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Ampk dysfunction and ME/CFS

Frenchguy

Senior Member
Messages
119
Location
France
Interesting,

I just read Fluge's study on the impaired pyruvate dehydrogenase function and they found that PDK1, PDK2 and PDK4 RNA are elevated.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/

Pyruvate dehydrogenase kinase or PDK' is a class of enzymes that inhibit pyruvate dehydrogenase.

"PDK1–PDK4 are regulated at the transcriptional level via signaling cues involving factors such as AMP-dependent protein kinase (AMPK) (22), PPARs (23), and HIF1 (24)."

The AMPK enzyme is directly related to PDK '

If the mysterious factor in the serum was an enzyme (AMPK or an other) ?

If I remember correctly, Ron Davis said it was probably a protein which cause the increase of impedance. An enzyme is a protein.

I don't know if it's possible to just test the buffy coat to see if lymphocytes or monocytes can be implicated in the rise of impedance.

For me, we may well have an dysfunctional (I don't like this term) enzyme that causes all our problems. But which ? For which subgroup?
 
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Frenchguy

Senior Member
Messages
119
Location
France
I wanted to give you some info relevant to this Thread.

CC : @perrier @Hip

1. Snapshot from the document i sent to several ME/CFS Researchers in October 2017 :


View attachment 27396
Please Note : AMPK is associated with Autophagy.


2. From the Wikipedia Entry of AMPK we read :



Regarding PGC-1a aka PPARG1a, from February 8, 2016, Phoenix Rising :


https://forums.phoenixrising.me/ind...e-treatment-for-cfs.37244/page-70#post-694400

Special cc : @perrier , PGC1a is associated with NRF1

https://en.wikipedia.org/wiki/PPARGC1A

Also we have the following entry from Wikipedia :



Please note the word Glucokinase. From the same doument we read :

View attachment 27398


Given the above, please search PR and you will find many mentions regarding Thiamine and Biotin having positive effects to ME/CFS Patients.

Finally you can see Network Analysis identifying Pgc1 as well which is also included to the document i circulated (Right from Urea_Cycle node):

index.php


Looking forward to your comments.

Thanks Mario,

It's interesting. I looked many posts where people take thiamine or biotin.

Only few report modestes improvements.

This may be the cause for a very small subset who know.

When Davis said that there is a similar mechanism which keep us in this f.c.i.g state, I think that he is right.
When you see the numbers of topics on people say they take X or Y supplement and the numbers of people in remission or cured (nobody know if they had ME/CFS), the people who take combo supplement, I don't think the response will be a supplement or a vitamin.

Enzyme control all our functions and I hope they are right.
 

mariovitali

Senior Member
Messages
1,212
@Frenchguy

I know 4 people that got Symptom-free using Supplements (this includes myself), one of them is cured (ie receives no supplements to this day). I already sent to Dr Davis and Dr Phair this person's DNA Data.

My understanding is that -according to Dr Davis -ME/CFS Patients will be able to overcome their problem without Medication. If this is so what else could achieve such cure?

Regarding Thiamine and Biotin : It depends how much they help according to the combination of issues that an individual has. We need to give a very precise combination of Supplements and avoidance of specific types of food (=Personalised Regimen)

Another question that still exists is how many ME/CFS Patients have also Liver / Gallbladder issues that are undiagnosed : These issues include Hemochromatosis, Wilson's Disease, NAFLD, Cholecystectomy, Cholestasis, Autoimmune Hepatitis, Liver Fiobrosis and many more.

I highly doubt that a "Metabolic Trap" would make patients having these issues cured in the long run without identifying and correcting a more central issue. There is also a number of ME/CFS Patients that had Liver issues for many years before having ME/CFS. I believe that the Metabolic Trap is non-applicable to them in the long run.

Please don't get me wrong : Like any other patient i look forward to Dr Davis findings and hope for the best.
 
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pattismith

Senior Member
Messages
3,905
Top athletes are doping for some (not a surprise).

AICAR is used to over-activate AMPK. This over-activation makes it possible to maintain the effort longer but especially to recover more quickly.

https://extremepeptides.com/product/aica-ribonucleotide-aicar-50mg/

AICAR is a direct AMPK activator, I don't know if this way to activate AMPK is clean.

I am interested in this one, did you try it?



Isoeugenol seems interesting too:

"Isoeugenol (4-propenyl-2-methoxyphenol) is a naturally occurring o-methoxyphenol and a clear to pale yellow oily liquid present in various foods and essential oils, especially clove oil and cinnamon (Choi et al. 2007, Salanti et al. 2010)

...
AMPK activation requires the phosphorylation of a catalytic α subunit at Thr-172 in its activation loop (Crute et al. 1998, Stein et al. 2000). Both liver kinase B1 (LKB1) and calcium/calmodulin-dependent protein kinase kinase (CaMKK) are involved in AMPK activation (Hawley et al. 2003, Woods et al. 2003, Hong et al. 2005, Hurley et al. 2005). AMPK plays a pivotal role in glucose uptake in an insulin-independent manner. In vitro studies have shown that isolated muscles exposed to 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) show increased glucose uptake in the absence of insulin (Hayashi et al. 1998, Bergeron et al. 1999, Koistinen et al. 2003). Therefore, it can be suggested that isoeugenol-induced AMPK activation is a promising target for regulating glucose uptake in an insulin-independent manner. However, not many candidates have been identified as successful antidiabetic agents thus far.
In this study, we investigated the effects of isoeugenol on AMPK phosphorylation in the muscles to precisely characterize its metabolic effects. We observed that isoeugenol increased AMPK phosphorylation and glucose uptake through p38 MAPK and AS 160 pathways."
 

pattismith

Senior Member
Messages
3,905
AICAR (= ZMP) is an analog of adenosine monophosphate (AMP) that is capable of stimulating AMP-dependent protein kinase (AMPK) activity. The drug has also been shown as a potential treatment for diabetes by increasing the metabolic activity of tissues by changing the physical composition of muscle. (wikipedia)

Low-Dose Methotrexate Results in the Selective Accumulation of Aminoimidazole Carboxamide Ribotide in an Erythroblastoid Cell Line​

Selective toxicity toward T cells and activation of AMP-activated protein kinase by ZMP has also been proposed as mechanisms of activity of MTX in autoimmune disorders

jpet.113.206672f1.jpg


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781408/