pattismith
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@nandixon
In some ME/CFS studies, alterations in the purine metabolism were found.
Low adenosine in the Naviaux (and high eATP)
Low IMP and cAMP in the Hanson
These changes are very close to what was found in Zinc deficiency, and many symptoms in ME/CFS patients overlap with Zinc deficiency .
"Zinc deficiency causes delayed ATP clearance and adenosine generation in rats and cell culture models
Abstract
Zinc deficiency causes myriad pathophysiological symptoms, but why distinct phenotypes are generated by zinc deficiency remains unclear.
Considering that several ectoenzymes involved in purinergic signaling through extracellular adenine-nucleotide hydrolysis possess zinc ions in their active sites, and disorders in purinergic signaling result in diverse diseases that are frequently similar to those caused by zinc deficiency, herein we examine whether zinc deficiency affects extracellular adenine-nucleotide metabolism. Zinc deficiency severely impairs the activities of major ectoenzymes (ENPP1, ENPP3, NT5E/CD73, and TNAP), and also strongly suppresses adenine-nucleotide hydrolysis in cell-membrane preparations or rat plasma, thereby increasing ATP and ADP levels and decreasing adenosine levels.
Thus, zinc deficiency delays both extracellular ATP clearance and adenosine generation, and zinc modulates extracellular adenine-nucleotide metabolism.
Since the finely tuned balance between extracellular adenine nucleotides and adenosine is critical for purinergic signaling, these findings provide a novel insight into why zinc deficiency results in diverse symptoms."
Note:
They didn't study intracellular purine metabolism, but ADA and AMPA are two important zinc-dependent enzymes in purine metabolism that produce Inosine and IMP by deamination, so low Inosine and IMP would be relevant in Zinc deficiency as well.
Note bis:
Interestingly Zinc is also a P2X7 receptor antagonist (whereas eATP is activator),
here a recent study about this potency:
"Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia.
Kovacs 2018
Abstract
The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective cation channel, is expressed in different cell types of the central nervous system in several regions of the brain. The activation of the P2X7R protein by ATP modulates excitatory neurotransmission and contributes to microglial activation, apoptosis and neuron-glia communication. Zinc is an essential micronutrient that is highly concentrated in the synaptic vesicles of glutamatergic hippocampal neurons where free zinc ions released into the synaptic cleft alter glutamatergic signal transmission. Changes in both P2X7R-mediated signaling and brain zinc homeostasis have been implicated in the pathogenesis of mood disorders. Here, we tested the hypothesis that extracellular zinc regulates P2X7R activity in the hippocampus.
We observed that P2X7R is expressed in both neurons and glial cells in primary mouse hippocampal neuron-glia culture.
Propidium iodide (PI) uptake through large pores formed by pannexins and P2X7R was dose-dependently inhibited by extracellular zinc ions.
Calcium influx mediated by P2X7R in glial cells was also reduced by free zinc ions.
Interestingly, no calcium influx was detected in response to ATP or 3'-O-(4-Benzoyl) benzoyl ATP (BzATP) in neurons despite the expression of P2X7R at the plasma membrane.
Our results show that free zinc ions can modulate hippocampal glial purinergic signaling, and changes in the activity of P2X7R may contribute to the development of depression-like behaviors associated with zinc deficiency."
In some other studies, zinc deficiency was found to decrease Deiodinase type I activity. (convert T4 to T3 in Liver, Kidney and muscle). Deiodinase type I hypoactivity is involved in Low T3 syndrome, which was found in a subset of ME/CFS patients in the Nederland study.
In some ME/CFS studies, alterations in the purine metabolism were found.
Low adenosine in the Naviaux (and high eATP)
Low IMP and cAMP in the Hanson
These changes are very close to what was found in Zinc deficiency, and many symptoms in ME/CFS patients overlap with Zinc deficiency .
"Zinc deficiency causes delayed ATP clearance and adenosine generation in rats and cell culture models
- (2018)
Abstract
Zinc deficiency causes myriad pathophysiological symptoms, but why distinct phenotypes are generated by zinc deficiency remains unclear.
Considering that several ectoenzymes involved in purinergic signaling through extracellular adenine-nucleotide hydrolysis possess zinc ions in their active sites, and disorders in purinergic signaling result in diverse diseases that are frequently similar to those caused by zinc deficiency, herein we examine whether zinc deficiency affects extracellular adenine-nucleotide metabolism. Zinc deficiency severely impairs the activities of major ectoenzymes (ENPP1, ENPP3, NT5E/CD73, and TNAP), and also strongly suppresses adenine-nucleotide hydrolysis in cell-membrane preparations or rat plasma, thereby increasing ATP and ADP levels and decreasing adenosine levels.
Thus, zinc deficiency delays both extracellular ATP clearance and adenosine generation, and zinc modulates extracellular adenine-nucleotide metabolism.
Since the finely tuned balance between extracellular adenine nucleotides and adenosine is critical for purinergic signaling, these findings provide a novel insight into why zinc deficiency results in diverse symptoms."
Note:
They didn't study intracellular purine metabolism, but ADA and AMPA are two important zinc-dependent enzymes in purine metabolism that produce Inosine and IMP by deamination, so low Inosine and IMP would be relevant in Zinc deficiency as well.
Note bis:
Interestingly Zinc is also a P2X7 receptor antagonist (whereas eATP is activator),
here a recent study about this potency:
"Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia.
Kovacs 2018
Abstract
The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective cation channel, is expressed in different cell types of the central nervous system in several regions of the brain. The activation of the P2X7R protein by ATP modulates excitatory neurotransmission and contributes to microglial activation, apoptosis and neuron-glia communication. Zinc is an essential micronutrient that is highly concentrated in the synaptic vesicles of glutamatergic hippocampal neurons where free zinc ions released into the synaptic cleft alter glutamatergic signal transmission. Changes in both P2X7R-mediated signaling and brain zinc homeostasis have been implicated in the pathogenesis of mood disorders. Here, we tested the hypothesis that extracellular zinc regulates P2X7R activity in the hippocampus.
We observed that P2X7R is expressed in both neurons and glial cells in primary mouse hippocampal neuron-glia culture.
Propidium iodide (PI) uptake through large pores formed by pannexins and P2X7R was dose-dependently inhibited by extracellular zinc ions.
Calcium influx mediated by P2X7R in glial cells was also reduced by free zinc ions.
Interestingly, no calcium influx was detected in response to ATP or 3'-O-(4-Benzoyl) benzoyl ATP (BzATP) in neurons despite the expression of P2X7R at the plasma membrane.
Our results show that free zinc ions can modulate hippocampal glial purinergic signaling, and changes in the activity of P2X7R may contribute to the development of depression-like behaviors associated with zinc deficiency."
In some other studies, zinc deficiency was found to decrease Deiodinase type I activity. (convert T4 to T3 in Liver, Kidney and muscle). Deiodinase type I hypoactivity is involved in Low T3 syndrome, which was found in a subset of ME/CFS patients in the Nederland study.