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Parkinson's disease begins as an PHOTOelectrical defect.......

Discussion in 'Educating Doctors' started by Jack Kruse, Jan 6, 2019.

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  1. Brod Northwood

    Brod Northwood New Member

    Hi Brett, yeah I forgot to mention we are eating the canned sardines. Some times they are available fresh. Like you I have not been a big fan of seafood, except fish and chips. But since following Jacks way I have gradually taken the plunge.
     
    dantothep and Brent Patrick like this.
  2. Jack Kruse

    Jack Kruse Administrator

    Two PD-linked genes – parkin and PINK1 – have been implicated in mitochondrial quality control, via the degradation of dysfunctional mitochondria by autophagy (a process termed mitophagy). This suggests that the mitochondrial dysfunction observed in PD may be the result of compromised mitochondrial quality control mechanisms to recycle poorly functioning mitochondria. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715719/
     
  3. Jack Kruse

    Jack Kruse Administrator

  4. Jack Kruse

    Jack Kruse Administrator

    What if I told you that many if not most of the reactions at the tissue level work via an oscillation effect via your mitochondria in that tissue to change the oscillation using geometry in the cell to drive a chemical metronome process. Would you believe it?



    Is the secret to life-based in how a cell uses entropy?

    What if I told you the oxidation state of proteins is the chemical metronome for tissues and their colony of mitochondria. What if I went further and said this change in redox state is actually what changes the metabolic rate in a pattern that is picked up by how mitochondria operate over a 24 hour period.

    Would you believe it?

    What if I went further and told you that this might be behind why neurodegeneration patterns seem so similar yet they are different?

    Are their different protein water systems that oscillate at different resonant frequencies in tissues to account for this.

    Is this how cells break symmetry and use chaos?

    Most of you know I believe life is lived at a position far from equilibrium. A cell is never at equilibrium until it dies. Being far from equilibrium means al cells have to have a chemical metronome at some level.

    Some far-from-equilibrium reaction systems exhibit an oscillating behavior that involves amplitude or periodic changes in the concentration of some ingredients in space or with time. Such systems are often called oscillating chemical reactions. The oscillating chemical system is interesting because it may serve as a simple chemical model of biological processes, such as heartbeat, breath, even the sleep cycle. What happens when these systems fall back to equilibrium?

    Disease ensues and mitochondrial biology changes. So do its geometry and alignment in a cell. Its energy and information output in free radicals change and this changes the redox state of the cell. Thereby ruining the chemical metronome.

    Many researchers have studied most of such reaction systems and proposed theoretical models accounting for the experimental results from the physicochemical point of view in order to elucidate the complex reaction mechanisms.

    Recently, the application of oscillating chemical reactions for the determination of trace amounts of substance has gained some interest from the analytical chemists because of its instrumental simplicity and high sensitivity.

    The well-known oscillating chemical systems are the Belousov–Zhabotinskii (BZ) reaction and the copper-catalyzed oscillating system is one such reaction. It was found by Boris Belousov when he was trying to figure out how cells made energy from glucose. He actually stumbled into the butterfly effect of biochemistry that occurs with some of the anions in the mitochondrial matrix. For a Black Swan, his work is one of the most fascinating rabbit holes in your journey to travel. The video above is a simulation of the BZ effect but it makes the point of what an oscillating system does.

    For the analytical purpose, the most extensively studied oscillating reaction system used is the Belousov-Zhabotinskii (BZ) reaction, which involves the oxidation of malonic acid by bromate ion (Br-) in acid media and catalyzed by traces of transition metal ions that possess two oxidation states differing a single electron, whether in free form or as complexes. When the BZ reaction occurs, a regular potential oscillation (with time) can be recorded through an electrochemical instrument. Belousov first saw this as a color change in the reaction from clear to yellow and then back again from yellow to clear with no additional energy added to the experiment. This stunned him. The paradigm did not believe him and he quit science in the 1950s.

    Why did I get so intrigued by the BZ reaction? I found out that humans had no GULO gene to make our own Vitamin C, but we did have the possibility of a BZ reaction in our mitochondria using ascorbate in a cyclic fashion. If it was used this way we would not need much an exogenous source if the mitochondrial biologic balance of autophagy and apoptosis remained relatively intact. I was stunned by this insight.

