Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
I thought Bb was inhibiting a phosphate transfer to the amino acid, serine. I was WRONG.
It appears Bb inhibits a phosphate transfer to the amino acid, tyrosine, which impacts our ATP synthase.
ATP synthase helps us to MAKE ATP. Keep in mind...we're talking about the cells Bb is INFECTING. These cells are making far too little ATP and they are our defensive cells!
The following is very complex.
Bb has a "PKC inhibitor" Protein Kinase C inhibitor. Kinases transfer phosphates. C stand for CALCIUM.
Then there are subsets of PKC...delta is one. That is the one I think Bb is inhibiting (PKCd).
PKCd inhibition is linked to the following: Y52-p, Y64-p, Y187-p which look to be where tyrosine is supposed to be linked to phosphate.
Now the really tough stuff:
"platelet-derived growth factor (PDGF), which is linked in signal transduction pathways to tyrosine kinase-dependent phosphorylations, regulates the phosphorylation of the
***mitochondrial ATP synthase delta subunit*** in cortical neurons (Zhang et. al., 1995. J. Neurochem. 65, 2812-2815).
This is a particularly intriguing finding in light of more recent reports demonstrating that ATP synthases are nanomotors with a central rotor, one component of which is the delta subunit.
In this report, evidence is provided that the PDGF-dependent phosphorylation of the ATP synthase delta subunit is not confined to neuronal cells but can be demonstrated also in studies with PDGF-treated NIH3T3 and ***kidney cells***.
Evidence is provided also that phosphorylation of the ATP synthase delta subunit may involve its single tyrosine residue, and that this phosphorylation is modulated when the cell based assay includes lysophosphatidic acid (LPA), a phospholipid signaling molecules.
Finally, results are presented of an analysis which revealed a number of
potential tyrosine phosphorylation sites on
three other subunits (alpha, beta, and gamma) of the F1 (catalytic) moiety of the mitochondrial ATP synthase,
thus making this important complex a most attractive target for future signal transduction studies. PMID: 16120288
Basically, Bb is scr...messing up...our ATP synthase which is needed to help us MAKE ATP.
How can we INCREASE ATP in the infected cells?
Far infrared therapy.
Photon (energy transfer). I linked you all to an animated video.
When photons enter the cells, they trigger a G protein (helper protein) called transducin, which closes the "gates" and keeps Na and Ca (CALCIUM) IN THE CELLS. This INCREASES the amt. of calcium in the cytoplasm of the cells...
Those of you who have been here for awhile will appreciate this:
"Our results suggest that the initial rise in cytoplasmic calcium seen
on application of ***2,4-dinitrophenol*** (DNP)
results from *release of mitochondrial calcium* because of mitochondrial depolarization."
Trying to increase cytoplasmic Ca levels by getting it from the mitochondrial stores.
It appears far infrared also helps to increase cytoplasmic Ca levels by "closing the doors" (as seen on the animated video)which prevents Ca (and Na) from "exiting" the "stage"...so to speak.
DNP is in the class with cyanide! It was used as a "weight loss" chemical and was used to cause intracellular hyperthermia (ICHT)illegally in Italy. The use of this chemical caused the death of a doctor who had lyme disease. It likely disrupted his electrolyte balance and caused a cardiac arrest.
There appears to be a HUGE difference between raising Ca levels in the cytoplasm of the cell via far infrared and "draining" Ca from the mitochondria to raise the level of the cytoplasmic Ca levels.
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seekhelp
Frequent Contributor (5K+ posts)
Member # 15067
posted
Wow...I'll get back in a year after I read this 450 times. Where do you dig up these facts? Have you thought about compiling all your research and working with a facility/individual who truly can comprehend it and perhaps formulate treatment plans?
Very interesting though about ATP. I was undergoing physican therapy at a facility that used frequency specific microcurrent and I was feeling somewhat better when used consistently.
Guess what it did? It increased ATP production by 500%. Coincidence?
