WHY IS MOLECULAR CROWDING A BIG DEAL IN ALL OF THIS?
By adopting a more simplistic experimental framework, their tests may be neglecting one critical aspect of biological systems in flux when energy is being lost: the crowdedness of the cell. We know molecular crowding of cells is directly tied to temperature and timing variables in biologic systems. Moreover, these factors are rarely studied as part of the experimental design process. I mentioned this fact in Cold Thermogenesis-6. This is why most of this information remains outside the perception of modern science. If you don’t perceive it, you don’t think to control for it. In other words, you are unaware of what you might not know. When that fact turns out to be this important; you have a large problem when drawing conclusions. Well, folks we have a large problem because of it.
As an analogy, think about trading a real living cells size for a labs test tube. The spaciousness of a laboratory test tube can be as stark a transition as leaving a a New York City loft for a wide-open South Dakota ranch, in terms of population density. So how does molecular timing being off, effect molecular crowding, you ask?
When timing is off we lose electrons from the electron chain transport in the mitochondria. This loss leaves “space” between electrons. This space time defect throws off the nano-scopic precision in the mitochondria and we lose massive amounts of energy in ATP because of it. When ATP is lost, the result is that a cell’s interior gets positively charged and more crowded because it swells and it become more permeable to further positive charges rushing in the electrochemical gradient established by the ATPase. Remember electrons come from food and the magnetic field.
A mitochondria normally leaks 2-5% of its electrons at cytochrome 1 for normal mitochondrial function and activate or deactivate telomerase, which controls our telomere lengths. Telomere lengths are directly proportional to our longevity according to the the 2009 Nobel Prize winner, Dr. Blackburn. When we leak more at the mitochondria, the science says we first create crowding, and then we swell, get inflamed, and we age faster and die sooner. Truth Bomb.
GEEKS UNITE: How does alteration in space/time lead to inflammation? One obvious result of a crowded intracellular milieu is there is less available space for each molecule to exist, which increases the effective concentration required to carry out the chemical reaction and it reduces its chemical potential. This is precisely why the kinetics of chemical reactions change when timing is altered. The reaction results maybe the same, but if they are frame-shifted because of the alteration of timing just studying the biochemistry alone does you no good. Products of one reaction need to be available for another and when they are not chaos is the result. This is why what is published in the literature in many cases maybe worthless.
This may explain why nutritional and biochemistry research will never elucidate the answers we are all looking for. They never control for temperature or for circadian timing errors in their experiments, yet, we see examples all over chemistry how these two variables dramatically alter experimental results. The results of timing errors in mammals leads to changes in their hormone status because of the loss of electrons causes inflammation. Research already has shown that humans with altered melatonin levels get sicker quicker, have memory loss, cognitive problems, and get epithelial cancers. It should make intuitive sense why this happens now. Moreover, it implies that research done on them, is going to offer different results than those done on people with adequate melatonin cycles. A low melotonin status tells us we have higher ROS present in the central nervous system. Melatonin is the most potent anti-oxidant in the brain followed by oxytocin and DHEA.
Lowered ATP = Leptin resistance = low melatonin = low brain dopamine levels = upside progesterone to estradiol levels = low testosterone levels = low vitamin D levels. Got it? Your hormone panel becomes train wreckish and its results, becomes the Rosetta Stone of telling the clinician how bad the Rolex in our head is in telling time from the environment.
As time elapses, these alterations in timing, in combination with slower photo-electric speeds, cause a lack of electrons delivered to the mitochondria, as a result. Low levels ATP production change the inner mitochondrial membranes potential and alter the efficiency of oxidative phosphorylation because we do not make enough ATP to keep our batteries charged. When timing is off we get more ROS generation from the cytochromes than the normal 2-5% we spoke about in the January 2013 webinar. As a result, the mitochondria make even less ATP, and when more time elapsed it increases the space/time deficit, this alters physiologic function of organs when we fall below 60 kJ of energy production from the mitochondria. Nomally from one mole of water we normally make 286 kJ of energy. Over a life time of bad circadian timing, we lose that power differential more quickly when artificial light and EMF signals dilate space/time and alter electron flow in our mitochondria. It takes about 25-30 years for a good mitochondrial to decline from 286 KJ to 60 KJ based upon my math skills, give or take a few years. Are you beginning to see why kids are more obese and sicker today than at any other time in history? Timing is a big deal for biology. It also explains the NHANES shifts.