    Many previous studies in analytic chemistry have shown that many organics such as polyphenols, hydroquinone, benzidine, ninhydrin or ascorbic acid can perturb the BZ reaction in a linear manner, with concentrations or logarithm of concentrations. I think this is why Szent Gyorgi and Pauling where so INTRIGUED with vitamin C in their work done on the Kreb cycle inside the mitochondrial matrix. I also think that deuterium concentrations within Krebs' bicycle interrupt the normal BZ pattern of ascorbate inside the TCA cycle anions to change the flux rate.

    These results all indicated to me that B-Z reaction cannot only be a useful analytical tool for the direct determination of trace amounts of organic compounds, but it may help us understand how life organizes and operates using entropy and chaos to organize via the butterfly effect. Does this explain how symmetry is broken to drive tissue level morphogenesis using an oscillating chemical metronome?

    I also realized that the use of BZ reaction would be important in mitochondria for determination of metallic ions and how they would change physiologic parameters inside tissues using incident light EMF's. This idea has been much less been reported on in analytic chemistry but there are guys like Mike Levin at Tufts working ion gated changes altering electric and magnetic fields in cells to explain cellular size and shape changes which drive topologic changes in cells.

    The story of 21st Century biology has, thus far, been about gene expression. It is a fatally flawed paradigm ideal, to be frank. Becker showed its cracks long ago. The paradigm believes that the body is controlled by chemical signals, and these are produced on demand by masking and unmasking different portions of the chromosome, exposing the code for the proteins that are needed in a given cell at a given time. Our activity and our homeostasis are maintained in this way from moment to moment, and I believe that our life histories, from development to aging and death, are also controlled via gene transcription.


    Now Levin's group at Tufts has demonstrated that, at least under some circumstances, there is a system upstream of gene transcription that is based on electric circuits. What is upstream of these circuits? SUNLIGHT! Levin has zero clue that the system is controlled by light.
    The system controls development at a level higher than gene transcription. For example, an entire eye can be ordered up by artificially creating an electric pattern in the right place, and the eye will have all its parts intact and be functional. This seems to run by some electrical chemical metronome. My bet is that eventually it will be shown to be a BZ reaction. Levin's group has actually placed eyes on a tadpole’s tail and demonstrated that the tadpole can see through them, and their brains can interpret the images.

    The interesting part is how they did it using metal ions. This is another signature of the BZ reaction. In living fluids, within and between cells, contain dissolved salts in the form of positive (Na+, K+, Ca++, Mg++) and negative (Cl–, PO43-, SO42-) ions, Cell membranes have pumps that can pump ions out of the cell selectively and ion channels that allow some ions through, but not others. The paradigm knows drugs can affect these channels but they are just waking up to the fact that light can do it too.
    Typically, the living cell has more negative than positive ions inside, so it has a negative membrane potential, ranging from a few mV for blood and skin to tens of mV for nerve and muscle cells. Pollack extended this idea with the net negative charge of the EZ. This process also uses light. This is likely the key to the wireless control of the BZ system in cells. The rapid changes in membrane potential we see in the lab appear to be the driving force behind muscle contraction and nerve firing.

    Here is where it gets interesting. Mitochondria are the most negative parts of the cell, They average a voltage at about -140 mV. It can vary based upon redox power which is linked to geometry according to Wallace's work.

    How do researchers use cells to manipulate electric patterns experimentally, to demonstrate the effect on morphology?

    From Levin's work, it is clear it is not done with external electric voltages. It is done with biochemical modification of the gateways that control ion channels. Levin has said that there are photo-sensitive drugs that can control ion gates that can be used to translate a projected geometric image into a pattern of membrane potentials. This is another fingerprint that a BZ like reaction is critical in cell biology. I have a deep sense this is linked to ascorbate as an electron donor in the mitochondria to alter and varying the mitochondrial charge ENDOGENOUSLY.

    Levin has argued in many papers (28 listed on his website) that the patterns encode “blueprints” rather than a “construction manual”, based on the fact that the program is adaptive in the face of physical barriers and disruptions, and organisms are capable of detecting damaged parts and growing new parts to the original specs.

    Levin’s group has tampered with membrane potentials in order to guide the growth of nerve axons in regenerating tissue. It appears this is just the beginning of paradigm change that links back to Turing and Belousov work in the 1950s on morphogenesis which uncovered the true essence of the non-linear nature of equilibrium in the living state.

