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Pyst Protein subverts the warburg effect, an essential component in pervasive disease.

Updated: Sep 18

This article will be more intricately edited in the future. This article provides useful content for patients, practitioners, researchers, administrators, organizations requiring rapid concise information about all versions of oncology, disease, diminished outcomes, and solutions that can be rapidly integrated into decisions, care, programs, and social constructs.

The website and foundational document set exhibits Pyst Protein and its ability to separate DBC1 from P53 preventing each other from producing coordinated cascade of diminished biological function when any one of these factors has become impaired. P53 is expressed when PEMT is downregulated, implementing strong regulatory influence in numerous pathways, enabling massive apoptosis among cellular entities and preventing particular cellular entities from experiencing apoptosis. Among these are P53 regulation of glucose endocytosis by downregulating GLUT, P53 regulation of energy molecule mining by downregulating Glucose 6 phosphate dehydrogenase to diminish pentose phosphate pathway synthesis of nucleotides and downregulating glycolysis production of energy molecules from 32 to 6 per cycle, both known as anaerobic glycolysis. Essential to this anaerobic glycolysis is downregulation of PEMT integration CH3 with its hydride into phosphatidylcholine to produced enriched phosphatidyl1methylethanolmaine/2methylethanolamine/choline, each being strong organic/inorganic phase separators, inorganic/organic phase transfer agents, antihistamines, structural deteriorator of oncological potentiating molecules, potentiators of super clot buster tissue plasminogen activator, and serine proteases to promote embryonic plasticity.

The important understanding of the warburg effect is that when PEMT is downregulated, hydride as CH3 is being inadequately packed into membrane phospholipids, disrupted the quantum, angular, spooky dynamics that enable optimal biological function and plasticity, while the resultant freeing of hydride from membrane integration and freeing of choline from being integrated into acetylcholine for storage, both are replaced by freed choline for integration ATP by the cdp-choline pathway to provide phosphocholine upregulation used by pervasive disease and nonresolution phase survival signaling through 26s/20s/19s proteosome upregulation, S1P upregulation, GSK3 upregulation, S1P receptor upregulation and GCPR upregulation. This syndrome involves methylene bridge cysteine upregulation, BCL2 upregulation, and other factors which promote mitochondrial potential impairment with Parkin accumulating in the outer membrane, mitochondrial fission, and disruption of the Mitochondrial Associated Membrane through which the endoplasmic reticulum supplies phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine and Ca2+ to the hundreds of mitochondria that can be in each cellular entity. P53 downregulates Glycolysis and Pentose Phosphate pathways, as well as regulates cellular survival outcomes to prevent dysregulation of genome and physiology.

Aerobic glycolysis emerges when P53 becomes impaired in its regulatory potential and pathways, resulting in too much energy being freed for utilization by antiplasticity pathways such as upregulated cdp-choline pathways and when too much energy is mined from membranes and tissues without PEMT replenishing membrane phospholipid hydridic density and CH3 density. PEMT2, in particular, emerges near gestation and performs as a regulator of development by performing in the mitochondria and performing in membranes shared by mitochondria and endoplasmic reticulum subcompartments. PEMT2 in mitochondria, but PEMT1/2/3 each increase the ratio of CH3 to catalytic molecules and ratio of CH3 to expanding structural lattices to which CH3 attaches to abates expansion or development.

Thus, the canonical models of disease include increased energy availability through aerobic glycolysis and upregulated cdp-choline pathway through choline kinase alpha attachment of ATP to free choline, each along with continued downregulation of PEMT and potentially with continued upregulation of P53 and P53 impaired function The canonical model of disease includes continued downregulation of P53, impaired availability or impaired function of P53, along with upregulation of Glycolysis and upregulation of the CDP-Choline pathway's attachment of ATP to Choline by choline kinase alpha. The secondary aspect of canonical models of disease are diminished density of CH3 and Phospholipids, along with diminished exhibition of fatty acids characteristic of PEMT catalysis including DHA, EPA, oleoylate, extended length arachidonic acid, palmitate first fatty acid in fatty acid beta oxidation, and ether linked membrane insulating fatty acids. This also affect LPCAT/MBOAT fatty acid shuffling of diverse fatty acid in the Lands cycle where phospholipids and fatty acids are free by phospholipases and phosphodiesterase to be integrated into phospholipids again by integrating lysophosphatidylcholine with free fatty acids. These are disruptive of plasticity because phase progression of emerging substructure add superstructure in lipid chemistry dynamics are affected by fatty acid distribution, phospholipid ratios and other factors.

Choline exhibits 3 methyl groups and thus at least 3 molecules of hydride or 3 loci of hydridic character, although hydridic character is canonically considered to be distributed within a molecule. Hydride can be freed, distributed or applied incompletely from a hydric context to another molecule or center. Carbocation rearrangements can occur within a molecule, between a compound molecule or between disconnect molecules.

Choline can be imported, produced de novo by PEMT catalysis, freed from membrane phospholipids by phospholipases and phosphodiesterases, and synthesize and oxidized by the bidirectional choline oxidation pathway. Intricate review of the literature in this compendium of resource found multiple contexts of potential noncanonical freeing or synthesis of choline. This includes potential derivation of choline from Super Hydride which require only substitution of nitrogen for the central atom. Numerous other molecules such as caffeine are structural homologues of choline, but these seem to be regarded as noncanonical potentialities. Super hydride is involved with eluting of hydride from the universes level hydride zero-point field or universes level aether of hydridic fields which vary in density, location and status.

The cdp-ethanolamine pathway involves integration of new CH2 or methylene brides into metabolism and physiology by converting ethanolamine to ethanolamine to citidylylethanolamine to phosphatidylethanolamine, followed by phosphatidylethanolamine and Fatty Acid Synthesis integrating at the function of PEMT which moves CH3 from s-adenosyl methionine int three sequential transferase catalytic actions to the nitrogen of phosphatidylethanolamine, resulting in de novo synthesis of enriched, resolution phase dense, hydride dense phosphatidylethanolamine. This pathway, the cdp-ethanolamine pathway, PEMT intermediate substrates PMME, PDME and phosphatidylcholine, along with THMT product methylthioglycolic acid, are toxic, caustic and in the instance of choline are caustic quaternary ammonium factors, performing as extreme antihistamines, separators of biotic phase from abiotic phase, and are sequestering of useful factors from the abiotic phase for movement into the biotic phases. Essentially, these factors melt plastics that have integrated into tissues, deteriorate the structural bases of diverse toxins, xenobiotics, and oncology potentiating molecules. These behemoths, titans, at the center of physiology that sequester space in the biome for biology and Life to emerge, persist and become sustained. These factors are consistently commandeering the biome and the Universes to the benefit of biology, Life and vital being.

Choline is a cation, or negatively polarized alkalinity promoting factor, and in its multiple isoforms are water-soluble quaternary ammonium. Choline hydroxide is an isoform that is a choline base, presenting its function in redox and ph system function. This presents another mechanism through which choline functions to promote an alkaline background ph within 7.2. to 7.6, particularly ph within 7.35 to 7.45 and specifically ph of 7.4.

Choline attracts water molecules which cause a typical exhibition of choline as a clear hydrated, viscous fluid that has an odor similar to trimethylamine because aqueous solution of choline gradually move from stability to dissociation into glycol, trimethylamine and polyethylene glycol. These explain why choline dense foods promote trimethylamine in digestive pathways which can be translated into trimethylaminenoxide by microflora or can transit digestive pathways in leaky gut syndrome to become reduced by Flavin monooxygenases into trimethylaminenoxide. Odorous trimethylamine from upregulating trimethylamine is known as trimethylaminuria and is an ICD classified condition. Preventing trimethylaminenoxide is performed by TMA lyase inhibitors, 33DMB, fasting, avoiding meat/chicken/eggs/fish unless accompanied by or in context of supplemented olive oil, grapeseed oil, balsamic vinegar, regular laxative instrumentation, postbiotics, prebiotics, probiotics or steady obtainment of macrobiotic foods.

