EPO plus APS : mitochondrial revolution
Andre Willers
26 Sep 2013
Synopsis :
Combining EPO and APS synergistically gives at least twice
the efficiency to mitochondria .
Discussion :
1.EPO
Latest discoveries is that a high pulse of EPO activates
switches on the cell-wall and mitochondria , making the process up to 50% more
effective if it comes under stress .
See the journals .
2.APS
See Appendix 1 on how it works .
Mitochondrial spin can be influenced in any organ , even the
heart.
About 1/3 (personal experience)
3.Resultant effectiveness :
Effectiveness = 1.333x1.5
= 1.999
4.Sports :
Aerobic stress sports endurance can be doubled . Marathons ,
tennis , etc
5.Heart :
Heart attack patients with damaged heart muscles can have at
least double the chance of survival .
Do it or not .
Your choice .
Andre
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Appendix 1.
ATP as Neurotransmitter
Andre
Willers
18 Jan 2010
Synopsis :
ATP has been
proven to be a neurotransmitter . Various receptor sites on cellwalls have been
found as result of the Human Genome project . Important health considerations
result .
Discussion :
See
important article in ScientificAmerican Dec 2009 , p60 "The double life of
ATP" by BS Khakh and G Burnstock (let us hope that nominative determinism
does not hold sway .)
Beg , borrow
, steal or buy a copy .
See http://andreswhy.blogspot.com "ATP
and Catalytic Motors" . Appended in Appendix A for ease of reference .
Crackpot
duckling into Swan :
The effect
had been clinically demonstrated since 1959 , but disregarded as not fitting
into the accepted model .
The
isolation of certain ATP and ADP receptors in 1993 and 1994 , as well as
development of Clopidogrel to prevent clot formation led to greater acceptance
.
The Human
Genome Project led to the genes for receptor sites of ATP and it's various
breakdown products . It is now a Hot Subject (ie fashionable) . A number of
drugs are in various development stages .
A lot of
money , major health items and knowledge is in play .
A Brief
Description .
It is a very
elegant mechanism . Also very old .
1. ATP =
Adenosine + P + P + P
=
AdenosineTriPhosphate
2. ABP=
AdenosineBiPhosphate (the last phosphor atom has been stripped away . This is
energy bond powering the muscles)
3. AMP=
AdenosineMonoPhosphate . Only one phosphor atom .
4. Adenosine
is adenosine (a purine) without any phosphor atoms .
Every cell
has specialized receptor sites on the surface that interacts with one or a
combination of these compounds . This gives at least 2^4=16 possible basic
receptor types .
The
information being triggered is in the cell-wall (the Phene system) . This
causes various portals to open or close , influencing sodium , calcium , etc
balances in cellular substructures (including DNA in the chain)
Surrounding
the cells are class of enzymes called EctoATPases that sequentially strip away
the phosphor atoms from ATP .
This
stripping of phosphor atoms makes the whole system workable by creating four
unique markers necessary and sufficient for a three dimensional contiguous
information space.
A teensy
little problem is : where does all this energy go ? Heating up the synaptial
fluid seems to be a result . Is this essential for multi-cellular life ? The
intercellular information transfer spaces are then always hot and ready to roll
. Certainly , it would give a great advantage to even a cold-blooded lifeform .
The energy costs would not be very high .
From an
evolutionary viewpoint , it is easy to see that a temperature control mechanism
in synaptial fluids expanded into the whole organism in a random
mutational-selection process .
But what is
the original mechanism ?
See ApendixA
"Throttle"
It must
involve the production speed of ATP : ie the rotational speed of the rotor in
the mitochodria .
There are
two known ways to influence this:
1.Melatonin
Ironically ,
sleep seems to be basically necessary to give synaptical spaces a chance to
cool down . If they grow too hot , the other neurotransmitters start breaking
down and the well-known dementia of sleeplessness results . Obviously , the immune
system is affected as well . This whole ATP signaling system is part of the
immune control-system .
Note the
correlation of symptoms between heat-stroke , sleeplessness and forms of
dementia associated with various neurotransmitter shortages .
2.APS
generator .
(See
AppendixA)
The pulsed
waveform will not only speed up lagging mitochondrial rotors, but also slow
down ones that are too fast (ie overproducing ATP) . This should ameliorate
synaptial fluid overheating .
Ideally , we
should have an APS generator that can force a desired spin rate on any set of
organs . But the one we can buy now is set at 3 milliseconds .
Remember , a
standard human produces about 40 Kg of ATP per day (See AppendixA)
An useful
analogue:
Using the energy
transmission conduit also as an information transmission route is used in
electrical systems . You can buy a system that uses the electrical wiring of
your home to transmit music , video , internet , etc .
