CPC #27: THE CIRCADIAN MECHANISM AND NAD+

Your eye can be a clock or a camera. A blind man’s world is bounded by the limits of his touch and he relies on his timing; an ignorant man’s world by the limits of his wisdom; a successful man’s world by the limits of his vision and sense of timing. Man is the most complex eukaryote. Therefore he has the most sophisticated time piece in his eye that controls protein turnover. Protein turnover is a synonym for ubiquitin marking.
Eukaryotes spend 80% of their total energy budget on protein synthesis.That process is controlled by ubiquitination rates in cells. This is why you need to understand ubiquitin. Once you master ubiquitin you can use that recovered energy to reverse illnesses. Each peptide bond requires 5 ATP to seal the bond. That amount is 5 times as much that is needed to polymerize nucleotides into DNA!! Each protein is reproduced in thousands of copies, which are continuously turned over by ubiquitin to repair wear and tear. Elevations of ubiquitin marking are usually associated with higher blood glucose and ammonia levels.  This occurs because of damage in the urea and TCA cycles at Kreb’s bicycle.  Cell become unable to use beta-oxidation and protein cycles for biosynthesis.  Too many people are now blaming sugar and glutamine in cancer cases when it is clear the mitochondrial damage is making cancers have to use glycolysis and the PPP exclusively for bio-synthesis because of mitochondrial damage.  Cancer is a circadian disease in my opinion.

 

 

Medicine today treats the eye as a camera almost exclusively, when its most important physiologic role is as an optical clock. It turns out cataract formation and glaucoma are the best evidence that the timepiece in your eye is no longer working in concert with your gut, skin, or any of your cells properly. I believe all tissues contain time crystals that go awry because of a lack of sunlight during the day and a lack of darkness at night. When this occurs diseases usually follow.

 

 

 

Breast cancer patient usually has very abnormally low Vitamin D and melatonin levels when they are sampled. They rarely are because conventional oncologist DO NOT believe cancer is a circadian disease caused by mitochondrial dysfunction in the mitochondrial matrix. They also do not understand how glucose fits into this story. Most people today view elevated blood glucose as a pathologic condition related to a Warburg metabolism. That is another big error. When the clock in your eye is altered there is downstream collateral disarray in the peripheral clock genes. There is now another way to perceive an elevated blood glucose as a clinical sign of elevated ubiquitin ratios in all proteins because of a dysfunctional TCA and urea cycle.

 

 

Glucose is fully capable of braking ubiquitin cycling when ubiquitin is coupled to the cell cycle by normal solar light cycles as the picture above shows, but not when it is uncoupled and isolated due to altered solar cycles. The reason glucose has this ability because it contains a strong blue light signal in it for the SCN in the eye to provide negative feedback for the SCN. This ability is lost when light cycles are uncoupled from the nitrogen cycle in the eye or gut. When it is isolated, glucose levels go through the roof BY DESIGN to stop the PER 1 and PER 2 clock genes from turning over proteins by ubiquitin marking in cells. I believe eventually the narrative that cancer feeds on glucose will die a fiery death under the weight of new data about the PER gene products.  PROTEIN Turnover is the most energy costly activity a living thing does.

Most view the eye as a camera, but some of us see it as a optical lattice clock first.  HYPERLINK

In my recent webinar series for members on my site, (March through June 2015) I taught you about how the loss of negative feedback control in coupled biologic systems is the sentinel event for aging and disease generation. Moreover, I showed you what happens when you lose it on one side of the coupled event. There I used predator or prey to make the point. If you alter the balance of predator or prey the result is always the EXTINCTION of both animals. I have told you that in aging and neolithic disease generation that NAD+becomes altered in relation to NADH. This occurs because of defects in the TCA and urea cycles where the hydrogen is recycled from metabolic substrates to the electron carriers used in glucose metabolism at cytochrome 1.