The choline observed in supplementation can typically be produced by exposing choline to 2-chloroethanol derivable from ethylene oxides, while hydrolysis of lecithin can be a way of deriving choline from natural substrates, and while lecithin is group of mixed emulsified molecules which occur in biological material and comprise vast aspects of physiological structure in a way the involves phase transitions in lipid chemistry to produce microstructure and superstructure. Lecithin is important to biology and can be transformational as a nutritional, supplemental and therapeutic vectors because it supplies the factors that comprise the substrates for and constitutes molecules pervasively exhibited in biology and biological structures.

Phospholipids are important because the attract water, attract fatty substances, and be inverted to produce polar and nonpolar extremities resulting liposomes, cellular enclosures and the bilipid membranes essential to eukaryotes.

Importantly, lecithin’s constitutive factors exhibit different polarity, which enable these to participate not only circulating systems management of pH but when aggregated in dense cellular membranes, exude polarity into the environment. These promote the background polarity characteristics that result in biology enabling disequilibrium and gradients. Shuttling of phospholipids through the lands cycle involves shuffling fatty acids, freeing phosphatides including production of lysophosphatidylcholine, application freed enriched fatty acids to deteriorate nonresolution phases, promote resolutions phases and stability, followed by integration of lysophospholipid with shuffled fatty acids to produce the diverse microstructure and superstructure exhibited in organisms of different species and organisms of the same species.

Lecithin includes Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, and choline, while lecithin can occur in different viscosity, density, and characteristic emulsifications, while balances between phospholipids can also exhibit variation. Lecithin in aqueous solution exhibit diversity characteristics of biology including phospholipid configurations of bilayer sheets, micelles, lamellar structure, liposomes, surfactant characteristics and amphipathic characteristics.

Lecithin was discovered most incipiently in about the middle 1700s or earlier.

Choline in the canonical unidirectional pathway includes choline and ATP becoming phosphocholine and ADP, requiring free choline or metabolite of choline, phosphocholine and CTP becoming cdp-choline and pyrophosphate, cdp-choline and DAG becoming phosphatidylcholine and CMP. Choline oxidation occurs in the mitochondria and thus when mitochondria become impaired or deteriorated, this nonPEMT pathway for phosphatidylcholine synthesis becomes deteriorated, resulting in this foundational use of recycled choline and methylene bridge conversion to phosphatidylcholine become diminished. This explains in more intricate detail why PEMT2, mitochondrial PEMT2 is abrogated in pervasive advanced phase of disease, including a massive deterioration of not only enhanced plasticity PEMT2 synthesized phosphatidylcholine at the conclusion of the cdp-ethanolamine pathway but also including deterioration of phosphatidylcholine synthesis through the cdp-choline pathway.

Importantly, there are at least two pathways for supply of phosphatidylethanolamine, including cdp-ethanolamine pathway and through phosphatidylserine decarboxylation/carboxylation cycling that occurs from exhibition of phosphatidylcholine and processing of phosphatidylcholine toward multiple outcomes, including phosphatidylcholine and ceramide becoming sphingomyelin and sn-1,2 diacylglycerols integration competent for sn-1/sn-2 positions in phospholipids.

Phosphatidylserine may be synthesized from phosphatidylethanolamine and serine bp PSS2 resulting in ethanolamine and phosphatidylserine. Phosphatidylserine may be synthesized from phosphatidylcholine and serine, resulting in choline and phosphatidylserine. These present another pathway for recycled choline exhibition, recycled ethanolamine exhibition, and synthesis of de novo phosphatidylserine.

The cdp-choline pathway and the cdp-ethanolamine pathway can potentiate phosphatidylserine, but the cdp-choline pathway produces choline which can enter the choline oxidation/cdp-choline pathway.

Although PEMT2 deterioration is correlated with mitochondrial deterioration, a more pertinent observation is that PEMT2 deteriorated function is linked to dissociation of the mitochondrial associated membrane from connecting the endoplasmic reticulum to hundreds, potentially, of mitochondria, such that Ca2+, Phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol or other substrates cannot be supplied from the endoplasmic reticulum to mitochondria.

Phosphatidylserine can be recycled by phosphatidylserine decarboxylase to produce CO2 and phosphatidylethanolamine, presenting another mechanism through which ph is affected by phospholipid cycling.

Phosphatidylethanolamine from phosphatidylserine and phosphatidylethanolamine from the cdp-ethanolamine pathway exhibit different distribution of fatty acyl species among the sn-1 and sn-2 positions. Experimental small nonhuman mammalian contexts exhibit phosphatidylserine potentiation of primarily polyunsaturated fatty acyl species at sn-2, while the cdp-ethanolamine pathway exhibits preferred exhibition of monounsaturated fatty acids or 2-unsaturated fatty acid species at the SN-2 position.

Newly synthesized phosphatidylserine species were observed in this small nonhuman mammalian experimental context to emerge in the mitochondria followed by dispersion into equilibria between mitochondria and endoplasmic reticulum. This suggests that mitochondrial deterioration which promotes dissociation of the mitochondrial associated membrane prevents newly synthesized phosphatidylethanolamine from being adequately or directly distributed to the endoplasmic reticulum. Downregulation of PEMT, then, may potentiate impaired exchange of phosphatidylethanolamine bidirectionally between the endoplasmic reticulum and mitochondria, while also potentiated in such conditions is impaired supply of products from cdp-ethanolamine pathway from mitochondria to endoplasmic reticulum.

Phosphatidylserine decarboxylase function may be essential for mitochondria because it enables synthesis of newly produced phosphatidylethanolamine. A review of serine metabolism suggests that serine can contribute new methylene bridge to products produced from it as substrate. The Phosphatidylserine synthase pathway, then, along with phosphatidylserine decarboxylase, may contribute new methylene to phosphatidylethanolamine pathway, performing as another modality of integrating new, unrecycled, undeteriorated methylene bridge into phospholipid cycling.

The literature places the antihistamine correlated cdp-ethanolamine pathway and its production of newly synthesized phosphatidylethanolamine in the endoplasmic reticulum, such that during impaired mitochondrial conditions, the newly produced ethanolamine cannot reach PEMT in the mitochondria. PEMT2 emerges near birth as a regulator of growth, while PEMT1 is a growth and development enabler exhibited since conception when PEMT function and the cdp-ethanolamine are assisted by downregulation of numerous competing pathways. The impairment of mitochondria produces exhibition of cdp-ethanolamine antihistamine pathway which promotes cleaning of the environment while impaired mitochondria also perform this activity to the benefit of version of PEMT this not a regulator of growth. This characterizes, not only a potential for unregulated growth but also explains the reprogramming of cellular entities toward immortal phenotypes during parthanatos and increasingly so when PEMT2 function becomes deteriorated correlatively to increasingly impaired mitochondrial function.

Anaerobic glycolysis is a syndrome that impose a systematic, increasingly detrimental and increasingly burdensome requirements on systemic buffering mechanisms and on mitochondria, in a way that is similar in producing increasing isolation of such components, increasing potential for deteriorated function and increasing susceptibility to disease. Aerobic glycolysis with the protection of the regulatory capabilities of PEMT2 seem to promote the most optimal physiological conditions even is only regularly sustained instead of being always enabled.

Information) “The Synthesis of Methyl Groups from Serine.” J Am Chem Soc. Volume 73. Number 11. Page 5509 to 5510.

Information) “Phosphatidylethanolamine Homoeostasis rebalanced through Mitochondria-Endoplasmic Reticulum Exchange.” Volume 16. Number 10. October 2020.

Information) “The CDP-Ethanolamine Pathway and Phosphatidylserine Decarboxylation Generate Different Phosphatidylethanolamine Molecular Species.” Volume 282. Number 39. Pages 28362 to 28372.

Deterioration of mitochondrial function and correlated deterioration of PEMT2 function, result in deterioration of the cdp-choline pathway which occurs in mitochondria.

Hepatic oxidation of choline can occur with import of choline from cytoplasm to the mitochondria, where choline dehydrogenase catalysis synthesis of H+ and betaine aldehyde, followed by betaine aldehyde and NAD processing by betaine aldehyde dehydrogenase into NADH and Betaine, while the literature in some instances suggests that this pathway can be inverted by thermodynamics and increased NADH compared to NAD. BHMT and methylene bridge cysteine can catalyze translation of betaine into 2methylglycine and methionine, followed by 2methylglycine/THF/FAD translation into sarcosine/5methyltetrahydrofolate/FADH2 by 2methylglycine dehydrogenase. Sarcosine, tetrahydrofolate and FAD can become glycine, 5-methyltetrahydrofolate, and FADH2 through catalysis by Sarcosine dehydrogenase. Glycine, tetrahydrofolate, and FAD can then become CO2, NH3, 5-methyltetrahydrofolate and NADH through catalysis of the glycine segmentation system which includes FAD and lipoate.