The analogue
goes both ways , since the problems with the electrical system will also be
experienced in the ATP system .
Known
systems using ATP as neurotransmitter:
1.Blood
vessel constriction : ATP as co-neurotransmitter with noradrenaline .
2. Blood
vessel dilation : shear stress->ATP->NO->vessel relaxation.Part of the
feedback system .
3.Blood
clotting: platelets have ADP receptors.
4.Cell
proliferation : eg restinosis , various cancers . See Phene control system .
5.Eye:
acetylcholine and ATP are co-neurotransmitters.
6.Ear :about
50% of cochleal hairs have ATP receptors.
7.Taste:as
expected , evolutionary old chemical receptors like taste or smell do not
function without ATP receptors(in this case P2X2 and P2X3 receptors) .
8.Pain and
touch: mainly the P2X3 receptor .
9.Neuropathy
:
P2X
receptors are involved .
10.Digestive
system:
Irritable
bowel syndrome and Crohn's disease :P2X and P2Y receptors are involved .
11.Clotting
:
Existing drugs
Clopidogrel and Prasugrel blocks P2X12 receptor .
12.Tumors ,
developmental diseases , etc .
13.Disease
regulation using bacterial ATP signaling.
14.Old Age
Apoptosis
and ATP quorum mechanisms await exploration .
The Phene
System:
It seems
that the ATP signaling systems plays an important part in the meta-control
system of multi-cellular organisms (multi-cellular includes a single cell with
a mitochondrium by definition) .
We know that
viruses encapsulated by cell-wall material is the signaling mechanism of cells
.
Speculation
: Distributed Viruses .
That ATP ,
ADP , AMP and Adenosine plus receptor sites form a distributed virus
The crystal
structure of the P2X receptor looks like a typical virus . It only needs the
key(s) to activate . As expected from a phene control mechanism , it regulates
activities in the cell via switching on or off of genes in the DNA .
(See how
handy the concept of phenes is ?)
Even more
speculative :
Do not try
this without qualified supervision .
Diseases
like AIDS , cancer or old age must interact with the ATP signaling system at
some stage . Quorum systems play a role (why we use melatonin)
Slow down
the mitochondrial rotors with melatonin , and simultaneously entrain them with
a APS generator on selected organs . Pulse if necessary .
This will
hopefully break interlocked feedback cycles .
Interestingly
, this should work on fevers as well , as well as disrupt quite a few viral
diseases .
A hot time
in the old town tonight .
Andre .
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Appendix A
ATP and Catalytic Motors
Andre
Willers
4 Dec 2008
The
Catalytic Motor.
See Annexure
A below .
This is a
new concept to me .
The basic
principle :
The chemical
equilibrium of a reaction is biased in a certain direction by dynamical ,
rotational processes .
And not in a
trivial way either . A whopping 40 kg per day production and consumption of ATP
for a sedentary human (of say mass 80 kg) means a very finely balanced
mechanism . (Half of body mass per day)
The logistical
demands almost necessitate a multi-cellular organism .
Where does
the rotor come from ?
From
bacterial flagellae . They work by rotation of the flagella .(Google it)
The rotor is
driven by proton gradients , caused by electron-flow balances between inflowing
nutrients and usage .
Putative
evolution :
The
ur-mitochondrium was a free organism whose flagellae by chance could beat two
poisons (oxygen and alcohol) into harmless ATP . As if protein-folding was not
complicated enough , now dynamics have to be considered as well .
As the
concentrations of these poisons increased , ur-mitochondria did the usual
plaque - freeform alternation of bacteria . In every colony episode , the
efficiency of the conversion was enhanced . At some stage , a freeform colonized
some other bacterium . The host learned to use ATP as an energy source .
Multicellular forms were force-formed .
The motors
of the mitochondria cannot stop spinning . (If they do , apoptosis results: see
Appendix B) . The ATP has to be used .
Rotor-spin
speed:
This seems
to be quite slow . (As expected from a flagella heritage) . About one to three
milliseconds per revolution . ( About 1 to 0.3 kHz) . The ATP production is not
smooth either . There are three units physically opening and closing (see
Appendix A).
A very
useful analogue:
We can use
an national electricity grid operating at 1 kHz alternating current of
three-phase current as an tool for understanding the meta-energy flow in the
body . Every cell would be like a municipality with its own powerstation .
The voltage
and transformers ? Nobody has looked , but a guess would be ATP concentration
regulators , like the reticular cellular formations , antioxidants (see
Appendix B) , ATP chaperones , cellular-wall ports , etc . You get the drift .