    It appears to be linked to the butterfly effect caused by the BZ reactions of the mitochondria. This changes the oscillation rate of the mitochondria and that changes the voltages. This will be the driver of modern cell biology for topologic changes when we understand that mitochondrial redox power is ultimately necessary to reprogram electric circuits to order for physiologic processes such as healing and clotting to occur on time. It might be the holy grail of controlling healing and wound regeneration in future medical applications that Robert O. Becker stumbled into in the 1960s with his salamanders and human bone regeneration.
     
  5. Jack Kruse

    Jack Kruse Administrator

    Levin gave a recent talk at Stanford about his work.



    The last ten minutes of this video by Wallace links the oscillation geometry to the BZ equation.

     
  6. Jack Kruse

    Jack Kruse Administrator

    Cortical neurons require glutamate containing cells that make GABA but guess what their partner glial cells also release during a stressor stimulus?

    Vitamin C.

    [​IMG]

    When a mitochondria makes this decision it changes the endogenous electric signal............
     
  7. Jack Kruse

    Jack Kruse Administrator

    The irony was Belousov and Turing work was almost identical........but showed different facets of the butterfly effect at operational levels in biology.

    The BZ effect was predicted by Turing's equations in his 1952 paper on morphogenesis.

    After Belousov quit science and Turing's suicide in the 1950s many other scientists showed that many reactions if placed in a petri dish began to magically lead to self-organization. They went beyond Turing's blobs and stripes he mentioned in his paper. They lead to highly complex behavior as we see in water and protein networks in neurodegeneration models.

    These patterns seem to come from nowhere just like neurodegeneration. Our heartbeat in the same way..........

    Chaos allows for some very simple equations with nothing random in them leads to some very interesting things. In these equations, we know everything about them. Everything is determined. These equations, however, can lead to outcomes that are entirely unpredictable. Edward Lorenz, a meteorologist forced the idea of chaos in science and it was what took the Newtonian paradigm down.

    His paper was about chaotic weather patterns that defined non-linear and non-equilibrium states. He tried to find math equations to help determine the weather.

    He wrote down simple math equations that determined air current and he found out that none of the air currents did what the equations said they should do. In fact, his equations made no useful predictions whatsoever. ==== butterfly effect

    In 1970s Robert May studying the mathematics of animal population growth changed over time found Lorenz butterfly effect in his own work.

    This ended Newton's belief paradigm that an equation was deterministic about anything in nature. Even though Newton got us to the moon..........Lorenz, May, Turing, and Belousov all showed us nothing in biology is Newtonian. In the 1960s the belief was as we got more computer power we would easily be able to solve the more complex problems. It turns out that failed too.

    It seemed Nature, especially biology was all NON-Newtonian. Newtons clockwork universe was a giant illusion of scientism. This logical certainty turned out to be an act of faith.

    Chaos is everywhere and nature hardwires it into everything. Then Mandelbrot showed up and proved it beyond a shadow of a doubt when he innovated fractal geometry.

    Mathematics can describe nature with a simple equation but it can never explain it because of the effects of small things in these equations lead to unpredictable results. This is when Turing and Belousov work began to be appreciated.

    This idea links to order and chaos in nature because it leads to patterns and topology.

    Small changes in free radical signaling or the isotope of hydrogen in mitochondria could lead to tissue formation in an animal. These small changes altered the way matter organized in health and diseases states.

    The mathematics of chaos rules are simple but always involve coupling or a feedback mechanism. For cells that feedback mechanism is based upon light and dark.

    A picture in a picture in a picture is an example of a feedback loop and this is exactly what a fractal does. A fractal is a self-similar geometry found in nature. Self-similar things can undergo small quantum changes and this leads to a pattern, and size and shape change. This leads to chaotic behavior and pattern behavior.
     
  8. Jack Kruse

    Jack Kruse Administrator

    The Mandelbrot set is the basis of fractals. All of nature's complexity comes from one simple equation

    Z = Z^2 + C the = sign is reversible and this allows the equation to feedback on itself. Each output (Z) becomes the input for the next coupled cycle (Z^2)

    All of nature's organization is based upon this set. This means protein misfolding is tied to small changes that lead to its chaos and it aberrant physiology.

