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TENSEGRITY #11 comments welcome here..............

Discussion in 'Mitochondrial Rx' started by Jack Kruse, Dec 4, 2014.

  1. Jack Kruse

    Jack Kruse Administrator

    Caroline said we need to slow down Yew.............she says she is getting sea sick on this rapid increase of blog bombs..........
     
    Clayton likes this.
  2. Christos

    Christos New Member

    Was looking into the PPP and its tie in to NAD+ production, the only pathway I can see is from the glycerol 3-phosphate shuttle which oxidizes NADH to NAD+. On the topic of SIRTS, i found this abstract:

    Abstract:
    The most common enzyme defect in humans is glucose-6-phosphate dehydrogenase (G6PD) deficiency, which affects more than 400 million people. G6PD shunts glucose into the pentose phosphate pathway (PPP) to generate nucleotides and reducing potential in the form of NADPH. In this issue, Wang et al (2014) show that G6PD activity is post-translationally regulated by SIRT2, a cytoplasmic NAD+-dependent deacetylase, thereby linking NAD+ levels to DNA repair and oxidative defences, and identifying potential new approaches to treating this common genetic disease.

    http://onlinelibrary.wiley.com/doi/10.15252/embj.201488713/abstract

    As such NAD+ is needed to activate SIRT2 thus activating the PPP. Besides complex 1 oxidation of NADH to NAD+ and the G3P shuttle how else is NAD+ produced?
     
  3. Jack Kruse

    Jack Kruse Administrator

    Good.......youre making the correct links..........
     
  4. caroline

    caroline Moderator

    Hey! don't talk about me when I am at the ocean soaking up and taking in the stuff I understand!!

    besides ...... Yew and others here are our future - he can handle anything you throw at him by the look of things :D

    I hate to admit it ..... right now you probably couldn't even slow down enuf to wait for me .... but I do have other attributes :p

    I will do what I can .......taking in the big picture!

    not sexy or cool I guess .... but it is what it is.....and I do seem to be having a positive influence on others in my life.
    I will take that with a lot of gratitude .... and thanks for all you are doing.

    How does it feel to be a movie star?????
     
    Martin and Josh like this.
  5. Jack Kruse

    Jack Kruse Administrator

    Caroline........I do what I do to further the cause. I think when you see how they caught me off guard in filming you'll get it. Too much of a good thing can be wonderful. Helping others is my duty. They uncovered my weakness..........weakness makes us vulnerable; to make yourself vulnerable is to show your strength. Harry asked me about Kate.......she is proxy for all of you. In that instant I became small. You always have to be willing to be little to a larger story.............and they caught me off guard and on film with my response.
     
  6. Jack Kruse

    Jack Kruse Administrator

    Everyday you all and especially people like Kate teach me.........y'all don't realize it yet, but it is true..........I'm but an apprentice, in a craft where no one ever becomes a master.
     
    Josh likes this.
  7. caroline

    caroline Moderator

    I very clearly saw that in Orlando ..... sometimes I know more than you think ....but then again - you are a mere mortal - a mere man!

    I have told you this before .... I have always gotten it ..... I have always gotten you.

    I have a huge amount of respect for what you are doing and the man you have become ..... do I think you are perfect??? - heck no! You do show your vulnerability occasionally! You would be impossible otherwise! That is said with a huge amount of love ...and you already know that.
     
    Last edited: Dec 6, 2014
  8. ssj3

    ssj3 Silver

    Well right now I cant bring myself to sit down on this machine long enough to keep up with all the postings, blogs and make enough connections to ask good questions. And for someone who is usually all-in, it can get pretty frustrating when it starts to go 'right over my head'. I can only get through it these days if I print it and read while I am outside... and as with most things, put the effort and time-in = greatness/success/understanding.

    Shite... i've left the water on the asparagus!
     
    caroline likes this.
  9. caroline

    caroline Moderator

    You pretty much said it all Rob .......
    I can't even come up with a dumb question right now ..... so I will go to the beach instead! Lots of guys in speedos, lots of sun, lots of topless sunbathing .......
     
  10. yewwei.tan

    yewwei.tan Gold

    :rolleyes:

    Haha, we're all just pretending to know stuff that we don't, in hopes that daring to ask the question leads to the realisation of true answers. o_O. "Fake it till you make it" is alright so long as you're just trying to feed your own curiosity (and not trying to sell something).

    ----
    Hmm, now I need to think about G3P again. Two of Dr Kruse's posts come to mind ....

    ----

    'PPP and Glycogen' thread -- http://forum.jackkruse.com/index.php?threads/ppp-and-glycogen.9798/#post-111421

    The key is understanding the G3Pdh shuttle in out mitochondria is a major redox switch

    If you look in EE12 I posted a pic of the redox potentials from NADH to O2. Study it. It is critical. You guys all think life is based upon pathways in books that do not use the redox potential in that pic.

    http://jackkruse.com/energy-epigenetics-12-battery-charged/

    [​IMG]

    It appears that glycerol-3-Pdh is critcal protectant against electron and proton overload from any source in mitochondria. It protects us by inducing insulin resistance.