The
advantage of this approach is that we then have an immediately usable box of
tools to analyze and suggest fruitful new approaches .
Our
electricity networks would also gain , since evolution has been at this problem
for a tad longer than humans .
Melatonin
for ESKOM ? Some would say they are asleep at the switch in any case .
Throttles .
There seems
to be a wee problem here .
The problem
seems to be too much energy , not too little .
Most
organisms normally spend 1/9 to 1/3 of 24 hours actually getting enough to eat
. The rest is spent having fun or sleeping .
Sleep:
There is a
strong suspicion that melatonin throttles down the production of ATP , but not
the usage of ATP (cf fMRI scans of sleeping brains) See Appendix B . Sleep
would then be necessary to keep the organism out of trouble (ie quiescent) while
surplus ATP is used up . (1/3 : eg 8 hours per day)
Obesity
epidemic:
As can be
seen from the above , the problem is not a sudden influx of energy-rich food
.This has been a trouble since the first mitochondrium took up housekeeping in
a host cell .
The obesity
is caused simply by a lack of sleep .
Present
generations sleep less . Artificial lighting , computers , cinema , etc . The
extra waking time is also usually spent eating .
The
equilibrium is upset . (This has been going on for about 100 years on a large
scale) .
An
interesting result is the generational increase in IQ measurements . The system
is trying to soak up the extra energy in more complex nervous structures (for
which it has the evolutionary tools) . An epigenetic feedback loop is suspected
.
Kids who
stay up late for three generations will be fatter and smarter .
Diabetes .
Melatonin
has many effects . Lack of it causes neuro-degenerative complications (see
Appendix B) . Included is peripheral neuropathy . This is where we can use our
useful little model of an electricity grid above . Without the feedback from
the damaged nerves , the system cannot shift loads . Just monitoring the
glucose level is too coarse. Fluctuations build up . Future load estimations
cannot be made . Fat builds up .
Old Age
Lack of
sleep during old age leads to glucose metabolic complications for all the
reasons mentioned , regardless whether the person is obese or not .
Other
throttles are rendered less effective by lack of materials:
Specifically
, sulfur (H2S hibernation throttle) , chrome (cytochrome oxidase : see Appendix
B) , alpha lipoic acid(nerve repair) , melatonin .
Homeostasis
is another useful little energy soak .
Large brains
ditto .
But Culture
, hot or cold , is master of them all .
Nothing
soaks up energy like culture . Fashion is by far the largest industry on the
planet , outstripping even food production .
Eg sports is
a fashion . Clothes .Entertainment . Tourism . Even lies . (JK Rowling is the
most fashionable and richest professional liar in Britain .)
What is the
culture of your mitochondria ?
An Actual ,
Physical ATP generator you can buy .
This is a
well-known and clinically proven machine usually touted for pain-relief .
It works .
But the
theory is rather patchy . There used to be a lot of mumbo-jumbo about the gate
theory of pain .
It actually
works by alleviating the underlying causes of the pain (see scans on website) .
It does this by pumping energy into the ATP-rotors from the outside at the
damage site .
It does this
by sending 3-millisecond square pulses which decay exponentially (see wave-form
on web-site .) This spins up damaged rotors and transfers energy (a non-food
source of energy) . Most importantly , it re-establishes timing mechanisms .
Cells on the point of mitochondrial apoptosis can be salvaged . (The apoptosis
mechanism is very sensitive , due to all the feedback mechanisms involved.)
While the
energy input here is small , the energy of an ATP molecule is not exactly large
. And the ATP is targeted exactly at the damage site . This helps to stop the
cascade effect of trauma-shock .
Your
attention is drawn to the well-known effects of aligned magnetic fields on
bone-healing . A similar thing happens here .
Notice the
effects of zero electro-magnetic fields on early astronauts .(Their metabolisms
went haywire) . They had to be supplied with artificial fields .
Speculations:
Energise
organisms directly by high-energy em-waves .
Are there
any like that already ? The planet is awash with em waves and organisms with
flagellae .
Deep ocean ,
moons of Jupiter or Saturn springs to mind .
An actual
cure for diabetes by re-establishing communications between cell-groups to do
proper load-sharing .
Also useful
for cases of paralysis or strokes .
Fat-loss
without dieting or exercising . Fashionable .
Targeted ,
too .
Spin up the
mitochondrial rotors with em-waves , then wash out the surplus ATP in urine
after fixing this ATP with something like a mono-clonal anti-body .
Get rid of
that cellulite !
Cheating at
sports . (Even more fashionable)
A focused
em-wave of the right form will boost ATP production of an athlete or horse at
that critical instant , and is nearly undetectable .