    A complex system can be based on simple rules. This is the big revelation of chaos.

    This means diseases and wellness operate in the same way but the small differences in the quantum spin state are what determines the complexity of the disease. It alters the fractal pattern of organization. This means that the mitochondria of the cell are a cell simple rule.......but the way it changes its handling of electrons and protons with incident light waves is enough variation to lead to complexity of disease phenotype.

    This applies in mitochondria and in all of nature.

    This change without much change even drives evolution, in my opinion.

    It also explains how diseases come from wellness when small things in our environment vary.
     
  9. Jack Kruse

    Jack Kruse Administrator

    Back to the BZ reaction Vitamin C and lactate and glucose.

    Pyruvate is the end-product of glycolysis, a major substrate for oxidative metabolism, and a branching point for glucose, lactate, fatty acid and amino acid synthesis.

    Pyruvate is a critical intermediate that can be used in a variety of anabolic and catabolic pathways, including oxidative metabolism, re-synthesis of glucose (gluconeogenesis), synthesis of new lipids (de novo lipogenesis) and cholesterol synthesis, and maintenance of the tricarboxylic acid (TCA) cycle flux. Pyruvate metabolism for these processes requires mitochondrial import, which is a carrier-mediated and regulated process.


    Pyruvate can be created from several sources in the cytosol. A predominant source is from the breakdown of glucose through anaerobic glycolysis into two molecules of pyruvate, ultimately produced by the enzyme pyruvate kinase. A significant proportion of pyruvate is produced via oxidation of lactate by lactate dehydrogenase. Pyruvate can also be re-formed from malate by cytosolic malic enzyme, which plays an important role in shuttling mitochondrial TCA cycle metabolites such as citrate, malate and oxaloacetate between the cytosol and mitochondria. One last significant source of pyruvate is from the catabolism of three-carbon amino acids. Alanine transaminase (ALT) catalyzes the reversible reaction of alanine and 2-oxoglutarate into glutamate and pyruvate. There is also a component of ALT activity in the mitochondrial matrix, and alanine can be transported into mitochondria and then converted to pyruvate. Serine, threonine, glycine, cysteine and tryptophan can all be converted to pyruvate as well. Altogether, these comprise the primary sources of cytosolic pyruvate.

    What determines which path is taken? I think it is the amount of Vitamin C and deuterium in the mitochondria. This is the mitochondrial Circumstance for its BZ reaction.

    PD is a muscle disease because of the link to dopamine to muscle fiber type.
    pyruvate can also be reduced to lactate by the bi-directional cytosolic enzyme lactate dehydrogenase (LDH), of which there are two distinct isoforms: LDH-A which favors the production of lactate from pyruvate, and LDH-B which favors the production of pyruvate from lactate. LDH-A is also known as the M isoform (for muscle), whereas LDH-B is alternatively referred to as the H or heart isoform. Appropriately, glycolytic skeletal muscle is a robust lactate-producing tissue, whereas the heart is a pyruvate-oxidizing organ.

    Our current understanding is that two proteins, mitochondrial pyruvate carriers MPC1 and MPC2, form a hetero-oligomeric complex in the IMM to facilitate pyruvate transport and they use protons to carry out their ability to get pyruvate into the mitochondria. (Key in the BZ reactions and its interactions with Vitamin C)

    Pyruvate can be formed in the cytosol by glycolysis, or conversion from alanine by ALT, from lactate by LDH-B or from malate by malic enzyme (ME).
     
  10. Jack Kruse

    Jack Kruse Administrator

    Everything is reversible, but not every person is fixable because they refuse to change their environment to regain wellness. You cannot change what you refuse to confront. Removing bad habits, and poor environments are far more effective than removing organs. The world is not changed by your opinion, but it can be changed by our actions and the example we set. #mitochondriacwisdom

    [​IMG]
     
  11. Jack Kruse

    Jack Kruse Administrator

    Back to the BZ reaction Vitamin C and lactate and glucose.

    Pyruvate is the end-product of glycolysis, a major substrate for oxidative metabolism, and a branching point for glucose, lactate, fatty acid and amino acid synthesis.