The chronic loss of NAD+is the critical sign of a loss of negative feedback control of the ubiquitin cycle. This data scales directly to our molecular circadian clock and our peripheral clock genes (CCG’s). The LCHF cancer researchers are way off on their beliefs about the demonization of glucose in most cancers.  This same relationship also exists between the two coupled systems that control the eye clock protein timing mechanisms. When these proteins are drowned in blue light, it changes the molecular resonance coupling and this causes the extinction of the gears that control your timing mechanism in every system in your body. This is why blue light is associated with just about every neolithic disease known to man.  Where it occurs first is where diseases manifest soonest.

 

 

The current model of the mammalian circadian clock includes two interlocking transcription-translation feedback loops comprised of several so-called “clock” genes and their protein products, which ultimately regulate the transcription of “clock-controlled” genes. These feedback loops consist of positive and negative components. The positive components include the basic helix-loop-helix-PAS domain transcription factors, CLOCK, and BMAL1. These transcription factors heterodimerize, translocate from the cytosol to the nucleus, and bind to circadian E-box promoter elements that enhance the transcription of genes encoding the negative components PERIOD 1 & 2and CRYPTOCHROME 1 & 2.

This month in May 2018:  It appears my educated guess about PER1 and PER 2 in breast cancer was spot on.  Read this hyperlink.

The CRYPTOCHROME and PERIOD proteins feedback inhibit the transcription of the Cryptochrome and Period genes by blocking CLOCK/BMAL1-mediated trans-activation. The second feedback loop involves the trans-activation of the Rev-Erbα and Rora genes by CLOCK/BMAL1. The protein products of these genes compete for binding to RRE elements in the Bmal1 promoter, driving a daily rhythm of Bmal1 transcription and closing the second feedback loop. Rhythmic expression of these clock gene products produces circadian clock outputs by regulating transcription of clock-controlled genes (CCGs). At least some of these CCGs, including aanat, the gene encoding the penultimate enzyme in the melatonin biosynthetic pathway, contain circadian E boxes, which have a core nucleotide sequence of CACGTG and are activated rhythmically by CLOCK/BMAL1. Post-translational regulation, including phosphorylation, acetylation, ubiquitination, sumoylation and proteasomal degradation is also important in the regulatory mechanisms generating the circadian oscillation. All of these coupled processes become unhinged from light signaling to affect nitrogen, water, and carbon flows in cells to cause many neolithic diseases because of mitochondrial dysfunction.

 

 

SUMMARY:

Once your SCN timing mechanism goes haywire it is a matter of time before your circadian clock genes in tissues the SCN controls also goes haywire and result in diseases. What will be the ultimate result? EXTINCTION of both sides of the circadian timing mechanism and cancer is the ultimate result. Mitochondrial are self-regulated by just programs in humans.  Those programs are autophagy and apoptosis.  Melatonin helps augment autophagy by repairing mtDNA and acting as an antioxidant in darkness.  Interestingly enough, it is made first in the eye by an aromatic amino acid by sunlight.  Apoptosis is controlled by UV-A light because it releases nitric oxide which inhibits ECT at cytochrome 4 to increase cell suicide.  Cancer cannot exist with intact apoptosis.  This makes me believe sunlight is the ultimate vaccine for cancer.  The key is your skin and eye have to sense the full spectrum of the sun’s light to get the benefit.   It should be interesting to you that plants do not get cancer in nature. There is a deep reason for this that will be covered in this series. Cataracts, glaucoma, and many autoimmune conditions are earlier appearing neolithic diseases that often predate oncogenesis because of an elevated ubiquitin rate which is a MARKER for matrix dysfunction that cause abnormalities in NAD+.

CITES:
1. Herzog ED. Neurons and networks in daily rhythms. Nat Rev Neurosci. 2007;8:790–802.
2. Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, et al. Resetting central and peripheral circadian oscillators in transgenic rats. Science. 2000;288:682–685.
3. Ko CH, Takahashi JC. Molecular components of the mammalian circadian clock. Hum Mol Genet. 2006;2:R271–277.
4. Munoz E, Baler R. The circadian E-box: when perfect is not good enough. Chronobiol Int. 2003;20:371–88.
5. Gatfield D, Schibler U. Proteasomes keep the circadian clock ticking. Science. 2007;316:1135–1136.

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508210/

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