Muscle
building for the gym-brigade .
Eg the
machine for training the biceps can have an em-generator focused on the biceps
while training . Saturation by ATP will hopefully rapidly increase muscle mass.
MRI problems
.
As you will
have gathered , alignment of mitochondrial rotor-spins by a powerful magnetic
field as found in MRI machines can have unfortunate effects if the patient is
soon afterwards exposed to em radiation of periods of 3 milliseconds (or beats
thereof)
Melatonin
and DHEA supplements should form part of the old age package (like statins
, etc) .
Nanotech
should be able to do really interesting things .
And so it
goes round and round .
Andre
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Annexure
A
Sunday,
January 21, 2007
Almost incredibly, a
sedentary adult makes and uses 40 kg of ATP per day! ATP is made
by the F0-F1 ATPase, a molecular motor with a rotating shaft and fixed "stator".
One end of the shaft, F0, is buried in the mitochondrial inner membrane where
the proton gradient causes it to rotate. A single gamma subunit connects the F0
to three alpha and beta subunits, together F1, which are responsible for
synthesizing ATP from ADP and Pi (H2PO4-). As a catalytic motor and not
just a catalyst, the F0-F1 ATPase is able to increase the rate of reaction away
from the equilibrium (which strongly favors the reverse reaction, hydrolysis,
because the concentrations of reactants and product in mitochondria are
similar). The gamma subunit rotates too slowly, in the
microsecond-to-millisecond range, for standard molecular dynamics simulation.
To solve this, the authors applied "biasing forces" as the motor
moved and assumed these forces would not change the mechanism. Positively
charged amino acids on the gamma subunit attract negative amino acids on beta
subunit, producing smooth and efficient ionic coupling. Rotation of the gamma
subunit induces the opening of the beta subunits. The beta subunit closes
spontaneously. Synthesis is not the reverse of hydrolysis, explaining why high
concentrations of free ATP does not inhibit synthesis. Gao and colleagues
propose a detailed model of how the motor harnesses the proton gradient to act
against the equilibrium. Their quantitative model is based on the conceptual
“binding change mechanism” model proposed by Boyer, where ATP synthesis
proceeds by each beta subunit changing from “open”, weak nucleotide binding, to
“tight”, high affinity ATP binding, to “loose”, with the release of ATP. The
authors used this model to make accurate predictions about synthesis and
hydrolysis kinetics and they invite others to test their detailed model.
PubMed :Yi Qin Gao, Wei Yang and Martin Karplus, "A Structure-Based Model for the Synthesis and Hydrolysis of ATP by F1-ATPase" Cell Oct 21, 2005; 123(2):195-205
PubMed :Yi Qin Gao, Wei Yang and Martin Karplus, "A Structure-Based Model for the Synthesis and Hydrolysis of ATP by F1-ATPase" Cell Oct 21, 2005; 123(2):195-205
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Annexure B
Melatonin, mitochondria, and cellular bioenergetics.
Acuña-Castroviejo D, Martín M, Macías M, Escames G, León J, Khaldy H, Reiter RJ.
Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Spain.
Aerobic cells use oxygen for the production of 90-95% of the total amount of ATP that they use. This amounts to about 40 kg ATP/day in an adult human. The synthesis of ATP via the mitochondrial respiratory chain is the result of electron transport across the electron transport chain coupled to oxidative phosphorylation. Although ideally all the oxygen should be reduced to water by a four-electron reduction reaction driven by the cytochrome oxidase, under normal conditions a small percentage of oxygen may be reduced by one, two, or three electrons only, yielding superoxide anion, hydrogen peroxide, and the hydroxyl radical, respectively. The main radical produced by mitochondria is superoxide anion and the intramitochondrial antioxidant systems should scavenge this radical to avoid oxidative damage, which leads to impaired ATP production. During aging and some neurodegenerative diseases, oxidatively damaged mitochondria are unable to maintain the energy demands of the cell leading to an increased production of free radicals. Both processes, i.e., defective ATP production and increased oxygen radicals, may induce mitochondrial-dependent apoptotic cell death. Melatonin has been reported to exert neuroprotective effects in several experimental and clinical situations involving neurotoxicity and/or excitotoxicity. Additionally, in a series of pathologies in which high production of free radicals is the primary cause of the disease, melatonin is also protective. A common feature in these diseases is the existence of mitochondrial damage due to oxidative stress. The discoveries of new actions of melatonin in mitochondria support a novel mechanism, which explains some of the protective effects of the indoleamine on cell survival.
Publication Types:
· Review
PMID: 11270481 [PubMed - indexed for MEDLINE]
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