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Ron Davis study showed abnormal impedance , when pyruvate was added they cells behave normally . the Stanford study showed higher than normal atp production through nonmitochondrial pathway (probably glycolysis). I think 2,3 dpg is the difference.
Ron Davis study used mononuclear cells in patients serum . Cfs patient serum contain higher level of 2,3dpg . the 2,3dpg is taken up by mononuclear cells . 2,3dpg inhibits hk, pfk and gapd . This results in lower levels of glycolytic intermediates and lower pyruvate production. When they added pyruvate the cells behaved normally because the added pyruvate provided substrate for oxidative phosphorylation .
The standford study used patient mononuclear cells but not in patient serum . the serum contains the higher than normal 2,3dpg levels. the patient mononuclear cells were adapted to inhibition by 2,3dpg ( they tried increase their activity to adjust to the inhibition by 2,3dpg. When they took these cells out of the serum to do the studies , the 2,3dpg were no longer there , so the inhibition of glycolytic enzymes by 2,3dpg were no longer there as a result the glycolytic activity in these mononuclear cells became overly activated and resulted in higher atp production from higher than normal glycolysis.
My guess as to the cause of cfs is higher levels of oxidative stress , upregulation of the antioxidant system , lowering of oxidative phosphorylation, and higher dependence on aerobic glycolysis for atp production . there is a change in genes and expression of enzyme involved in glycolysis and the antioxidant system . This change is happeneing in muscle and brain. PKM2 is upregulated (usually PKM1 is the dominant isoform ), p53 is downregulated (p53 is important for oxidative phosphorylation cytochrome c oxidase) , nrf2 may also be upregulated , its involved in the antioxidant system , glutamine metabolism , glutamine metabolism has been shown to be high in cfs. total glutathione may also be high in muscle be high in brain and muscle but maybe low in other places . the upregulation of PKM2 lowers p53 activity. Lower p53 activity results lower oxidative phosphorylation, we become more dependent on aerobic glycolysis for energy production , this is why we see higher lactae levels during activity . the activity of PKM2 is lower than PKM1 . The lower activity of PKM2 results in a build up of glycolytic intermediates . One of these is 2,3dpg. (but normalizing 23dpg levels isn't gona fix cfs).
In order to fix cfs, we need to normalize the aerobic glycolysis and oxidative phosphorylation . We need to upregulate p53 to increase oxidative phosphorylation ( I have been looking at some compounds, molecules that might can do this ). I've had cfs for 20 years , its been a gradual decline
Ron Davis study used mononuclear cells in patients serum . Cfs patient serum contain higher level of 2,3dpg . the 2,3dpg is taken up by mononuclear cells . 2,3dpg inhibits hk, pfk and gapd . This results in lower levels of glycolytic intermediates and lower pyruvate production. When they added pyruvate the cells behaved normally because the added pyruvate provided substrate for oxidative phosphorylation .
The standford study used patient mononuclear cells but not in patient serum . the serum contains the higher than normal 2,3dpg levels. the patient mononuclear cells were adapted to inhibition by 2,3dpg ( they tried increase their activity to adjust to the inhibition by 2,3dpg. When they took these cells out of the serum to do the studies , the 2,3dpg were no longer there , so the inhibition of glycolytic enzymes by 2,3dpg were no longer there as a result the glycolytic activity in these mononuclear cells became overly activated and resulted in higher atp production from higher than normal glycolysis.
My guess as to the cause of cfs is higher levels of oxidative stress , upregulation of the antioxidant system , lowering of oxidative phosphorylation, and higher dependence on aerobic glycolysis for atp production . there is a change in genes and expression of enzyme involved in glycolysis and the antioxidant system . This change is happeneing in muscle and brain. PKM2 is upregulated (usually PKM1 is the dominant isoform ), p53 is downregulated (p53 is important for oxidative phosphorylation cytochrome c oxidase) , nrf2 may also be upregulated , its involved in the antioxidant system , glutamine metabolism , glutamine metabolism has been shown to be high in cfs. total glutathione may also be high in muscle be high in brain and muscle but maybe low in other places . the upregulation of PKM2 lowers p53 activity. Lower p53 activity results lower oxidative phosphorylation, we become more dependent on aerobic glycolysis for energy production , this is why we see higher lactae levels during activity . the activity of PKM2 is lower than PKM1 . The lower activity of PKM2 results in a build up of glycolytic intermediates . One of these is 2,3dpg. (but normalizing 23dpg levels isn't gona fix cfs).
In order to fix cfs, we need to normalize the aerobic glycolysis and oxidative phosphorylation . We need to upregulate p53 to increase oxidative phosphorylation ( I have been looking at some compounds, molecules that might can do this ). I've had cfs for 20 years , its been a gradual decline