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Pinelady
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-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Bb has a gene for Na-ATPase. It uses NaCl for motility. It has a gene for transferrin (*transports* iron, while lactoferrin binds iron)....
On and on...
This is one incredibly complex pathogen!
Yes, we do indeed need to increase ATP levels in the infected cells!
ATP will drive Mg back in where Mg-ATP helps to transfer phosphate groups.
I now have about 4000 MS word files...YIKES!
and...
Ancora Imparo!
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lymeHerx001
Frequent Contributor (1K+ posts)
Member # 6215
posted
Marnie only speaks in code. lol
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seekhelp
Frequent Contributor (5K+ posts)
Member # 15067
posted
Hey I understood the last message from Marnie. Posts: 7545 | From The 5th Dimension - The Twilight Zone | Registered: Mar 2008
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posted
Marnie, I missed the link between PKC inhibition and production of ATP synthase. How is it that PKC inhibition leads to decreased levels of ATP synthase?
Presumably the PKC inhibition is happening in the cellular cytoplasm, since the Bb would not physically fit inside the mitochondria where the ATP synthase is embedded in the inner membrane.
Wouldn't a decrease in ADP phosphorylation due to the disruption of ATP synthase in the electron transport chain manifest with the same symptoms typical of DNP ingestion - body temp increase, intracellular fluid retention and rapid fat loss due to increased gluconeogenesis?
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disturbedme
Frequent Contributor (1K+ posts)
Member # 12346
posted
LOL. Code for sure. I didn't understand any of it. Though I'm also sitting here unable to keep my eyes open. Time to take a nap.
-------------------- One can never consent to creep when one feels an impulse to soar. ~ Helen Keller
My Lyme Story Posts: 2965 | From Land of Confusion (bitten in KS, moved to PA, now living in MD) | Registered: Jun 2007
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posted
Sorry, I am so not getting this. So we take more Iron?
-------------------- Amy
Diagnosed April 29, 2007. Posts: 136 | From Joplin, MO | Registered: Apr 2007
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
If Bb is inhibiting a phosphate transfer to tyrosine (inhibits PKCd), this may impact our ATP synthase(which helps us to make ATP).
PKC... P = protein K= kinase (kinases transfer phosphates) C stands for calcium.
"In addition, PKCδ (delta symbol) maintains homeostasis by phosphorylating the calcium efflux regulator PMCA (plasma membrane calcium ATPase) regulating Ca2+ levels in the skin."
If Bb is INHIBITING this form of PKC (delta)...the calcium efflux regulator - plasma membrane *calcium ATPase*...isn't working because a phosphate transfer doesn't happen.
Then does the body, in response, upregulate the TRPM8 channel which helps to push Ca out?
"Both T. pallidum and B. burgdorferi, similarly to Mycoplasma genitalium, are limited in their biosynthetic capabilities.
B. burgdorferi in culture requires large concentrations of N-acetylglucosamine, which forms the chitin polymer. Fructose 6-phosphate and N-acetylglucosamine are interconvertible in the pathway of glycolysis.
The proton-generating ATP synthase is present and needed to pump protons across the membrane."
"In parallel to this, strong downregulation of *serpin F1*, an anti-plasmin, might result in higher plasmin levels, which in turn accelerates fibrinolysis.
F1 all gone?
We know Bb locks onto plasminogen -> plasmin which triggers the metalloproteinases.
Okay...let's get more complex (Ugh!)
"We have recently reported the identification of kringle 1-5 (K1-5) of plasminogen as a potent and specific inhibitor of angiogenesis and tumor growth.
Here, we show that K1-5
bound to endothelial cell surface ATP synthase
and triggered caspase-mediated endothelial cell apoptosis."
But PKCd if INactivated, looks to prolong the life of the cell.
My mind is swirling...how's yours?
Amy...Bb has a gene to *transport iron*. It is called transferrin. Bb doesn't particularly like a lot of iron...it is toxic to Bb.