    Pyruvate is a critical intermediate that can be used in a variety of anabolic and catabolic pathways, including oxidative metabolism, re-synthesis of glucose (gluconeogenesis), synthesis of new lipids (de novo lipogenesis) and cholesterol synthesis, and maintenance of the tricarboxylic acid (TCA) cycle flux. Pyruvate metabolism for these processes requires mitochondrial import, which is a carrier-mediated and regulated process.


    Pyruvate can be created from several sources in the cytosol. A predominant source is from the breakdown of glucose through anaerobic glycolysis into two molecules of pyruvate, ultimately produced by the enzyme pyruvate kinase. A significant proportion of pyruvate is produced via oxidation of lactate by lactate dehydrogenase. Pyruvate can also be re-formed from malate by cytosolic malic enzyme, which plays an important role in shuttling mitochondrial TCA cycle metabolites such as citrate, malate and oxaloacetate between the cytosol and mitochondria. One last significant source of pyruvate is from the catabolism of three-carbon amino acids. Alanine transaminase (ALT) catalyzes the reversible reaction of alanine and 2-oxoglutarate into glutamate and pyruvate. There is also a component of ALT activity in the mitochondrial matrix, and alanine can be transported into mitochondria and then converted to pyruvate. Serine, threonine, glycine, cysteine and tryptophan can all be converted to pyruvate as well. Altogether, these comprise the primary sources of cytosolic pyruvate.

    What determines which path is taken? I think it is the amount of Vitamin C and deuterium in the mitochondria. This is the mitochondrial Circumstance for its BZ reaction.

    PD is a muscle disease because of the link to dopamine to muscle fiber type.
    pyruvate can also be reduced to lactate by the bi-directional cytosolic enzyme lactate dehydrogenase (LDH), of which there are two distinct isoforms: LDH-A which favors the production of lactate from pyruvate, and LDH-B which favors the production of pyruvate from lactate. LDH-A is also known as the M isoform (for muscle), whereas LDH-B is alternatively referred to as the H or heart isoform. Appropriately, glycolytic skeletal muscle is a robust lactate-producing tissue, whereas the heart is a pyruvate-oxidizing organ.

    Our current understanding is that two proteins, mitochondrial pyruvate carriers MPC1 and MPC2, form a hetero-oligomeric complex in the IMM to facilitate pyruvate transport and they use protons to carry out their ability to get pyruvate into the mitochondria. (Key in the BZ reactions and its interactions with Vitamin C)

    Pyruvate can be formed in the cytosol by glycolysis, or conversion from alanine by ALT, from lactate by LDH-B or from malate by malic enzyme (ME).
     
  12. Jack Kruse

    Jack Kruse Administrator

  13. Sajid Mahmood

    Sajid Mahmood Mo Salah

    Can get hold of organic farmed salmon. What’s your opinion on them? Wild is always my first priority though. Love the taste of wild sockeye salmon
     
    Last edited: Jan 16, 2019
  14. Jack Kruse

    Jack Kruse Administrator

    I like them.....but for an equatorial guy in the UK you know what I am saying matters most right?

    I may be coming to the UK this August FYI.
     
  15. Sajid Mahmood

    Sajid Mahmood Mo Salah

    Do you think building a 5G proof home near the beach maybe a good idea in a 5G world?
    In a 5G world, maybe there will be significantly less nnEMF on the seaside. Not sure though
     
  16. Sajid Mahmood

    Sajid Mahmood Mo Salah

    Yeah I understand. That should be my number one priority right now before anything else. You definitely need to come to the UK. Would love to meet you!!
     
  17. Jack Kruse

    Jack Kruse Administrator

    Everything in my thesis is beginning to fit............

    The parabiosis longevity link = astrocytes loaded with Vitamin C = biologic Belousov effect.
    MANF (mesencephalic astrocyte-derived neurotrophic factor) is one of the factors responsible for rejuvenating the transfused older mice according to new research. Shocking no one who reads biophysics.

    We know that MANF regulates metabolism and immune response in flies, mice, humans. what they forgot is that none of them can make their own Vitamin C either.......hence why the parabiosis effect is an RBC's effect.

    The myopia of researchers amazes me. Buck Institute needs smarter people working there.

    https://www.buckinstitute.org/news/manf-identifed-as-a-rejuvenating-factor-in-parabiosis/
     
  18. Jack Kruse

    Jack Kruse Administrator

    For a guy like you in the UK, I don't think I want to see you anchored where you should not be.