Glycine betaine, betaine, n,n,n, glycine betaine or trimethylglycine is an osmolyte regulation molecule which stabilizes the quaternary structure of proteins and enzymes to prevent pressurization or hydrostatic change, thermodynamic change and other challenging conditions from deteriorating, changing, impairment or permanently impairment enzymes and proteins.

Trimethylaminenoxide is utilized by aquatic organisms to stabilize proteins, enzymes and systems and changing depths, which is why its exhibition potentiates changes in vascular pressure and flow, requiring proactive and persistent management. The risks linked to trimethylamine oxide suggests that meat, chicken, eggs and fish usage as nutritional factors was a social and conscious adaptation to nutritional inadequacy in the environment and the P53 enabled shunting of glucose into actively exercising muscle tissue redirected focused development of the cerebral cortex and conscious capacitance toward immediate required focus on obtaining more sparsely accessible, more complicated access conditions and more choline nutrient dense sources of nutrition.

Information) Nutrient Metabolism. ISBN 978-0-12-387784-0.

Ancillary canonical nuance of disease also include decreased phospholipid, hydride and CH3 density in cellular entity membranes, decrease in the number of cellular entities per micrometer of tissue, and e merging of iNOS expression in cellular entities which are paused during hypertrophic phases from diminished PEMT de novo synthesis of choline in order to assure enough turgor to prevent cellular entities and tissues from collapsing from the density of anatomical mass. iNOS/NOS2 is essential in almost every very advanced disease, condition or diminished status, while PEMT is typically obliterated in its structure, function, of genomic translation/transactivation in advanced disease.

A recent study found that Iodide and Sodium were diagnosed as being deficient in nearly 90 percent of oncology diagnoses while the 10 percent excluded from such diagnoses had the potential of developing iodide deficiency and sodium deficiency in the 1 year and 6 months during which the group was subjected to assay of statuses of these metabolites. Importantly, both Iodide and choline are sodium coupled when imported by their respective symporters, such that these may compete for sodium to enable endocytosis. Also, in the intracellular environment, if choline is imported during PEMT inhibition, the result can be increase in supply of free choline for attachment of ATP and supply of choline kinase alpha which substrate to produce phosphocholine which is pervasively used in nonresolution phases, pathology. general and pathology promoting microbes. Phosphocholine is also an enabler of low-level nonresolution phase signaling, activation of platelets and activation of complements immunological system.

However, functional PEMT enables choline to enter into methyltransferase cycling and participate in enhanced biological stability, including massive detoxification, antihistamine, histamine, xenobiotic, PEMT and biosynthetic pathways. Choline has been mistakenly linked to oncology because cellular entities import more choline because PEMT is diminished in its synthesis of choline during conditions correlated with oncology. Pervasively, studies in which choline obtainment has been linked with oncology result in observation that after diagnosis, choline is inversely correlated disease. Iodine is also utilized to sustain membrane, glands and encompassing structures of endothelium and luminal areas.

DBC1, thus, integrates with SIRT1 to free NAD+/NADH, promoting cellular division, while dn-DBC1 is not able to integrate with SIRT and results in NAD+/NADH becoming integrated into SIRT1. The ability of DBC1 bring P53 along with its catalytic patterns is disrupted by Pyst and results in specific apoptosis among diseased tissue and oncology tissue, including monocytes. Thus, Pyst specifically counteracts cellular entities with reasonable levels of warburg effect or aerobic glycolysis.

DBC1 downregulation impairs the ability of P53 to activate PUMA and activate Bax, both of which are activators of apoptosis, explaining why DBC1 interaction with P53 is important in cellular outcome decisions. Pyst, then must prevent PUMA and Bax activation, resulting in another mechanism of cellular deterioration. Pyst upregulates apoptosis through UNC5B upregulation and does not require P53 to invoke this apoptosis potentiating pathway. The characteristic mitotic phase pause induced by Pyst is correlated with increases in UNC5b toward increasing potential for apoptosis that is also correlated with UNC5b upregulated transcriptional activation and UNC5b posttranslational stabilization to prevent ubiquitylation and prevent proteolysis of UNC5b. PP2a is regarded as essential to UNC5b imposition of apoptosis while metrin-1 counteracts UNC5b promoting of apoptosis in Pyst expressing cellular entities in a way the results in metrin-1 being a promoter of cellular survival in Pyst expressing cellular entities.

Pyst, thus imputes a system that controls cellular outcomes correlated with UNC5b, metrin-2 and PP2a levels, while UNC5b, metrin-2 anPP2a are all presented as being downregulated in some oncology or oncology in a general sense.

Information) "UNC5b" J Virol. Volume 94. Number 14. 7th Month, 2030.

DBC1 enables P53 to activate PUMA and activate Bax. Bax and Bak are primary apoptosis inducing factors and are counteracted by BCL2 which is a survival enabling factor that counteracts Bax and Bak in a way that enables balance between these factors to determine apoptosis or survival of a cellular entity.

Downregulating DBC1 impairs P53 ability to activate puma and impairs the ability of P53 to activated Bax, resulting in increase of the BCL2 levels compared to Bax levels in promotion of cellular survival while also resulting in diminished ability of puma to cause apoptosis.

DBC1 availability displaces NAD and hydride carriers from SIRT1 and SIRT2, such that SIRT1 and SIRT2 have diminished deacetylase activity. SIRT1 represses P53 transcription and activation, or, simply, represses P53 transactivation.

DBC1 counteracts and diminishes the ability of SIRT1 and SIRT2 to repress transcription and activation of P53. Downregulating DBC1 using siRNA to prevent transcription of DBC1 before it can be post transcriptionally modified or posttranslationally modified, diminishes the ability of P53 to effect its regulation pathways and diminishes the ability of p53 to cause apoptosis, particularly through preventing transcriptional activation of puma and bax.

SIRT1 levels increasingly above 2.78 ng/mL is linked with pathology, renal impairment and increased diminished statuses linked to aging. alphaKlotho below 756.6 pg/mL is correlated with renal disease requiring hemodialysis while advanced phase renal disease can cause alphaklotho to become 50 percent lower than 756.6 pg/mL. SIRT1 and alphaklotho levels are linked to diminished outcomes correlated with aging.

Sirt1 is physiologically general while sirt2 is correlated with brain tissues. Sirt1 represses P53 enabled neurodegeneration by downregulating P53, puma and bax. Sirt1 one also represses FOXO pioneering development and regenerative pathway apoptosis programs. Sirt1 is considered to prevent cellular pathology from alzheimer’s, parkinson’s, and other similar conditions. Amyloid beta protein impairs the ampk/sirt1/pgc-1a pathway. Sirt1 overexpression hyperactivates alpha-secretases segmentation of APP amyloid precursor protein to hypercounteract central neuronal system pathology linked to alzheimer’s disease. Sirt1 activation also diminishes NF kB signaling and diminished microglial amyloid beta toxicity. Sirt2 is similarly protective in microglial neurodegeneration through NF kB downregulation, protective from olfactory neuron deterioration, and regulates insulin/igf-1 signaling in the neuronal cytoskeleton.

Sirt2 is expressed in cytoplasmic neurites and growth cones of postmitotic cellular entities. Impaired autophagy is linked with alzheimer’s disease and numerous other diseases including oncology. Sirt2 is a tubulin deacetylase that downregulates autophagy by causing microtubule disassembly, such that sirt2 downregulation enables microtubule assembly, enables cellular microtubule reestablishment, axonal transport, fusion of autophagic vacuoles to lysosomes, although phosphatidylinositol signaling is essential for autophagy vacuole budding and attachment, phosphatidylethanolamine can be assistive to autophagy, downregulation of bag1 attachment to hsp70 protein promotes autophagy, upregulation of bag3 protein attachment to hsp70 protein promotes autophagy, disruption or inhibition of the 26s/20s/19s proteosomes promotes autophagy.