Persons who have iron-overload problems = hemochromatosis (and need "blood-letting" every few months) do not look to be "protected" from lyme disease.
Others...Bb looks like it maybe robbing us of a portion of OUR ATP synthase (helps us to make ATP) in the cells it infects.
TCW...body temp. drops to conserve oxygen (we need less oxygen if we get really cold...like falling thru the ice and still be able to survive)...edema happens in lyme...esp. legs...many lyme patients develop hypothyroid = weight GAIN. Protective from some respects.
The HPA axis is thrown off as well as the HPT axis. This pathogen really messes with our neurotransmitters and hormones, etc.
I think you are right about Bb's cytoplasm location.
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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Sweetie, every since I got sick my brain has a syllable limit. No more than one or two. I used to love big words.
So, we should make sure Iron levels are ok or no?
-------------------- Amy
Diagnosed April 29, 2007. Posts: 136 | From Joplin, MO | Registered: Apr 2007
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Yes. Watch your iron levels.
If your PFK levels drop (and they do) this can and does trigger anemia.
Bb is PFK dependent. That enzyme is needed for glycolysis.
The body will try to halt this via triggering IL 1 B because insulin activates PFK1 and PFK2.
Good and bad...IL 1B. Same with TNF alpha. One thing is for sure...TOO MUCH of these is very very harmful.
They are defense measures, but it is like dropping a bomb instead of a gun-shot direct hit.
Our astronauts (in absolute darkness and in zero gravity) return to earth with low PFK levels and are anemic.
We have learned a LOT from trying to figure out how to protect our astronauts.
This includes far infrared research!
In cases of serious infections, the body often goes into an "iron storage" mode since MANY pathogens (not Bb, but others) need iron to replicate.
Keep an eye on the spleen.
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Pinelady
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posted
She is saying yes, but it is a catch 22. We need they need thingy. So what gives Bb its most help at survival? Marnie do you think it is glucose?
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
"So what gives Bb its most help at survival? "
Looks to be Na primarily.
But we need to close the chloride channel, TRPM8 which involves Na AND Ca.
It appears Bb likes it if Ca LEAVES.
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Pinelady
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posted
This sounds hormonal truly.
Could it be it is hormonal?
Feeding on the Na and giving off the Cl-,
using up all the D, getting rid of the Ca?
If it does not require the protein I see no option
but to kill it with its own kind if that was the
case. And I know that has been tried. So?
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
We know Bb coats itself in the Salp 15 protein (from the tick's saliva) and this protein interfers with Ca fluxes and this allows Bb to gain an *initial foothold*.
Then it locks onto our plasminogen which -> plasmin -> triggers our metalloproteinases to "pave the way".
To cure SARS...researchers GAVE MORE of what that virus locked onto and the virus locked onto the EXCESS and did not infect the person.
Plasminogen as a first line of defense?
Aldosterone is upregulated to try to control Na levels. Vitamin B6 does that too. Bb can NOT make B6.
See the aldosterone, testosterone and estrogen implications?
The steroid hormones come from...the precursor is cholesterol and Bb takes the cholesterol pathway to build its cell walls.
We are trying to counter Bb's PKC inhibitor which is, IMO, the worse thing about this spirochete. Bb is preventing phosphate transfers onto amino acids.
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Pinelady
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posted
LOL What if you have a parathyroid adenoma?
Secreting the hormone that overproduces blood Ca.
While at the same time appearing to be normal blood Ca?
Could this hormone be used to block the synthesis?
Just thinking out loud.
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
I did it again.
Bb's endotoxin looks to cleave (break apart) MAPKK-1.
This leads to the dephosphylorization of 2 serines.
2 phosphates look to be *removed* from serine.
Next question: doesn't that mess up the HPA axis since phosphatidylserine is what helps to keep it in balance?
