Friday, 9 February 2018

leucine restriction for IDH1mut?

Hi all,

This article here says that leucine is an activator of GLUD2.

http://www.pnas.org/content/111/39/14217

This is the article they sited:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944346/

Leucine is an essential amino acid, which means we must eat it in order to get it. The first article seems to say that leucine is stored in IDH1 mutant gliomas…but I read another article that this depends on the concentrations of ADP and L-Leucine — which implies they can be diluted. Is there an ADP inhibitor? (An initial google search seems to say there is but I'm not sure how they will impact the brain or health in general. I'm going to search that when I have more time.)


Thanks.
Maria

5 comments:

  1. ADP is one of the most fundamental molecules in living cells.
    https://en.wikipedia.org/wiki/Adenosine_diphosphate

    ATP is the "energy currency" of the cell and is constantly formed from ADP.

    Doesn't seem to me that tinkering with such important systems would be that safe, even if it were possible.

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  2. Yea, I was thinking that. But there are inhibitors to prevent blood clotting I guess. Aspirin was one of them...which is interesting since Ben W. took that too. I’m not sure how that would impact the brain though.

    Either way, what about leucine? I was more interested in that.

    Thank you!

    Maria

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    1. What we have here is a hypothesis: that restricting leucine would impair activity of GLUD2 and the growth of IDH-mutant gliomas.

      The problem with testing this hypothesis is that the body has a non-negotiable requirement for leucine as an essential amino acid, and it would also be difficult to limit leucine without limiting overall protein intake. You would have to know the specific amino acid content of every dietary item and be doing mathematical calulations at every meal to ensure baseline needs for essential amino acids were being met, otherwise risking protein deficiency. This sort of thing is much easier to experiment with in mice, who are fed a formula where the amino acid content is known and much easier to manipulate and control.

      My conclusions would be: an experiment in limiting an essential amino acid would be quite complicated to implement and the outcome would be uncertain, given the lack of preclinical evidence that limiting this nutrient to its minimal daily requirement (without creating a protein deficiency) would indeed slow the growth of these tumors.

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  3. Yes. That’s all true. The ketogenic diet limits protein and I’m trying to decipher whether leucine is more abundant in lean muscle meats that fatty meats...but I haven’t found clarity there yet. But, others have said, it’s a ketogenic amino acid. I wonder what that would mean? Thank you, Stephen.

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    1. A keto amino acid means it is used by the liver to produce ketones (as opposed to others that are used to produce glucose). Leucine and lysine are the keto amino acids. I have a book that limits protein to 8-12% and there is an app that tracks all of your dietary intake, including your amino acids. Called something like chronometer. I think I’ll try to incorporate a low protein/leucine diet into my ketogenic regimen. Not cutting it out completely. Of course it’s just a guess but who knows, right? I was a vegan for a number of years, so I’m a bit accustomed to tracking protein.

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