Autophagy removes proteins and molecules from intracellular environment using tagging such as polyubiquitylation and other modalities that attach autophagic promoting catalysts to intracellular substrate for directing toward and into autophagic vacuoles for removal. Phospholipase D can enable lysosome budding from cellular membranes. Ratio of Phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine, all can determine cellular membrane and lysosome curvature and lysosomal ph. Likewise, phospholipid cycling can strongly affect ph of the microenvironment, particularly near membranes.

Sirt1 is conserved to mammals from other kingdoms and other genus or species, and in such other organisms sirt1 upregulation extends duration of being by as much as 70% or more. SIRT 1/2/3/4/5/6/7, sir and hst, all are categorized within the 4 classification categories of sirtuins, with all four classes being represented in mammals but not all class members being represented in all mammals. Mammalian sirtuins are somewhat complex and differ from other sirtuin function because Mammalian sirtuins are shuttled between the cytoplasm and nucleus with subcellular location being a component of differentiated function.

Importantly, deacetylation among sirt includes sirt1 generally in tissue, sirt2 in brain, sirt3/4/5 in the mitochondria to modulate atp availability, metabolism, intracellular signaling and metabolism with sirt3 shuttling between nucleus and mitochondria in response to cellular stress, and along with sirt6 being a nucleus factor translocatable to endoplasmic reticulum for potential deacetylation of tnf-alpha. Sirt7 performs its activities in the regions of DNA which encode synthesis of nucleolus which is a spherical structure produced during mitotic interphase which performs synthesis of ribosomes.

Sirtuins, importantly, may have some level of P53 interaction otherwise, although P53 is upregulated substantially when PEMT is downregulated or when injury, disease or impairment is exhibited at the tissue or cellular level. Sirt1 represses P53 enabled neurodegeneration by downregulating P53, puma and bax. Thus, when PEMT is functional, the role of sirtuins can be downregulated, particularly for airt1 and airt2. This strongly confirms the role of PEMT in downregulating levels of methylene bridge cysteine, and downregulating levels of methylene bridge cysteine that is not produced from PEMT catalysis because PEMT catalyzed methylene bridge cysteine is not considered to be detrimental. This strongly confirms PEMT as an antiaging factor in preventing methylene bridge cysteine upregulation which requires acetylation to counteract apoptosis inducing factor, counteract methylene bridge cysteine, and conserve sirt1, sirt2 and other sirtuin resources for activity other than countering P53 promoting of apoptosis.

Information) “Sirtuins and Their Biological Relevance in Aging and ‘disease linked to Aging’.” Aging Dis. Volume 11. Number 4. Pages 927 to 945. 7th Month, 2020.

Correlatively, emergency medicine regards near 7.2 to 7.6 as range of pH, while this is specifically regarded as ph 7.35 to 7.45 in the clinical literature and ph 7.4.

The base excess referential concept is a clinical diagnostic that calculates circumstantial amount of acid, strong acid, which must be added to each liter of fully oxygenated hematopoietic fluid to assure ph of 7.40, while base deficit calculates the circumstantial amount of base, strong base, that must be added to each liter of fully oxygenated hematopoietic fluid to assure a ph of 7.4, both at thermodynamic levels of 37 Celsius and with pCO2 level of 40 mmHg.

The strong ion difference is referred to as the difference between the strong ions (Na+, K+, MG2+, and Ca2+) compared to the anions ( Cl-, lactate, and urate).

Downregulation of PEMT prevents de novo synthesis of choline, and prevents ethanolamine from providing phosphatidylethanolamine that has lightly glycosylated tails or unglycosylated tails, prevent phosphatidylethanolamine that harbors new methylene bridges that translate e-, current, hydride, or waves into polymerization potential and structure, all from being translated into and as phosphatidylcholine with fatty acids enriched in DHA, Omega-3, oleoylate, highly combustible palmitate that is the first fatty acid in beta oxidation, extended length arachidonic acid, and ether linked insulating fatty acids. Phosphatidylcholine decreases the temperature at which superconductance occurs and promotes more and more efficient electron and hydride flow. Membrane packing of methylene bridges, hydride sequestered within methylene bridges, has emerged as strong indicator of health status and is diminished in pervasive pathology and detrimental aspects of aging. This results in dysregulation of metabolism and physiological structure, resulting in an enhance amount of activity, destabilizing and a more focused reliance upon ion balances in circulation and intracellular environment to supplant the cellular membrane and tissue which would greatly assist in maintaining ph near 7.2 to 7.6, ph near 7.35 to 7.45, ph at 7.4 and the balances of ph exhibited between 2hydrogen phosphate and hydrogen phosphate in the intracellular environment as pKa 7.21, including also the balances between hydrogen carbonate ions and bicarbonate ions which are more specifically near 7.4. The diverse pathways that comprise buffering systems, redox potentials, redox potential intensity, all may have increased requirements and require increased activity to sustain physiological pKa and physiological ph when PEMT is not producing adequate levels of new membrane packed enriched phosphatidylcholine, while such systems may become diminished in other priorities including maintaining of their own tissues, structure and function otherwise. Ephemeral conditions in such regard may have been expected by physiology while sustained conditions in such regard may represent disease and detrimental nuance of aging, although focused prioritization and maintaining of PEMT, hydride availability, and stability through civilizations, care, nutrition and understanding by individuals and groups of how to implement such priority, may be strongly and sustainably able to produce stability.

Information) “Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis.” Curr Gerontol Geriatr Res. Volume 2012. 302875. 2012.

The literature clearly links pervasive pathology and aging with impaired PEMT function, upregulated P53 and subverting of the capabilities exhibited by PEMT in regulation of energy metabolism, structural stability and exhibition of hydride within structure in a way that causes intracellular and extracellular environment to exhibit extratypical quantum, angular and spooky characteristics in sustainment of physiology and being.

Some of the literature observes that anaerobic glycolysis is defined by redirecting of pyruvate toward lactate anion while aerobic glycolysis is defined by directing of pyruvate toward krebs cycle, although anaerobic glycolysis is most defined by P53 downregulation glucose-6-phosphate dehydrogenase, downregulation of GLUT endocytosis of glucose, and downregulated production of Acetyl-CoA from pyruvate which results in diminished supply of acetyl-CoA to choline acetyltransferase synthesis of acetylcholine along with diminished supply of Acetyl-CoA to the krebs cycle.

The precise definition of anaerobic glycolysis presented by warburg includes the directing of glucose to lactate instead of glucose being directed to CO2. This definition is relevant because glucose entry into glycolysis through glucose-6-phosphate dehydrogenase is followed by multiple potentialities including downregulating of glucose-6-phosphate dehydrogenase by P53 or nad+ inadequacy, pyruvate synthesis from glucose, directing of pyruvate toward many potentialities, directing of pyruvate toward lactate anion or directing of pyruvate toward Acetyl-CoA which results in CO2 synthesis also as a byproduct, while also Acetyl-CoA can then be directed toward choline acetyltransferase and the krebs cycle.

Diminished PEMT production of phosphatidylcholine downregulates packing of hydride into cellular membranes and diminishes the ability of hydride to support a background alkalinity of 7.4, resulting in systemic increase in the requirement of buffering systems to help sustain ph at 7.4.

Lactate is now considered to be a signaling molecule which can activate G coupled protein receptor 81 and monocarboxylic transporters. Neoplastic change, renal impairment, pulmonary conditions, cardiomyopathy, atherosclerosis, impairment and adverse cardiomyopathy, all are linked to warburg observations of increased lactate production. However, this compendium of research was able derivatize this complex of factors to PEMT downregulation and P53 upregulations or P53 upregulation from injury or impairment.

Lactate can be metabolized by tissues including hepatic tissues, redirected to pyruvate by lactate dehydrogenase, and even depleted by lactate oxidase which the literature does not widely regard in human tissues although some of the literature present lactate oxidase in lactate metabolisms without regarding it as being either excluded from Human physiology or being in the metabolome of microflora.