    Right now you are a cactus in the tundra.

    Not bueno.
     
  19. Sajid Mahmood

    Sajid Mahmood Mo Salah

    How about the Canary Islands at the 28th Latitude? Good enough?
     
  20. Jack Kruse

    Jack Kruse Administrator

    The Cori cycle (also known as the Lactic acid cycle), named after its discoverers, Carl Ferdinand Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized back to lactate. See where glucose and lactate are in the blood below where those RBC's are. This is where Vitamin C is doing the magic in my opinion in a BZ like reaction. Many small thinkers think the brain needs glucose but few of them realize neurons really like lactate. When you use lactate over glucose what do you preserve in the RBC's? Vitamin C.

    [​IMG]

    This cycle is also important in producing ATP, an energy source, during muscle activity. PD affects muscles and neurons predominately so the defect for this diseases cross The Cori cycle functions more efficiently when muscle activity has ceased. I have a deep sense this is why motor neurons are MADE defective in PD. They are trying to reserve lactate for the ailing dopaminergic neurons. As the disease progresses the motor symptoms become much more prominent. Why would nature do this? This allows the oxygen debt to be repaid metabolically such that the Krebs cycle and electron transport chain can produce energy at peak efficiency in neurons. Since PD neurons have defective mitochondria nature is looking to find a way out of this chaos.

    Metformin is used in anti-aging circles and in neurodegeneration to bypass defective cytochromes. It can cause lactic acidosis in patients with renal failure because metformin inhibits the hepatic gluconeogenesis of the Cori cycle, particularly the mitochondrial respiratory chain complex 1 NAD+/NADH couple. The buildup of lactate and its substrates for lactate production, pyruvate, and alanine, lead to excess lactate in the mitochondria. When the anions in the Krebs bicycle are gunked up with the KIE of deuterium this becomes a pathway of success. Anti-aging docs are looking to bypass a defective matrix but few of them realize it. This blockade also is associated with a loss of Mg when you use it chronically in PD or diabetes or aging.

    Normally, the excess lactate would be cleared by the kidneys, but in patients with renal failure, the kidneys cannot handle the excess lactic acid.

    So why would Nature want to build up lactate and alanine?

    Simple.......it is how she plans of fixing cytochrome one when autophagy or apoptosis are nonfunctional.

    How?

    Have you ever hear of the Cahill cycle? It is known as the alanine cycle or glucose-alanine cycle. It is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is one of the other cycles that meet at Kreb's bicycle. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver.

    When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose. Remember glucose is an aldehyde carbohydrate and very similar to Vitamin C structure.

    The Cahill cycle is less productive physiologically than the Cori cycle unless heteroplasmy is RAISED. The use of lactate is a byproduct of energy production from alanine is a production of urea. Removal of the urea is heavy energy-dependent so a sic colony of mitochondria wants to avoid urea like nuts. Using urea requiring four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP), thus the net ATP produced is less than that found in the Cori cycle.

    So why would nature use the urea cycle to handle proteins if cytochrome one was shot as it is in PD and diabetes? However, unlike in the Cori cycle, NADH is conserved because lactate is not formed. This allows for it to be oxidized via the electron transport chain to move high energy electrons and make superoxide free radicals again.

    Lactate is considered an important metabolite in the human body, but there has been considerable debate about its roles in brain function. Research in recent years has suggested that lactate from astrocytes may be crucial for supporting axonal function, especially during times of high metabolic demands or hypoglycemia. The astrocyte-neuron lactate transfer shuttle system serves a protective function to ensure a supply of substrates for brain metabolism, and oligodendrocytes appear to also influence the availability of lactate. There is increasing evidence for lactate acting as a signaling molecule in the brain to link metabolism, substrate availability, blood flow, and neuronal activity.

    Muscles generate the greatest amount of lactate in the body. Lactate is moved within and between organs by monocarboxylate transporters (MCTs). When pyruvate is converted to lactate there is a change in oxidation state as lactate is more reduced than pyruvate. The redox change acts as a mitochondrial signal within the cell and inhibits the consumption of other substrates. It seems possible that lactate has an effect on mtDNA and DNA gene expression as it is also linked with mitochondrial biogenesis stimuli and modification of MCTs. This appears broken in PD neurons.
     
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