alex3619
Senior Member
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Hi Annesse, its is not proven that low glutathione does not lead to low neurotransmitters and hormones. In particular if the substance is a protein (some are) or if the substance requires a protein for synthesis or regulation (all do) then its dependent on correct functioning of that substance. Now glutathione is required for correct folding of very many proteins - and the larger the protein the higher the chance of this. If you were to assay these proteins, you would get normal or even high levels, despite that their functional capacity was decreased. I would be interested in other studies on glutathione depletion, to find out the neurotransmitter levels. From what I read of your commentary, your evidence backs glutathione being important this way.
I am very concerned about this for aconitase: let me use that as an example. Aconitase is not made by the mitochondria. It is a cell protein. It starts unfolded, and at some point has to be folded into its correct shape. I do not know if this is prior or after it enters the mitochondria - I suspect prior as the cell has extensive protein modification machinery. Glutathione is one of the substances used to do this folding by helping to create sulphide bridges. Once it has entered the mitochondria and is located correctly it can begin to convert citric acid. If its not folded correctly it can't. However, it also can't be shown to be deficient - there can be plenty of aconitase about, it just doesn't work if not folded. This might induce the cell to make more, and even more, leading to high aconitase levels, I don't know for sure - it would be interesting if someone could show elevated intracellular aconitase. That might be a sign of functional deficiency. Similarly high aconitase production might lead to higher protease synthesis to degrade the unfolded aconitase.
So in other words its an open question. You could be completely right, or partially right, or mostly wrong. We don't know yet. The only way we can tackle open questions is to do more research. That is why I am interested in your model.
On the relevance of established pathways, I discuss this in my blog on ME models:
http://forums.phoenixrising.me/entry.php?1272-Issues-with-ME-Models
Simply using existing pathways, or supected pathways (unconfirmed, hypotheses, etc) is only rung one.
Bye,
Alex
I am very concerned about this for aconitase: let me use that as an example. Aconitase is not made by the mitochondria. It is a cell protein. It starts unfolded, and at some point has to be folded into its correct shape. I do not know if this is prior or after it enters the mitochondria - I suspect prior as the cell has extensive protein modification machinery. Glutathione is one of the substances used to do this folding by helping to create sulphide bridges. Once it has entered the mitochondria and is located correctly it can begin to convert citric acid. If its not folded correctly it can't. However, it also can't be shown to be deficient - there can be plenty of aconitase about, it just doesn't work if not folded. This might induce the cell to make more, and even more, leading to high aconitase levels, I don't know for sure - it would be interesting if someone could show elevated intracellular aconitase. That might be a sign of functional deficiency. Similarly high aconitase production might lead to higher protease synthesis to degrade the unfolded aconitase.
So in other words its an open question. You could be completely right, or partially right, or mostly wrong. We don't know yet. The only way we can tackle open questions is to do more research. That is why I am interested in your model.
On the relevance of established pathways, I discuss this in my blog on ME models:
http://forums.phoenixrising.me/entry.php?1272-Issues-with-ME-Models
Simply using existing pathways, or supected pathways (unconfirmed, hypotheses, etc) is only rung one.
Bye,
Alex