ORGANIC CHEMISTRY GEEKS: As less ATP is made, molecular crowding worsens rapidly. As more electrons are lost, the electron chain has more “potential gaps” and space/time bends more and more and we age at faster and faster rates. This is exactly what we are seeing today on this planet. This erodes mitochondrial efficiency further. As a result of lowered ATP levels, more molecules are squeezed into the cell because the cell membrane becomes more permeable it loses its charge as energy levels decline. We leak more calcium into the cell. As more electrons are lost the mitochondria become more positive. The more positive they become the greater the electrical gradient becomes to create ROS and inflammation. As it continues, you’re improving the chances that the mitochondria fail and as time elapses. As time evolves it happens earlier and earlier in the species in question. This is why diseases of aging now show up in teenagers. Recently we learned that mitochondria fail in eukaryotes when the lysosome/vacoule located adjacent to them become more alkaline and less acidic. This work was just published in November 2012 from the University of Washington.
This pH change alters mitochondrial function to replenish itself with things it needs according to this latest research. Ironically, the pH gradient is also maintained by adequate ATP levels from the mitochondria, so it has a built in feed back switch for mitochondria signaling for biogenesis or apoptosis and telomere biology. It is really an exponential relationship in the mitochondria; if you toss in a few more positively charged reactants into the mix that decrease electron flow for any reason at all (think carbs out of season or a low Mg level), the chemical potential responds dramatically and further reduces energy production because the effect on the electron chain.
Another effect of molecular crowding is a slowdown of molecular diffusion, particularly for large molecules. ATP happens to be a large molecule. All ATP in the cell has to have magnesium bound to it, for it to work the ATPase. The telomerase enzyme is also magnesium dependent. This Mg binding makes ATP even bigger in molecular size and this slows the chemical potential further causing more alterations in space/time. So if the cell is more crowded and your energy source is a large molecule it will slow all biochemical reactions down even further, as the gradient to make ATP declines further.
Think of this analogy: Imagine moving through a toy store collecting large stuffed animals constantly, propelled by an unwavering need to snap them all up for your daughter’s upcoming birthday. After a short amount of time the load is large and your can’t move fast through the store. Lower rates of diffusion mean that diffusion-limited reactions will happen much slower, especially those involving larger constituents.
Slower biochemical reaction rates means timing is off and your hormone panel shows evidence of it. What else is present? Inflammation is the result of timing chaos. This is why inflammation (hs-CRP) is the real etiology behind all altered hormone panels and all neolithic diseases. The presence of cellular inflammation is the ultimate scientific proof that this is precisely what is happening. Can we see it?
Yes, when we use lab tests, thermograms, or functional MRI’s to look for inflammation in low energy states in you right now. It is too bad medicine does not use any of these effectively for real early detection of disease. If they understood this process they would be using thermography as a serious diagnostic tool for early mitochondrial dysfunction before disease has a foothold. Instead we waste time on colonoscopies and mammograms that show disease much later in its progression when organs have been suboptimal in physiologic function for a long time already. Early detection depends upon your idea of time relativity, I guess.
TRUTH BOMB ALERT NON GEEKS: We can measure that in the blood hormone panels, especially an altered salivary melatonin level, or seen in a plasma with a low zeta potential (low serum Q10 levels). Altered melatonin levels tell us about alterations in the big and small hand on our molecular clock, which is controlled by light and dark. A low zeta potential tells us about the second hand, and this is codified by the electro-magnetic cells in the SCN that codified by the Schumann resonance frequency of the Earth. This can be found by checking a person’s alpha wave frequency and amplitude on an EEG. Electro-negative ions increase the electro-negative capacity of our serum which increases our serums zeta potential. Inflammation carries an electro-positive charge and this reduces the carrying capacity of our serum. When the serum’s CoEnQ10 level is degraded by more positively charged particles in our blood, it stimulates the elevation of the interior pH of the lysosome that supports the metabolic function of the mitochondria. It also has massive effects on lipoproteins in solution of our blood. When mitochondria are young and able to make ATP well, the lysosome is designed to be quite acidic with a low pH. The pH of our serum can be sampled to assess health and this is why arterial blood gases, CO2 levels, and BUN/creatinine levels matter a ton to a clinician when inflammation is present.
