The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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  1. humptydumpty

    humptydumpty

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    Hi Everyone, I don't have CFS, but got attracted to this forum by high quality posts. I would to learn more about glutathione, how it is produced and recycled.

    A few months ago I ran a spectracell micronutrient tests which told me I am desperately low in antioxidant function. I was supposed to supplement NAC among others, but I actually started with reduced glutathione with good results, some health problems resolved. After learning that glutathione is actually hydrolized to the three constituent amino acids on digestion, and getting additional glutamate might a be a bad idea, I switched to NAC. I also saw someone saying to supplement glutamine and glycine and rely on homocysteine for cysteine. I have elevated homocysteine so that rings true. Where can I learn more about this?

    I would also like to find out why would glutathione be low with high homocysteine at the same time and CBS upregulation (lack of some substrates/co-factors?).
     
  2. Valentijn

    Valentijn Senior Member

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    The CBS gene is responsible for converting homocysteine back into cysteine, which then hooks up to form glutathione. If the gene were downregulated, homocysteine could be high and glutathione low. Additionally, insufficient B12 or methylfolate also might be slowing things down.

    B6 supplementation would help in converting homocysteine into cysteine, and B12 and/or methylfolate might help in keeping things moving and lowering homocysteine.
     
  3. humptydumpty

    humptydumpty

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    Assuming high homocysteine, why would insufficient b12 or methylfolate be slowing things down for glutathione synthesis?

    Does anyone have a link with the glutathione pathways well modeled. Like what are the enzymes regulations and substrates? Maybe that is not well understood yet though.
     
  4. Valentijn

    Valentijn Senior Member

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    Reactions in the methylation cycle generally can run in two directions. There might be a problem with things running a bit in the wrong direction, and supplementing might help with that.

    If you look for "methylation" at google images, you should be able to find something showing both methylation and the pathway from homocysteine into cysteine and maybe all the way to glutathione.
     
  5. humptydumpty

    humptydumpty

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    I understand that some reactions can flow both directions, but I don't understand how does that answer my question. Can you be more specific?
     
  6. Valentijn

    Valentijn Senior Member

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    Sorry, no. It's not an area I've really looked into.
     
  7. PeterPositive

    PeterPositive Senior Member

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    I think the main problem is that with insufficient B12 and folate the cycle either slows down or gets stuck and it's no longer driving the glutathione production (and SAMe) at the end of the chain.

    B12 and folate are necessary to re-methylate homocysteine and keep the "wheel turning", if it slows down too much the trans-sulfuration pathway will also be affected.

    I think Rich Von Konynenburg explained this pretty well in this article:
     

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