The literature observes that glycolysis is performed when hypoxia occurs and downregulates the tricarboxylic acid cycle, followed by prevention of pyruvate from entering the mitochondria for oxidative phosphorylation or electron transport pathway, and alternatively exhibiting directing of pyruvate to lactate by lactate dehydrogenase. However, the process of downregulated glycolysis from 32 molecules of energy factor synthesis to between 6 and 9 molecules known as anaerobic glycolysis occurs resultant of PEMT downregulation and P53 upregulation. Lactate dehydrogenase E1alpha subunit phosphorylation and NADH availability regulate Lactate dehydrogenase synthesis of lactate, although NAD+ and lactate also regulate synthesis of pyruvate from lactate dehydrogenase. Sirt3, Sirt7 and possibly sirt5 can also regulated lactate dehydrogenase through acetylation/deacetylation status.

Lactate may be among the primary supportive metabolites in proopiomelanocortin neurons. This suggests that lactate may be transported and obscured within alkalinity to provide a stable supply of energy metabolism substrate that is not mined by other phases of physiology.

Small nonhuman mammals in experimental conditions exhibit typical 1.1 to fasting 2.5 ration of lactate to glucose, except for brain tissues, although lactate is the major metabolite in pulmonary oncology and pancreatic oncology.

These contexts explain the redox buffer mechanism by which NAD+/NADH, NADP+/NADPH interact in enzyme exchange or redox interactions that integrate hydride into hydride carriers or frees hydride from hydride carriers in order to balance free eV-, free electron levels, moments of hydridic fluorescence and free hydride availability in order to sustain a ph of 7.2 to 76, specifically a ph between 7.35 to 7.45 and a specific ph of 7.4. Increased availability of NAD+ compared to NADH or increase levels of NADP+ compared to NADPH is correlated with oxidation conditions that result in higher rates of activate metabolic factors, increase in the rate and dispersion of aging processes, and potentiating of conditions linked to aging, while in a context of upregulated reduction in which lower levels of NADP+ compared NADPH or lower levels of NAD+ compared to NADH emerge, there electrons are accepted instead of being oxidized/freed, oxidative stress resolution factors are decreased, and glycolysis is downregulated.

Oxidation is the abdication of hydride or hydrogen in the context of redox, while reduction is the acceptance of hydride or hydrogen in the context of redox.

Cytoplasmic LDH and Mitochondrial EDC complex I are major interconversion pathways for NAD+/NADH, while there are some enzymes that directly interconvert NAD+ and NADH. Enzymes such as sirtuins regenerate NAD+ from nicotinamide using a base exchange reaction that can cause the sirtuin to abdicate its acetylation transaction ability, although arginine adjacent to the nicotinamide integration loci (sirtuin nicotinamide “c pocket”) can regulate or toggle sirtuin nicotinamide recycling compared to deacetylation activity.

NADH can increase compared to NAD+ when mitochondrial respiration is impaired or downregulated, while similar conditions can result in increased lactate compared to pyruvate, although these conditions occur in more pathways than only translation between NADH/Pyruvate and NAD+/Lactate by lactate dehydrogenase, although these conditions can also be assisted or resolved by more pathways than only lactate dehydrogenase.

Lactate oxidase translates lactate into H2O2, but like superoxide dismutase translation of superoxide to H2O2, catalase or other antioxidants can metabolize H2O2 and promote translation extracellular lactate into pyruvate. However, catalase is susceptible to deactivation by methylene bridge cysteine in a way that presents the affect of methylene bridge cysteine to numerous redox enzymes and pathways, such that methylene bridge cysteine constitutively and through its activity or effect to atom level oxidation status or molecular level oxidation status, can be promoted to be among the strong ions.

Mitochondrial electron transport pathway and particular mitochondrial distress produce reactive oxygen species, and such oxidation species can result in lactate and NADH increases. The electron transport pathway or oxidative phosphorylation involves freeing of 2eV- from hydride which excites the transport pathway members with fluorescent energy that is apportioned in an equal democratized way among the complexes of the electron transport pathway. 58 percent of such 2eV- quanta are utilized for operations within the pathway and about 42 percent is integrated as hydride into the oxonium nestled between the phosphate groups of atp and in the extremity oxonium in atp. Atp is attached to methionine by s – adenosyl methionine synthase to produce s – adenosyl methionine that stimulates a carbocation rearrangement in which the hydride from ATP is shifted into the methionine molecular structure, causing an ionization of the sulfur. Thus, when PEMT removes CH3 from s – adenosyl methionine, the CH3 has a specialized or differentiated characteristics before it is removed by PEMT. The lone pair of electrons in CH3 are then attached to the three open locations of the nitrogen in phosphatidylethanolamine in three sequential methylations to produce de novo choline as enriched phosphatidylcholine.

Phospholipid cycling interconversion, and fatty acid shuffling by lands cycle freeing of phospholipids and fatty acids through phospholipase and phosphodiesterase activity, followed by land cycle reintegration of lysophosphatidylcholine and free fatty acid into phospholipids with shuffled fatty acids, produce polarity stabilization because the different fatty acids and phospholipids have different oxidation status, different polarities and different structural ability to integrate, store, or exchange redox factors.

Importantly also is the observation that glycolysis is a primitive reactive oxygen species regulator, such that downregulation of glycolysis can displace this primitive and capable modality of reactive oxygen species regulation. This describes another mechanisms through which PEMT downregulation promotes processes correlated with detrimental aspects of aging.

Lactate causes mitochondrial distress, except in neurons in which lactate promoted reactive oxygen species which enhance mitochondrial energy metabolism and derive oxidative statuses I which hydride or hydrogen is release, although it is known that an obscure mechanism exists through which reactive oxygen species becomes commandeered by peroxisomes to produce oily substances such as dolichol and produce fatty acids through fatty acid beta oxidation.

CO2, in the warburg toggling of pyruvate directionality, can be directed toward fatty acid synthesis.

Pyruvate can be directed toward many pathways linked to redox or NAD+/NADH balance, including toward acetaldehyde and then ethanol which involves NADH/NAD+ translation, phosphoenolpyruvate involving ATP/GTP exchange for ADP, Phosphate and GDP although phosphoenolpyruvate can then be shunted into glycolysis again, transamination involving amino acid alpha-keto acid bidirectional exchange toward alanine synthesis, oxaloacetate synthesis involving (HCO-)3/ATP conversion to ADP/Phosphate followed by shunting of oxaloacetate into the krebs cycle, lactate involving exchange of NADH to NAD+, acetyl-CoA/CO2 involving NAD+/CoA exchange for NADH followed by directing of CO2 toward fatty acid synthesis and directing of Acetyl-CoA toward krebs cycle and toward choline acetyltransferase activity. All of these involve redox cycle systems, carbonate buffering system and tissue involved in lactate metabolism, redox and carbonate buffering.

The literature and data observe that dissolving of CO2 into water results in cycling between Carbonic Acid and Bicarbonate until equilibrium is reached, in a way that the numerous factors that change this equilibrium participate in as buffering systems. The objective of the bicarbonate buffering system in physiology is to maintain background ph near 7.2 to 7.6, specifically near 7.35 to 7.45 and particularly at ph 7.4. This ph provides background gradient that enables activity to occur between hydride H2e1p, hydrogen H1e1p and H+ H0e1p or other hydrogen oxidation statuses. The strong ions function upon this background gradient within hydrogen isoforms and redox exchange functions upon this background gradient, while other systems contribute to maintaining this background ph independent of and interactively with these systems.

CO2 and bicarbonate are major constituents of ph in circulating fluid while hydride outside of this context in cellular membranes, in circulating or structural CH3, all can be factors in background ph other than only in circulating fluid. Phosphatidylcholine, phospholipids, cysteine, pulmonary, hepatic, renal and other function participate in carbonate buffering, as does glycolysis. Rate of pulmonary respiration and pulse can also participate in the carbonate buffering system. However, generally, all of biological function participates in the shuttling, transfer, exchange, obtainment, eluting, release and recapture of hydride as H2e1p, other versions, NAD+, NADH, NADP+, NADPH, other hydride carriers or 2eV-, e-, current, fluorescence, or translation of these into mechanical force or translation of these into thermodynamic influence or pressurization influence.

