is prioritized to ammonia over neurotransmitters
the fog improves with 2x daily lactulose
How to fix this? I've been treated for dientamoeba twice, with metronidazole then doxycyline. This was post-2012. No sxs of dientamoeba now but still get the fog. Herbalist has put me through 2mths of wormwood Treatment, first week I thought I was dying (the 'ammonia' sx I assumed from dead microbes). Have done body ecology, gaps, low FODMAPS. My gut issues preceded ME, really don't know the answer. Take probiotics, am a mess without them, but I'm convinced no one really knows which and how many strains are best!microbes which can ferment amino acids, in turn releasing ammonia as a by-product
but I'm convinced no one really knows which and how many strains are best!
How to fix this? I've been treated for dientamoeba twice, with metronidazole then doxycyline. This was post-2012. No sxs of dientamoeba now but still get the fog. Herbalist has put me through 2mths of wormwood Treatment, first week I thought I was dying (the 'ammonia' sx I assumed from dead microbes). Have done body ecology, gaps, low FODMAPS. My gut issues preceded ME, really don't know the answer. Take probiotics, am a mess without them, but I'm convinced no one really knows which and how many strains are best!
I wondered if it (poor gut flora) goes back to poor immune function that in part is affected by methylation and/or toxicity. That parasite apparently does not normally become pathogenic in healthy adults. Obviously not many of us here are healthy!
Suggesting the ammonia source is the gut. This need not be anything pathological, just a preponderance of microbes which can ferment amino acids, in turn releasing ammonia as a by-product (for example - there could be other explanations).
I am wondering what knock on effect there may be from MTR/MTRR to BH4 production but brain bout to explode from this mornings chemistry lesson
Folate appears to be important in regenerating BH4, which is highly susceptible to oxidation. The folate-metabolizing enzyme dihydrofolate reductase might also be involved in BH4 regeneration.36 Other research suggests folate is necessary as a starting material for pterin synthesis and this may be the focus of the folate/BH4 relationship (Figure 4).34
This paper/article seems to contain the answer
It has been demonstrated that folate, in the
form of 5-MTHF, regenerates oxidized BH4,37 and in
the absence of an adequate amount of BH4, 5-MTHF
“stands in” for BH4 at the enzyme level.38
Is it possible that high dose 5MTHF will "free up" more of DHFR so that is can recycle more BH4 instead of generating 5MTHF?BH2 can be regenerated to BH4 by the enzyme DHFR
Is it possible that high dose 5MTHF will "free up" more of DHFR so that is can recycle more BH4 instead of generating 5MTHF?
Thanks, that totally make sense.MeTHF is an inhibitor of DHFR so I don't think that mechanism would apply.
However MeTHF is a potent peroxynitrile scavenger so acts to spare BH4.
lets say that DHFR works at max rate on BH4 recyling @ 50 reactions per second and the same for 5MTHF.
I was assuming that if MeTHF was in excess then also THF would be, and in that case DHFR would be inhibited by the THF as you say. Of course I didn't realise that THF could be used for things beside making MeTHF. However assuming that you took enough MeTHF, enough would recycle back to THF then go down those pathways until they have enough THF and say we don't need anymore and inhibit DHFR.I'm not sure what you mean by "and the same for 5MTHF". DHFR doesn't produce MeTHF, it produces THF. The latter does feed into the folate cycle, one product of which is MeTHF, but there are several steps in between and several different enzyme systems operating, each of which have their own set of rate determining parameters.