    When you have high blood sugars married with high exogenous insulin or fructose consumption from a bad diet to induce physiologic insulin resistance you need to have mitochondrial G3Pdh for effective reverse electron flow through complex I to generate mandatory superoxide/H2O2 for mitochondrial signaling.

    The interesting point is that mitochondrial G3Pdh inputs electrons to the CoEnQ couples in cytochromes for electron tunneling which has a redox potential of +20mV

    So with respect to mitochondrial G3Pdh, it is taking a cytoplasmic NADH, which could theoretically be shuttled to the mitochondrial matrix, and hence to complex I, at -280mV, and inputting it to the ETC at +20mV.

    The energy lost by skipping from -280mV to +20mV would normally pump four protons to generate heat.

    After a glucose load any oxidation of the abnormally elevated FFAs of insulin resistant people still provides a continuous +20mV input using ETF dehydrogenase's FADH2 acting on the CoQ couple, which is ultimately derived from the FADH2 of the first step of beta oxidation, ie it's FADH2 transporting electrons all the way, there is no energy wastage when using fats to limit insulin's action.

    In the absence of these inappropriate FFAs, the correct way to reduce the CoQ couple is using mtG3Pdh which shuts down insulin's action at the cost of generating heat because it uses NADH, stepped down to FADH2, as a direct input at the CoQ level.

    We want a reduced the CoQ couple when there is metabolic oversupply as a reduced CoQ couple allows reverse electron flow through complex I and insulin resistance. Insulin resistance, via reverse electron flow through complex I, is what is wanted, heat is a by-product.

    What if that elevated FFA level was maintained long term, say if you are eating a ketogenic template? As adipocytes become progressively more resistant to the the anti-lipolytic effect of insulin (another aspect not material now), plasma free fatty acids rise even under levels of insulin which should be suppressing them.

    Unless these free fatty acids are converted to CoA derivatives they will DIRECTLY uncouple respiration themselves. This should reduce delta psi while increase metabolic rate

    A reduced delta psi will not support reverse electron flow through complex I!!!!!! Here is where a lowered redox hurts. The essential insulin induced pulse of superoxide that is converted to H2O2, will not occur. Mitochondrial signaling is then BROKEN. There will be fasting insulin resistance. This paper spelled it out.http://www.ncbi.nlm.nih.gov/pubmed/23730255

    (*** Sidenote: How is this all linked to the action of superoxide dismutaste? ***)

    Equation for Complex One activity: http://en.wikipedia.org/wiki/NADH_dehydrogenase_(ubiquinone)

    NADH + H+ + CoQ + 4H+in → NAD+ + CoQH2 + 4H+out​

    Reversing it (as is the case in insulin resistance) produces extra protons and consumes both NAD+ and Ubiquinol (CoQH2), implying that electrons are consumed in the reaction.

    The reverse reaction seems to take place only when the membrane potential of the inner mitochondrial membrane is high (lots of electrons), and it feels to me as a way to specifically get rid of excess high powered electrons. Maybe that's why NAD+ absorbs strongly in the UV range ...

    ----

    'Low Carb/Insulin Resistance' thread -- http://forum.jackkruse.com/index.php?threads/low-carb-insulin-resistance.8934/page-6#post-102730

    This glycerol 3 phosphate molecule has a special shuttle. This is a metabolic pathway controlled by transition metal maxwell demons.

    It allows electrons to skip cytochrome 1.
    Using it allows cytoplasmic NADH to enter the electron transport chain.

    They happen to have two special glycerol 3 phosphate dehydrogenases which make up the shuttle.
    • Free in the cytosol there is cytosolic G3P dehydrogenase, which actually uses NADH to add a pair of hydrogens to a glycolysis intermediate (dihydroxyacetone phosphate) to form G3P directly.
    • The other G3P dehydrogenase really does dehydrogenate G3P, back to dihydroxyacetone phosphate.
    This second G3P dehydrogenase is embedded in the outer surface of the inner mitochondrial membrane. KEY POINT!!!

    Think what I told you special in the quantum electron blog 2 years ago about FADH2? And it contains an FAD/FADH2 moiety which takes these two hydrogens and uses them to reduce the CoQ couple, feeding electrons in to the electron transport chain.

    FADH2 is our special fat pathway quantum tunneler......it allows glucose to act like saturated fat when the shuttle is active in cold environments or during starvation.

    When the shuttle is working we pump electrons from cytosolic NADH directly in to the mitochondrial respiratory chain through the FADH2 tunneler. When you do this............it is electron only required and no pumping of protons. Anybody see WHY yet?​

    Nope, I don't see why yet :rolleyes:. But I assume that you don't pump protons because you don't need to pump protons.