Some of this buffering and redox sustaining system is focused on producing insulated contexts such as cellular membranes, endothelial areas, luminal areas or tissues which capture freed hydride as e-, hydride, 2eV-, fluorescence, thermodynamics, or pressurization, particular to enable capacitant fields that comprise cognitive contexts and enabled consciousness, optimal cognition and sustainable, controlled and directed biological function known as behavior.

Thus, out of the hydridic zero-point field that encompasses the universes and interacts into antecedent eras and into future eras, these systems maintain focused integration of these universes level energy sources which power the stars and celestial entities of the Universe, into individual instances of being beginning with the capacitant fields that emerge at conception when interaction with the external environment begins to shape these fields into beings. Thus, capacitant fields comprising beings do not begin with conception and do not conclude at abated vital being, but are focused into a system of development, improvement and focused interaction with external system between conception and abated vital being. Conscious vital being may be distinct from vital being in paralytic statuses, and the zero point hydridic field encompasses the universes and supplies hydride for celestial entities, production or eluting of light, and translation between light, current, other versions of capacitance, e-, particle and wave multiplicity of material of the universes. CH2 or methylene bridges efficiently translate e-, light, current, electrons and wave functions into polymerization potential, structure and useful forms of hydride including hydride and CH3.

2hydrogen phosphate and its ions and hydrogen phosphate and its ions are integral foundational factors that resist change in pH in circulating fluids and affecting physiology otherwise, particularly being more substantial in the intracellular environment than acidic ions and basic ions otherwise. Importantly, when ions are transported into the intracellular environment, some of their hydration shell is skimmed off, producing an intensification of the ions compared to the hydration shell, resulting in strongly enhanced affect to the intracellular environment. Transmembrane protein and ion channels participate in this endocytosis translation system.

Ph, canonically, is calculated by ascertaining the concentration of hydrogen ions or H+. H+ levels, when increased, are correlated with lowered ph or acidity. OH- hydroxyl ion concentration, when increased are correlated with alkalinity or increasing ph. However, these are interactions in fluid and occur upon a context of alkalinity promoted by background hydridic fields. Hydridic fields in the background can be actual in promoting alkalinity or can be cyclic such as the mining of hydride by phospholipases/phosphodiesterases to free membrane packed CH3 for entry into energy metabolisms. The literature characterizes oxides, hydroxides and oxyhydroxides as cationic molecules in which an anionic -O oxygen or anionic hydroxyl group -OH or and oxygen with a hydroxyl -OOH is exhibited with a Cation, with examples of Al, Fe, Mn or Ti as cationic components.

Information) “Hydroxides and Oxyhydroxide Minerals.” Encyclopedia of Sediments and Sedimentary Rocks. Pages 366 to 368. ISBN 978-1-4020—3609-5.

Calculations of H2O dissociation present a bidirectional association between the H2O in liquid status with dissociated H+ in aqueous solution and OH- in aqueous solution, or H20(l) <=> H+ (aq) + OH- (aq). However, in biology, H+ rapidly integrates into other molecules, particularly integrating into other H2O molecules to produce H30+ or hydronium ions.

Hydroxide ions, OH-, however, can freely distributed themselves in fluid. However, the literature observes that hydride ions within hydroxide hosts can be obscured by the hydroxide Oxide component correlated to the distance of the hydride ion component of the molecule from the oxide component nucleus, or a function of electropositivity characteristics.

Group1 and Group 2 metal hydrides are readily combustible in atmosphere. Group1 and Group2 hydrides are also combustible when exposed to water, explaining how these are fuels for catalytic activity and are used to power celestial entities or stars. Hydrolysis of coverts the hydrides in this context into hydroxide and hydroxides may be emulsified in oils to prevent combustion. The chemistry consensus seems to be that organic hydrocarbons are conserved as hydrides of carbon. Particularly, a canonical hydride occurs when hydrogen integrates with another element resulting in an oxidations status that is correlated with, revealing of and determined by the electronegativity of the atom to which hydrogen has become integrated with. Oxidation status is characteristic of how the hydride interacts with the environment. A canonical hydride has a hydrogen within an S2 electron configuration making it H-, exhibits group1 IA and group 2 IIA metals, has an ionic radius between that of fluoride and chloride, has ionic and radius approximating the radius of oxide, mimics halide ion in the solid state. However, hydrogen an exhibit integration with Atoms generally while some of the literature presents exceptions and other literature debate these exceptions.

Information) “Hydrides.” Libre Texts Chemistry website,

Hydroxyl groups are also interested because an attachment locus for hydroxyl groups are exhibited in the typical hormone structure, and balances between the redox version of major hormones change with NAD+/NADH balance, such as NADP+ potentiating of dhea, androstenedione, estrone and cortisone compared to NADPH potentiation of androstenediol, testosterone, estradiol, and cortisol, while star protein encapsulation of cholesterol at cellular membranes stimulates shield transfer to the mitochondria where carnitine shuffling participates in endocytosis of star protein shielded cholesterol, followed by cytochrome p450 synthesis of pregnenolone from cholesterol to being steroidogenesis.

Some the literature observes that at conception it is the ratio of mitochondrial cholesterol entry in this regard compared to aggregation of cholesterol outside of the mitochondria which determines anatomical gender, although since capacitance is strongly enabled by the hundreds of mitochondria in each cellular entity and these hundreds of mitochondria conditionally share connected mitochondrial associated membraned with endoplasmic reticula such that dissociation, association, and functional exchange of metabolites can also determine how capacitance is linked to anatomical structure.

Research linked to this analyses also has found that advance phases of virtually all disease and detrimental nuances of aging typical involve disruption or dissociation of the mitochondrial membrane, isolation of the mitochondria’s supply of newly synthesized phosphatidylethanolamine, deterioration of mitochondrial PEMT2 function as a development regulator that emerges near birth, and, thus, isolation and deterioration of the cdp-choline pathway in mitochondria, and, thus, allowed proliferation of the cdp-ethanolamine pathway in endoplasmic reticula in a context of PEMT1 function that does not have newly synthesized phosphatidylethanolamine, result in antihistamine support of cellular viability along with PEMT1 function that uses phosphatidylethanolamine that is recycle or heavily glycosylated including recycled or already utilized methylene bridge within such recycle phosphatidylethanolamine. Methylene bridges have the potential to deteriorate or become obscured by glycosylation and other reactive molecular species. Methylene bridge cysteine has the potential to impair atom to atom adhesion and associations, and these may possibly include effects to methylene bridge carbons and hydrogens. The information in this context suggest that hydride may be sequestered by methylene bridge cysteine and since organic carbons are considered to be hydrides, the potentially of methylene bridge causing changes to methylene bridges has to be considered.

Information) “Hydride Ions in Oxide Hosts Hidden by Hydroxide Ions.” Nature Communications. Volume 5. Article Number 3515. 2014.

It is not clear why some of the literature presents hydroxide as oxyhydroxide other than differences in analytical contexts, although, oxyhydroxide is suggested to be hydroxide integrated into other atoms, while in biology these present a context of reduced hydroxide.

Iron is mentioned in biochemistry because its correlation to rust, including green rust, is considered to be a foundational disequilibrate that enables displacement of ph compare to pure water ph at 7.0 in enablement of redox or gradients which enable animate biology. Irons occur in about 16 or more configurations that include cations Fe2+, Fe3+, oxygen hydroxyl, water, SO42-, CO32-, Cl-, FeO wüstite, Fe(OH)2, FeIIFe 2 IIIO4 magnetite, F2O3 hematite, FeOOH goethite, Fe5O7.5.4H2O ferrihydrite, and Fe8O8(OH)5.5(SO4)1.25 schwertmannite.

Information) “Iron Oxides, hydroxides and Oxy-Hydroxides.” Encyclopedia of Astrobiology. 978-3-642-27833-4.

The literature observes that hydride may be the only anion that does not have a pi orbital, such that when it integrates into other atoms, it can perform as blocker of pi orbitals.

At least some of the literature ventures to present intracellular cytoplasm ph as typically 6.8 instead of only presenting the pKa of 7.21, revealing an intracellular/extracellular gradient of about.0.6. Thus, inherent capacitance under physiologically typical conditions.

