New Atmosphere, New Vision: Gibson and Whittemore Kick Off Invest in ME Conference 2016
Mark Berry reports on Dr. Gibson's introduction and Dr. Whittemore's keynote speech, at the 11th Invest in ME International ME Conference in London.
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CBS+ and CTH+ combination (or any CTH info!)

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by nimo, Nov 11, 2014.

  1. nimo

    nimo

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    Hi, I’d be very interested if anyone has any insight into how the CTH S4031I gene variant affects the transsulfuration pathway, and if it changes the advice on dealing with CBS.

    CTH appears to code for cystathionase (cystathionine gamma-lyase), which appears to sit below CBS – between cystathionine and cysteine+alpha-ketobutyrate. I don’t know if it comes before or after ammonia (I think I have seen it in either position, depending on source). I am picturing a bottleneck effect with CBS sped up and CTH slowed down (I assume CTH is slowed down as SNPedia has the +/+ genotype as causing “significantly higher plasma total homocysteine concentration” http://www.snpedia.com/index.php/Rs1021737).

    I’ve done a forum search and not found any discussion of CTH impact.

    My SNPs are CBS C699T +/+ , CTH S4031I +/+

    Many thanks

    Nick
     
  2. Valentijn

    Valentijn The Diabolic Logic

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    The CBS version is pretty irrelevant - it has a tiny effect.

    But the CTH mutation (rs1021737) can cause elevated homocysteine: http://www.omim.org/entry/607657#0005 . The research is published at http://onlinelibrary.wiley.com/doi/10.1111/j.1399-0004.2004.00250.x/abstract but only the abstract is free.

    It's possible that the effect size for rs1021737 is also tiny, but it's very possible that it has a big effect. A Serine (S) amino acid is being replaced with Isoleucine (I) - and those two amino acids behave VERY differently.

    I'm going to try to get my hands on that study, to see what the effect size is.

    At any rate, CTH needs B6 to function, so it might help to supplement a normal amount of that. High doses or even borderline high doses can result in toxicity.
     
  3. Valentijn

    Valentijn The Diabolic Logic

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    Gondwanaland likes this.
  4. Gondwanaland

    Gondwanaland Senior Member

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    @nimo for 3-letter words like CTH you've got to click the google search option, you might get a few results from previous posts/topic here at the board.
     
  5. nimo

    nimo

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    Hi Valentijn. Thanks for the reply. Would you mind explaing the above? I thought CBS C699T was the major player in CBS issues (CBS A360A the minor player), and CBS issues having a major effect in draining the methylation cycle.

    Edit: Am reading the article, will reply to the rest of your post after!
     
    Last edited: Nov 11, 2014
  6. nimo

    nimo

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    Thanks Gondwanaland. I thought I'd done the Google search, but did it again and found some useful info, including two useful looking presentations by Rich (more general info, than specific to CTH):

    http://phoenixrising.me/wp-content/uploads/MethylationPPP.ppt
    http://phoenixrising.me/wp-content/uploads/IAOMT_talks_Rich_Van_K._2011__Part_1R.pdf
     
    Last edited: Nov 11, 2014
  7. nimo

    nimo

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  8. Valentijn

    Valentijn The Diabolic Logic

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    No, CBS C699T +/+ is a very minor upregulation, and generally a beneficial one. Yasko is not capable of accurately interpreting the studies regarding it, however. She makes rather bizarre claims based on unrelated research - basically equating C699T +/+ with having half of the gene chopped off.

    More discussion of it is at http://forums.phoenixrising.me/index.php?threads/couple-of-questions.22718/ , primarily in the posts by @dbkita .
     
  9. nimo

    nimo

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    Thank you for that link. I thought I'd read enough forum posts and other sources to see a spread of views, but I haven't before seen anything to counter Yasko's 5-10x assertion. From that thread:
    The quoted 1.1x may still be an issue for me. I think I do have ammonia and sulfur compound issues as I can smell sulfur in urine and ammonia in sweat. I know not the sulfite quoted above, but sulfate strips arrive today so I'm hoping they're useful enough to give me a clearer picture. I am also thinking of other functional tests - Nutreval and Methylation Pathway.
    Thank you. I often find that searching for paywalled papers will find a legitimate free-to-access copy. I now have it in Mendeley. An issue that I have not seen before is the possible inhibition of MAT (in methionine -> SAMe conversion) by cystathionine i.e. further back in the cycle. As they say in the study, it would have been nice to correlate cystathionine levels with their data.
    I have some 50mg P5P caps (which I think I'd split initially), which I have been dithering about taking as I am thinking of functional testing (I have asked the forum about which supplements to be on at time of testing in another post: http://forums.phoenixrising.me/inde...on-or-off-supplements-when.33720/#post-522353)
     

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