We can also measure a disruption in the zeta potential by seeing how altered the alpha waves are being produced in the brain with an EEG. We use this in seizure patients but I think we should be using it in others too. Alpha waves normally have a regular slow rhythm and a high amplitude but these waves slow down even further when we drift to sleep to replenish ATP stores. People with altered melatonin levels or zeta potentials will always default to faster acting biologic pathways to replenish ATP they are lacking.
THE “BARRY” BOMB: Humans Zoo animals get sub optimal performance when they do things outside the design of the Ferrari. MovNat ideas for exercise is the evolutionary Rx for movement, in my opinion. Power and endurance athletes will feel they need glucose and fructose to replenish glycogen and power performance because they can not fully use the pentose phosphate pathway to replenish D-ribose to make ATP fast enough because they are doing things in their diet that only a zoo animal thinks is good. The longer molecular clock timing is off, the worse things get for these people. The magnitude of loss of electrons from heavy exercise can also disrupt the mitochondrial system as well. This is why many endurance athletes get cancer, sustain massive heart attacks at races, and succumb from it.
Think about “fit ” women who are cross fitters who wind up without a menstrual cycle, or a “fit” guy with 10% body fat but who also owns a flat lined cortisol level and can’t sleep. These people are constantly posting questions on paleohacks looking for answers. Guess what the number one answer is? Eat more carbs. Now you may see why they say it. They do not understand, why they believe it however.
The less ATP we are able to recycle longer term, implies more electrons are lost as time elapses in the electron chain transport in the mitochondria. When you live like a chimp, you also have to eat like one to support your ATP replenishment pathways because your timing is off and you cant wait for the D-Ribose system to maximally replace ATP. This is why endurance/performance athletes perceive they need carbs. Barry on my forum, myself, and many others, think a bit differently about this set of circumstances. I think it is time you ponder the implications here for yourself.
When you live in this manner long enough you deplete your body of electrons, mitochondria, stem cells, and you eventually shorten your telomeres and get sick then die. It seems however that even chimps know intuitively how best to recycle ATP by choosing where to sleep……….but we don’t seem too.
CHIMP ALERT: Speaking of chimps, sleeping, and ATP: David Samson and Kevin Hunt of Indiana University studied chimpanzee nesting and sleeping in Uganda. They thought that differences in microclimate between the canopy and the ground might explain where the animals prefer to sleep. The pair set up portable weather monitors in trees and on the ground near nests from August 2010 to January 2011 to test their hypothesis.
Samson and Hunt reasoned, in the American Journal of Primatology, that maybe chimps chose the ground because it is a cooler, less windy place to sleep. They found that chimps do like to sleep on the ground as much as possibleas opposed to the canopy. They speculated, chimpanzees sleeping in terrestrial nests, probably spend less time trying to keep their beds stable in the face of unexpected gusts and therefore probably sleep more soundly throughout the night. They went on to say, based on estimates of temperature, wind speed, humidity and chimpanzee body mass, the animals sleeping on the ground stay in “energy balance” while those sleeping in trees experience more thermal stress. I think the explanation is more simple.
The chimps slept where they got more free energy while they slept……from the Earth. In other words, when the chimps were grounded and cooled by the ground and not up in the trees. This allowed them to gain energy from the electrons to help their mitochondria recycle ATP better.