The literature and experimental analyses observe mitochondrial ph near between 7.2 to 8.2, although about ph 8.0 is presented as a general pH that can increase resultant of changes in metabolic stimuli or can be different among cellular phenotypes. Changes to mitochondrial tissue modeled on brown adipose cellular phenotype and differentiation observes triphasic change in mitochondrial pH with increases in pH in two incipient phase occurring before thermogenesis in correlation with increase Ca2+ transfer from the endoplasmic reticulum, followed by decrease in pH during thermogenesis. Studies otherwise present proton motive force as a stabilizer of alkalinity s the electron transport pathway moves protons in and out of the mitochondrial membrane. However, generally, a study observes alkalinity increases in the mitochondria are correlated with potential for apoptosis and decreases in alkalinity are correlated with exhibition of autophagy.

The chemical gradient for protons ΔpHm and mitochondrial membrane potential ΔΨm each have at least independent influence in potentiating proton motive force Δp which characterizes the potential for performance of ATP synthesis. This confirms correlation between hydride, 2 eV- and fluorescent capacitant released during the electron transport pathway and mitochondrial capacitance occurring when these are captured by the mitochondria membranes and released in coordinated exchange of protons between mitochondrial membranes and cytoplasm as phases of the electron transport pathway advance.

Information) “Mitokyne. A Ratiometric Raman Probe for Mitochondrial pH.” Anal Chem. Volume 93. Number 37. Pages 12786 to 12792. 2021.

Information) “The Renaissance of Mitochondrial pH.” J Gen Physiol. Volume 139. Number 6. Pages 415 to 423. 2012.

Information) “Triphasic pH Changes in Mitochondria.” Mol Metab. Volume 6. Number 8. Pages 797 to 808. 8th Month, 2017.

The Endoplasmic Reticulum is presented by the clinical information to present a typical pH of about 7.2. The Golgi Apparatus, according to the available information, exhibits a pH of near 6.7.

The clinical information presents the cytosol at near pH 7.0 to 7.5.

The clinical information presents lysosomes as having near ph 4.5 to 5.0. This pH must be focused on lysosomes that have developed and are in acidic statuses required for applied function.

The clinical information presents autosomes as having ph 4.5 to 6.5 with autophagosomes about 6.0, early autolysosomes about ph 5.6 and mature autolysosomes at about ph 5.2.

Information) “Modulating Lysosomal pH.” J Life Sci (Westlake Village). Volume 2. Number 4. Pages 25 to 37. December, 2020.

Information) “Quantitative Analysis of Autophagic Flux.” Autophagy. Volume 11. Number 10. Pages 1905 to 1916. October, 2015.

Oncology is presented as have increase alkaline cytosolic pH above 7.2 and extracellular acidity below 6.8 resultant proton overload from lactate fermentation and hydration of CO2 described as directing of pyruvate and nadh directed toward lactate anion and nad+ in from PEMT downregulation and P53 upregulation in anaerobic glycolysis being persistent when glycolysis becomes dysregulated in these same conditions to constituted aerobic glycolysis. Enzymes used in oncology to proton overload include phosphofructokinase, hexokinase, lactate dehydrogenase, pyruvate kinase and carbonic anhydrases, providing therapeutic potential if these can be safely downregulated or inhibited in oncology.

Preventing extracellular acidity and preventing increases in cytosolic alkalinity can be useful therapeutic objectives.

Consensus consideration of lysosome acidity as an enabler of Ca2+ influx into lysosomes has been countered by observations that the downregulation of the V-ATPase H+ pump was not able to prevent refilling of lysosomal Ca2+. Agonists of Endoplasmic Reticulum IP3 Receptors, or IP3Rs, rapidly prevented lysosome refill with Ca2+. Similarly prevention of lysosome Ca2+ refill occurred when Endoplasmic Reticulum Ca2+ was depleted. This preventing of lysosomal Ca2+ refill produce a lysosomal storage phenotype that was correlated lysosomal storage disease.

Lysosomal storage disease vary with some being among the general group of metabolic disoders and some being linked to particular aspects of gender specific chromosomes. The literature presents particular patterns in Lysosomal disorders, although these can vary with causality. However, this compendium of research observes a diverse group of mechanisms through which conditions influences are enabled to cause disease. Thus, phospholipase D3 is increased in lysosomal disorders along with being coprecipitated with amyloid and tau in alzheimer’s disease. Peroxynitrite and iNOS upregulation and the ability of iNOS to deplete Ca2+ because iNOS has an already integrated calmodulin that constitutively sequesters four molecules of Ca2+ per iNOS protein instances, each are presented in nuances of lysosomal disorders and alzheimer’s disease. Particularly, iNOS depletion of Ca2+ produce a syndrome that links diverse nuance of alzheimer’s and lysosome disorder characteristics. iNOS depletes store operated Ca2+, causes perforations in the endoplasmic reticulum interaction with the plasma membrane to produce openings into the extracellular environment which deplete intracellular and extracellular Ca2+, deplete L-arginine, deplete myelin basic protein which has multiple molecules of l-arginine, creates systemic gradients of Ca2+ as it is depleted from bones and reprograms distal chemokine migration including progenitor cellular entity migration, exhibits such force that cellular entities can become disintegrated with endothelial tissue, cause collapse of the sarcolemma, cause amoeba shaped of cellular entities, causes uncoupling of iNOS to produce reactive molecular species, causes uncoupling of eNOS and uncoupling of nNOS because of iNOS depletion of Ca2+/L-arginine resulting in reactive molecular species production, and reactive molecular species deactivate biologically active molecules and fuse together bundles of proteins that occur in autophagy and proteolytic targeting factors such as ubiquitinases which result in inability to enzymically deteriorate bundles which impairs proteolytic and autophagic efficiency.

Also, while the literature observes mitochondrial impairment as factor in lysosome disorders and Alzheimer’s, these analyses analysis observe methylene bridge cysteine above 6 um/L, downregulation of PEMT, upregulation of the choline kinase and the cdp-choline pathway, upregulation of nonresolution phase survival signaling including choline kinase alpha, proteolysis, impaired autophagy, Bax, Bak, S1P availability, S1P receptors, GCPR receptor activation GSK3b and other factors in this group of factors. These result in eventual dissociation of the mitochondrial associated membranes that links the endoplasmic reticulum to the hundreds of mitochondria that can be in cellular entities, also resulting in impaired exchange of Ca2+ to the mitochondria, impaired transfer of newly synthesized unglycosylated phosphatidylethanolamine from mitochondria to the endoplasmic reticulum, and impaired exchange of phosphatidylinositol, Inositol, Phosphatidylserine, Ca2+, phosphatidylethanolamine and other metabolites between this organelles once they have become dissociated.

However, it is the downregulation of mitochondria numbers, mitochondrial membrane potential, level of available ATP which decreases because of both mitochondrial dysfunction which impairs electron transport pathway and decreased mitochondrial number, which together potentate the group of symptoms and syndromes link to pervasive lysosome disorders and alzheimer’s, while all of these share much of this pathology pattern with all disease.

Other diseases relevant to lysosomal storage disease includes glycogen storage disease, although the literature presents these as polymorphism of specific genes involved in glucose metabolisms, particularly involving impaired integration of glycogen into amyloid fibers, impaired release of glycogen from amyloid fibers, but also including reactive molecular species or glycation end product, lipoxidation end product, ascorbylation end product or other end product enabled fusion of intermediary bundles or intermediary tangles in proteolysis, autophagy, ubiquitylation or other pathways.

However, glycogen is upregulated in pemt downregulation, P53 upregulation responsive to pemt downregulation or P53 upregulation in response to impairment or injury. Inhibiting P53 or enabling upregulation of pemt may diminish glycogen storage diseases. Also, diverse hexose sugar supplementation circumvents P53 inhibition of glucose – 6 – phosphate dehydrogenase which is the entry point of glucose into glycolysis and the pentose phosphate pathway. Diverse hexose sugars also circumvent P53 downregulation of GLUT which is a primary pathway through which glucose is endocytosed into the intracellular environment.

