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Fluge and Mella Found a Pyruvate Dehydrogenase Impairment in ME/CFS: Does This Really Explain ME/CFS?
A new argument suggests pyruvate dehydrogenase (PDH) impairment may not be a candidate for the underlying cause of ME/CFS.
In Fluge and Mella's 2016 metabolomic study, they found impaired pyruvate dehydrogenase function in ME/CFS, and it has been speculated this might be the cause of the apparent energy metabolism dysfunction of this disease — a dysfunction which causes fatigue and other ME/CFS symptoms.
@Kalliope posted a link to a pertinent argument raised by Dr Yngve Thomas Bliksrud in the Journal of the Norwegian Medical Association (Google translation here), in which Dr Bliksrud discusses Fluge and Mella's results, and points out that:
Dr Bliksrud says the fact that patients with genetic PDH deficiency diseases do not generally experience fatigue suggests that the PDH impairment found by Fluge and Mella may not be the cause of ME/CFS.
But conceivably Fluge and Mella's PDH impairment may be a consequence of some other more fundamental energy metabolism dysfunction in ME/CFS, rather than the actual cause of the ME/CFS energy dysfunction.
So what might be the real underlying energy metabolism dysfunction that both causes ME/CFS, and gives rise to this PDH impairment?
One possibility is comes from the 2009 energy metabolism studies of Myhill, Booth and McLaren-Howard where they found that the mitochondrial translocator protein is blocked in ME/CFS, and posited this causes an energy metabolism blockage. (Note though that translocator protein blockage was not the only energy metabolism impairment found by Myhill et al in ME/CFS).
Myhill, Booth and McLaren-Howard point out that if the translocator protein is blocked, then pyruvate dehydrogenase automatically becomes inhibited. See their 2012 study:
So it's possible that the PDH inhibition found by Fluge and Mella may be a consequence of the translocator protein blockage found by Myhill, Booth and McLaren-Howard in ME/CFS patients. Or may be a consequence of some other as yet undiscovered energy metabolism dysfunction.
Note that Myhill et al use the term "translocator protein" to refer to the adenine nucleotide translocator (ANT).
Also of relevance: Enterovirus-Induced ANT Autoantibodies: the Cause of ME/CFS? Could autoantibodies that target ANT (the mitochondria translocator protein) be the cause of ME/CFS? Such ANT autoantibodies would certain fit in with Fluge and Mella's finding that there is "something in the serum" of ME/CFS patients that is causing the energy metabolism blockage (autoantibodies are found in the blood serum).
A new argument suggests pyruvate dehydrogenase (PDH) impairment may not be a candidate for the underlying cause of ME/CFS.
In Fluge and Mella's 2016 metabolomic study, they found impaired pyruvate dehydrogenase function in ME/CFS, and it has been speculated this might be the cause of the apparent energy metabolism dysfunction of this disease — a dysfunction which causes fatigue and other ME/CFS symptoms.
@Kalliope posted a link to a pertinent argument raised by Dr Yngve Thomas Bliksrud in the Journal of the Norwegian Medical Association (Google translation here), in which Dr Bliksrud discusses Fluge and Mella's results, and points out that:
Chronic fatigue is not a typical symptom in patients with primary genetic pyruvate dehydrogenase deficiency, neither severe nor mild
Dr Bliksrud says the fact that patients with genetic PDH deficiency diseases do not generally experience fatigue suggests that the PDH impairment found by Fluge and Mella may not be the cause of ME/CFS.
But conceivably Fluge and Mella's PDH impairment may be a consequence of some other more fundamental energy metabolism dysfunction in ME/CFS, rather than the actual cause of the ME/CFS energy dysfunction.
So what might be the real underlying energy metabolism dysfunction that both causes ME/CFS, and gives rise to this PDH impairment?
One possibility is comes from the 2009 energy metabolism studies of Myhill, Booth and McLaren-Howard where they found that the mitochondrial translocator protein is blocked in ME/CFS, and posited this causes an energy metabolism blockage. (Note though that translocator protein blockage was not the only energy metabolism impairment found by Myhill et al in ME/CFS).
Myhill, Booth and McLaren-Howard point out that if the translocator protein is blocked, then pyruvate dehydrogenase automatically becomes inhibited. See their 2012 study:
If TL [translocator protein] is not working properly, oxidative phosphorylation will be inhibited, pyruvate dehydrogenase becomes inhibited and also the Krebs cycle
So it's possible that the PDH inhibition found by Fluge and Mella may be a consequence of the translocator protein blockage found by Myhill, Booth and McLaren-Howard in ME/CFS patients. Or may be a consequence of some other as yet undiscovered energy metabolism dysfunction.
Note that Myhill et al use the term "translocator protein" to refer to the adenine nucleotide translocator (ANT).
Also of relevance: Enterovirus-Induced ANT Autoantibodies: the Cause of ME/CFS? Could autoantibodies that target ANT (the mitochondria translocator protein) be the cause of ME/CFS? Such ANT autoantibodies would certain fit in with Fluge and Mella's finding that there is "something in the serum" of ME/CFS patients that is causing the energy metabolism blockage (autoantibodies are found in the blood serum).
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