    Random quote from wiki article on FADH2 (http://en.wikipedia.org/wiki/Flavin_adenine_dinucleotide):

    The primary biochemical role of FADH2 in eukaryotes is to carry high-energy electrons used for oxidative phosphorylation. Its hydrogens remain in the mitochondrial matrix, whilst FAD is tightly bound to a dehydrogenase enzyme
    Does this mean that proton concentration in the mitochondrial matrix does not change as a result? :confused: Fe-S clusters play into this as well, being the main electron carries for this FADH2 tunnel .... Again, I don't understand the science here enough, and more reading is required.

    (Sidenote: FADH2 is yet another adenine containing compound. See my quick note on adenine below)
     
  11. yewwei.tan

    yewwei.tan Gold

    Most info I see cites adenine as the responsible agent for the UV absorption peak of both NAD+ and NADH.

    However, none of the sources seem to say how absorption of UV light affects the shape of NAD+, and the resulting affects when bound to oxidoreductases.

    Oxidoreductases themselves are big structures of multiple parallel beta sheets (http://en.wikipedia.org/wiki/Beta_sheet), whereby sheets are linked by hydrogen bonds, and each sheet has alpha helices at the ends (http://en.wikipedia.org/wiki/Alpha_helix).

    My childish brain wants to think of these beta sheets as tightly packed ladders of hydrogen atoms just asking to be bounced around by all sorts of forces.

    Sidenote: I remember Jack mentioning Total Adenine nucleotides (TAN) before, and how they should rise through the day and be highest right before sleep, which I assume will recycle these during autophagic processes. Caffeine's proposed mechanism of action is by inhibiting adenosine receptors and keeps total adenine nucleotide levels down​

    NAD+ has a very unique shape:

    [​IMG]

    [​IMG]

    I would think it is very polar thanks to all the phosphate bound oxygen atoms (and a hanging electron on 2 oxygen atoms), but the 3D structure looks strangely symmetrical.

    Shape will be important when trying to answer the question of how exactly NAD+ activates other pathways like the sirtuin based pathways and the G3P shuttle. Why is this shape, which is relatively flat, and with nitrogens hanging at the edges and oxygen sitting closer to the center, and important configuration for cellular signalling?
     
    Paleodocteur likes this.
  12. I love how when i turn on the computer I see the same questions that where turning in my head, already on the forum….
    I was also wondering at which angle , which side would these waves rock this NADboat. 200 nm seems larger than the boat. It almost seems that the main bean/axis because of the M weight of PO4 would indeed be in the middle. the ribose making a floor plan. Adenine and nicotinamide the sails ( or the battery with their double bound )
    Nicotinamide receives the Rogue element ( from UVed EZ Water) at the top of the back sail > change in energy state in the N(+)unbalanced ring > change something in the (N loaded )Adenin or front P loading-ribose.
    Here is what I was toying with today. NightNights
     
    Da-mo likes this.
  13. zoomonNADPH.jpg
     
    Marie likes this.
  14. Josh

    Josh Gold

    After the EU Workshop, I took a sidetrack and read a couple of books that start with the concept of "shape/structure" as the fundamental in this universe. Some people seem to have called it "sacred geometry", yet the concepts seem fairly grounded in the reality of what is emerging....it is the same story I have encountered elsewhere...one must separate the wheat from the chaff...

    http://en.wikipedia.org/wiki/Flower_of_Life

    http://www.themeasuringsystemofthegods.com/The Secret The Flower of Life (vol.1).pdf

    https://www.google.com/url?sa=t&rct...tt2BUhwoENt5mJQxg&sig2=TzjQInmkCEtIrcEGpajb3w

    [​IMG]
     
    Da-mo likes this.
  15. ssj3

    ssj3 Silver

    Ok we have vibrations and oscillations... so say I am training and pounding away on my quads which are fully pumped with blood, does this 'stretching' create vibration/oscillation, with in-turn can create an electric field and subsequent magentic field??

    I was just thinking of this because of the upregulation of GLUT4 during training... and then came across some articles showing GLUT transporters responsible for cell DHA uptake (and something to do with reduction to Vitamin C within cell). But these are supposedly glucose dependent transporters.
     
  16. this is the basis of sinclairs work nowdays
     
  17. Da-mo

    Da-mo Gold

    It may be more the frequency or harmonic that it resonates with rather than the wavelength. Perhaps different multiples of wavelength or harmonic will have different effects. IIRC, the frequency found to destroy cancer cells was linked to the 11th harmonic in this TEDx at 8:32. Makes me wonder what effects the other harmonics have if any.
     
    Last edited: Dec 8, 2014
  18. Da-mo

    Da-mo Gold

    Found the following. Dont know if it will help you since I dont understand what you are discussing but it seems applicable somehow.
     
  19. Jack Kruse

    Jack Kruse Administrator

    ^^^^this is how they become entangled.........
     
  20. Jack Kruse

    Jack Kruse Administrator

    Yep. EE12-13 is key stuff for NAD+ and the link to the stuff in Tensegrity 5-11
     

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