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Could PEM be caused by low glycogen phosphorylase?

Discussion in 'Post-Exertional Malaise, Fatigue, and Crashes' started by Kimsie, Dec 18, 2015.

  1. Kimsie

    Kimsie Senior Member

    Super simple version of my current thoughts on PEM.

    Glycogen phosphorylase (GF edit: this should be GP) changes glycogen to glucose for a quick source of energy. There is a form of GP in the brain that they don't know much about, except that if you don't have it you're probably dead. My hypothesis is that if a person has low GP in the brain and they use their brain for a lot of activity the brain says "Whoa! buddy, I don't have enough quick energy for this. I'm going to slow you down!" and the brain makes changes (that take a day or two to effect) that stop the person from being able to use their brain so much. The way they feel after the brain makes those changes is a crash. The changes wear off if the person doesn't use their brain too much for a while.

    More technical explanation below.

    Glycogen phosphorylase is pretty well known due to its role in helping to sustain activity in the muscles by rapidly supplying glucose during exercise, but the role of brain glycogen phosphorylase does not appear to have been explored yet. One thing that is known is that it doesn't have any loss of function mutations, which suggests that it is vital to life. Muscle GP mutations, on the other hand, are well known.

    Since GP changes glycogen to glucose for quick energy, it doesn't seem unreasonable to hypothesize that a deficiency could cause PEM.

    The hypothesis I am forming is that if a person has low brain GP their body would be likely to try to compensate through changes in genetic expression. These changes would be different in different individuals, and the symptoms would be different. I hypothesize that in people with CFS/ME the brain responds to brain activity that overreaches the ability of GP to supply the needs of the brain by instigating epigenetic changes to shut down the activity of the person, leaving them with greatly lessened ability to move and think. These epigenetic changes take a certain number of hours to effect, and the severity of the changes is in proportion to how far the activity has strained the GP needing parts of the brain.

    "In this review recent evidence has been brought forward highlighting what has been an emerging understanding in the field of brain energy metabolism: that brain glycogen is more than just a convenient way for the astrocyte to store energy for use in emergencies—it is in fact a dynamic molecule with versatile implications in normal brain function."

    I am planning to post in the general CFS/ME forum about how I think a person can become deficient in GP.
    Last edited: Dec 18, 2015
    Gondwanaland, Skippa and Dan_USAAZ like this.
  2. Bansaw

    Bansaw Senior Member

    Is there a test for low GF?
  3. Kimsie

    Kimsie Senior Member

    There is a muscle biopsy which can show the amount of muscle GF, which depending on the cause of deficiency, could be a good marker for the brain form of GF. There have been studies using muscle biopsies on people with CFS and fibro but I haven't yet found any where they looked at GF levels, although in some they remarked that glycogen levels were elevated - something that is found in McArdle disease, which is caused by a genetic inability to produce enough of the muscle form of GF.

    My guess is that a muscle biopsy for GF levels would be worth checking out in CFS/ME, but this is a new idea. I guess no one has thought of it before. I don't know how difficult it would be to get it done if McArdle disease isn't suspected.

    I just realized that GF should really be GP!
  4. hvac14400

    hvac14400 fatty & acid : )

    so there is a glycogen store in the brain? and how big it is? for some reason i think the size is close to zero grams :D
  5. Keela Too

    Keela Too Sally Burch

    Interesting idea. Can't understand how studies exploring physiological mechanisms for our post exertional problems get less traction than psyche fatigue based studies. There must be so many good ideas worth exploring.
    Mel9 likes this.

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