LDL/HDL, TG, PLATELET BOMB: Loss of long term ATP replenishment ability is also why we see major charge changes in our lipoproteins when we have lost our zeta potential in our serum. This loss of Q10 causes our lipid membranes in the lipoproteins to become more “sticky” and cause disease in arteries. This increased viscosity causes slower LDL uptake at its receptor in the liver. This allows the LDL to stay in our serum longer and become exposed to a more oxidized serum that has been depleted in the isoprenoid side chain protections of Q10. CoEnzQ10 has 10 isoprenoid side chains that protect our serum from oxidation. This is one of the way natural selection has helped us live when we are disconnected from electrons due to starvation or a loss of the magnetic field on Earth. Our nearest ancestors have lower amounts of side chains on their versions of Q10, because their brains are smaller and smaller energy hogs and require less for ATP. Isoprenoids are replenished by the NADPH reducing power of the pentose phosphate pathway. This is another way evolutionary form, meets function. Isoprenoids come from our Archaea kingdom ancestors we mentioned in EMF-3 , for those looking for the evolutionary links.
GEEK FEST TRUTH BOMB: Ironically, we also need NADPH from the pentose phosphate pathway (PPP) to restore our chemical reducing powers to synthesize Q10 in large amounts, because we use NADPH to make isoprenoids, like Q10 in the liver.
NADPH also powers the recycling of glutathione, as well. This maximizes liver detoxification and it protects all our cell membranes from lipid peroxidation/ROS damage. This is critical in the brain and muscles for performance. This is why Q10 is tied to the zeta potential of our serum. Increased utilization of NADPH for fatty acid biosynthesis will dramatically increases the level of NADP+, thus stimulating glucose-6-phosphate dehydrogenase (G6PD) to produce more NADPH. G6PD is the rate limiting enzyme for the PPP. NADPH is a potent competitive inhibitor of the enzyme. Thus, the ratio of NADP+/NADPH regulates the pathway.
This is another biologic reason carbs out of season, are big problem for our species. Carbs generate huge amounts of NADP, stimulating cells to have to replenish ATP faster, using the less efficient ATP-CP or glycolytic pathways. When it comes to power and endurance all tissues that need this extra power rely on the PPP. When muscle is being regenerated for any reason at all, the flux through the PPP is up-regulated unexpectedly. This is when ATP is maximally needed. The same is true for DNA and RNA synthesis. You can’t reproduce when your energy recycling sucks. This is why women with low body fat who exercise like mad get hypothalamic amenorrhea. It is also why guys with great bodies can have testosterone levels below a 90 year old guy. It is where both sexes who are fit get their infertility from. This is why these critical pathways are all tied together in unison. The physiologic quantitative importance for the production of NADPH for tissues actively engaged in biosynthesis of fatty acids and/or isoprenoids is huge.
Those tissues are the brain, liver, mammary glands, adipose tissue, and the adrenal glands. This may explain why when you are not a fat burner, you constantly live a life with ATP recycling deficits. This is also why any other mental, emotional, physical, or physiologic, or metabolic stressor can push you off the edge so easily.
This is how the life you live is determined from your mitochondria’s perspective, and not yours.
Your brain is the navigator, while your liver is your metabolic engine and your thyroid is just the gas pedal. You need your liver to replenish glycogen using the D-ribose pathway, and try not to use the glycolytic pathway with carbs, to see this performance upgrade. This is why it remains in the modern human blind spot.
The more you can’t tell the correct molecular time in your brain, the quicker your need ATP, the more you believe you need carbs to feel better. Feeling better is function of rapidly replacing ATP, not effectively restoring massive ATP stores chronically as we are designed too. Feeling this way is a sign of a low brain dopamine level, and living outside the fat burning pathways. I spoke in depth about this in the Dopamine Rx.
Human red blood cells are great model for those to study who think starches are safe in winter. They rely heavily on the PPP and D-Ribose to replenish glutathione using the reducing power of NADPH.
PPP TRUTH BOMB: High glucose/fructose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and pancreatic beta-cell apoptosis in the pancreas. This is what causes diabetes folks. If your time perspective is off and this is why the answer remains in our blind spot. This is why cycloset works too!!!
NON GEEKS: This is why carbs/glucose/fructose keep you from finding out that D-Ribose is the alternative fuel for ultimate performance. It is also why bad clock timing leads to diabetes, autoimmunity, and cancer. It helps explain why cycloset is helpful in restoring AM cortisol function and helping T2D in a fashion that INDEPENDENT OF INSULIN!!!! See, Taubes did miss this part of the insulin carb story too.