At death, NO ATP at ALL is made (obviously) and serine is rapidly dephosphorylated (phospho-Ser-GSK3 is dephosphorylated).
If those serines WERE phosphorylated (2 phosphates added back on) then GSK3 would be inhibited.
GSK3 (Glycogen synthase kinase-3) is inhibited by phosphorylation of serine-9 or serine-21 in GSK3β and GSK3α, respectively.
"Inactivation of glycogen synthase kinase 3b stimulates myogen differentiation similar to insulin like growth factor-I"
"Glycogen Synthase Kinase-3β (GSK-3β) is a multifunctional serine/ threonine kinase that inhibits glycogen synthesis"..(couldn't bring up the abstract)
"Glycogen synthase kinase-3β is involved in the phosphorylation and suppression of androgen receptor activity...
If glycogen synthase kinase 3B is inhibited, then the androgen receptor driven transcription could occur.
"Voltage-gated ***sodium channel blockers*** as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3"
Conversely, the glycogen synthase kinase-3β inhibitor lithium chloride suppressed the glycogen synthase kinase-3β-mediated phosphorylation of the androgen receptor, thereby enabling androgen receptor-driven transcription to occur."
"The mechanism by which lithium (Li(+)) inhibits the protein kinase glycogen synthase kinase-3 (GSK-3) is unknown.
Here, we demonstrate that Li(+) is a competitive inhibitor of GSK-3 with respect to magnesium (Mg(2+)), but not to substrate or ATP.
This mode of inhibition is conserved between mammalian and Dictyostelium GSK-3 isoforms, and is not experienced with other group I metal ions.
As a consequence, the potency of Li(+) inhibition is dependent on Mg(2+) concentration.
We also found that GSK-3 is sensitive to chelation of free Mg(2+) by ATP and is progressively inhibited when ATP concentrations exceed that of Mg(2+).
Given the cellular concentrations of ATP and Mg(2+), our results indicate that Li(+) will have a greater effect on GSK-3 activity in vivo than expected from in vitro studies and this may be a factor relevant to its use in the treatment of depression."PMID: 11162580
"Insulin is capable of increasing intracellular magnesium".
Insulin ACTIVATES PFK (1 and 2) and Bb is "PFK dependent".
"Glucose and insulin showed opposite effects in their ability to modify Mgi2+ in lymphocytes.
Inhibitors of the membrane Na+- Mg2+ transport system and of phosphatidylinositol (PI) 3-kinase abolish the insulin-mediated increase of Mgi2+,
thus suggesting that insulin is capable of increasing Mgi2+ by modulating the activity of this transport system, possibly through the mediation of PI 3-kinase activation.
But the infected cells become "insulin resistant".
"Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes."
Is Il1B keeping the infected cells "immortal" and functioning only via glycolysis - using glucose to make ATP and not allowing the influx of Mg into lymphocytes?
Does it not look like it is very important that phosphates be added to the 2 serines to inhibit GSK3?
"Phosphorylation (inhibition) of glycogen synthase kinase-3β (GSK3β) has been involved in cardioprotection.
These results suggest that S9-phosphorylation of GSK3β(beta) is required for postconditioning and likely acts by inhibiting the opening of the mitochondrial permeability transition pore."
About GSK3a (alpha):
"Here, we show that serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta are also physiological substrates of cAMP-dependent protein kinase A. Protein kinase A physically associates with, phosphorylates, and inactivates both isoforms of GSK-3."
And apparently...
"Release of ADP from the catalytic subunit of protein kinase A"
Can we "re-energize" those infected cells - stimulate the phosphate transfers? Are there any funcional mitochondria remaining?
I'm trying so hard to understand this myself and to try to "translate" it to those of you who are interested in the "whys".
[ 04-28-2009, 11:57 AM: Message edited by: Marnie ]
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Where do you dig up these facts? Have you thought about compiling all your research and working with a facility/individual who truly can comprehend it and perhaps formulate treatment plans? 
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I used to love big words.
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