Active hexose correlated compound, phosphatidylethanolamine, DHA, phosphatidylinositol, inhibitors of iNOS such as Curcumin/Coumarins/Imperatorin along with pharmacological inhibitors of iNOS, inhibitors AP1 including Berberine, inhibitors of SP1 including Curcumin/Coumarins/Imperatorin/Irinotecan or pharmacological inhibitors, leaky gut therapies such as pre/pro/macrobiotics, olive oil, grape seed oil and diverse coverage antibiotics, and diverse mechanisms of downregulating methylene bridge cysteine including enlyte/enlyterx, 6s methyltetrahydrofolate with vitamin B12, S methylmethionine sulfonium with B6, Niacin, methyl sulfonyl methane, lecithin, niagen, melatonin, bergamottin, imperatorin, beet powder or trimethylglycine, EMF Protection, Pregnenolone, a diverse mineral supplement, a diverse vitamin supplement, filtered water, and only A2 version of dairy products. L-arginine, Ca2+, Vitamin D, Vitamin K2, Potassium are useful metabolites in this context. Potentially, also, phosphate, could assist in balancing metabolites.

Information) “Mitochondrial Ca2+.” “Cellular Calcium.” Volume 44. Number 1. Pages 103 to 111. 7th Month, 2008.

Information) “Mechanisms.” J Clin Med. Volume 9. Number 8. Page 2596. 8th Month, 2020.

Information) “Lysosomal Calcium Channels.” ’Oncology’ (Basel). Volume 13. Number 6. Page 1299. 3rd Month, 2021.

Information) “Rewiring pH.” ‘Oncology’ (Basel) Volume 12. Number 9. Page 2437. September 2020.

Information) “PLD3.” PLoS Genet. Volume 17. Number 4. e1009406. 2021.

Information) “Cellular Pathophysiology.” in Fabry Disease.

Information) “pH of Endoplasmic Reticulum.” B10NUMBE3R5. Bionumbers Database of Useful Biological Numbers.

A more intricate observation of major buffers includes CO2 entry into physiological fluid as CO2 integration with water to produce carbonic acid, H2CO3, while in pulmonary tissues and function, H2CO3 is converted into water and CO2, such that CO2 is excreted or expiated. Surfactant production of surface tension promotes escape of CO2 and obtainment of O2 to assist in assured efficiency of pulmonary performance of O2/CO2 exchange. Thus at least some of O2/CO2 exchange in alveolar contexts result from surface tension and do not specifically and do not only occur with muscle or mechanical function, although the system of pulmonary function including muscle function is essential to physiological homeostasis.

Bicarbonate anion (H2CO3)-and Carbonate (H2CO3) are interactive factors in physiology which affect pH. H+ increases potentiate Carbonate increases while H+ or hydroxide increase potentiated Bicarbonate increases. Hydroxide Ions do not require integration into other molecules, but can become integrate as oxyhydroxides, while hydride does not occur in typical conditions as a free hydride anion, suggesting that it is hydride that is counteracting H+ and it hydride that is integrated into Hydroxide.

Information) “Acids, Bases, pH, and Buffers.” Biology Library. Website.

Sucro ferric oxyhydroxide is instrumented to support diabetic conditions in early development. FeII and FeIII oxyhydroxide, or green rust, is suggested to be essential in the early transition of biota from inanimate to animate activity. Particularly, green rust participated in mixing of carbonic ocean contexts with alkaline hydrothermal fluids. These contexts may have been important nuances of the interactive and cyclic interactions that fulfilled the incipient impetus toward biology, Life and animate Life. Cobalt, nickel, and molybdenum along with iron, would have participated in producing bio-syntonic disequilibria and modalities in which such disequilibria may have been applied to produce differentiated contexts linked to animate being. Endergonic reactions enabled by hydrous green rust interlayers, enabled by steep ionic disequilibria, may have powered the ability to satisfy the developments which satisfied the impetus for the exhibition of animate being. Sulfide and elements would have been able to enable catalytic activity, perform as electron transfer agents, become reduced to ammonia, synthesis formate, in context of methane being oxidize to methyl groups and formyl groups, all involving sulfides, trace elements, nitrate, CO2, and methane. Higher carboxylic acids and acetate, emerged from C1 molecules toward aminated amino acids, phosphate and iron sulfides, along with synthesizing of primitive amyloid structures, all were possible in this context in a way that increasingly potentiated prokaryotic cellular function. This observation is less a philosophical assertion than it is an example of how redox and ph are important in enabling foundational activity linked to sustainable being and Life. Particularly, these contexts may have performed as testing grounds for guided and stabilized metabolism.

Information) “Green Rust.” Life (Basel). Volume 8. Number 3. Page 35. 2018.

Information) “Sucroferric Oxyhydroxide.” Pediatr Nephrol. Volume 36. Supplement 1. Pages 1 to 12. 10th month, 2020.

Information) “Guided Metabolism.” Front Microbiol. Volume 14. 1145915. 2023.

Buffering systems can be comprised of weak acid which abdicates hydrogen ions and a weak base which accepts hydrogen ions. Ph is maintained in this way because when ions are added to such a buffering systems solution, the weak base sequesters the excess ions and become changed to be components of the acid in the system. A base, when introduced into the system, the weak acid abdicates its ions, some of which then become changed into the weak base, and the solution is moved toward acidity. The result is a balancing of the solutions and system.

The phosphate buffer system maintains the intracellular ph in all living organism. 2hydrogen phosphate ions perform as the weak acid and hydrogen phosphate ions perform as the weak base, while these typically and even always will interact in fluid or intracellular fluid to produce an equilibrium represented by pKa or dissociation constant. pKA is typically 7.21 which near the physiological ph of 7.4.

The 2hydrogen phosphate ions and hydrogen phosphate ions may be exhibited in inadequate volume to maintain systemic ph among the circulatory pathways, requiring bicarbonate ions as the weak acid and hydrogen carbonate ions as the weak base.

Ph is defined as potential of hydrogen or the potentiometric hydrogen ion concentration. This reflects the concept that acids produce interactions with other material, referentially presenting the concept of acids. Bases, however, produce an increase in activity among hydroxide ions when introduced into water, contrasting the increase in activity among hydrogen ions which occurs when an acid is introduced into water. Pure water has ph of 7.0 at 77 Fahrenheit and changes in ph represent logarithmic 10 times change in availability of the ion which potentiates the directionality of the change.

CO2 introduction into water to produce carbonic acid, followed by dissociation of carbonic acid into hydrogen ion and bicarbonate. Enzymes can catalyze inverse reactions to carbonic acid dissociation into hydrogen ion and bicarbonate.

pH changes can affect the coagulation potential of erythrocytes, while different phospholipids exhibit different polarity and oxidation statuses that promote or depromote platelet activation and aggregation, such as phosphocholine produced by choline kinase alpha which is an activator of platelets. Bones also supply minerals used in the ph buffering mechanisms. iNOS/NOS2 expression produces systemic gradients in Ca2+ that release Ca2+ from bones, increasing circulating Ca2+, requiring vitamin K2 to counteract such conditions and changing the patterns of migrating stem cells and migrating monocytes, sometimes with such force applied by cellular entities with pores opened from the endoplasmic reticulum through the plasma membrane and into the extracellular environment that L – arginine depletion, Ca2+ deployment, myelin basic protein depletion, collapse of the sarcolemma, amoeba shape of the cellular entity and spontaneous transition to mesenchymal migration from endothelial integration can occur.

Information) “What is Carbonate Buffering.” Website.

A foundational calculation in ion balance includes the Base excess calculation as BE = Z x [[cHCO3=(P) – C7.4 HCO3-(P)] + beta x (pH – 7.4)].

Information) “The Accuracy of Calculated Base Excess in ‘Hematopoietic Fluid’.” Clin Chem Lab Med. Volume 40. Number 4. Pages 404 to 410. 4th month, 2002.

A popular multiple parameter calculation is presented as the following.

[H+] x [OH-] = K ‘w(water dissociation equilibrium)

[H+] x [A-] = KA x [HA] (weak acid equilibrium)

[HA] + [A-] = [ATOT] (conservation of mass for “A”)

[H+] x [HCO3-] = KC x PCO2 (bicarbonate ion formation equilibrium)

[H+] x [CO32] = K3 x [HCO3-] (carbonate ion formation equilibrium)

[[SID] x [H+] – (HCO3-)-] – [A-] - [CO32-] – [OH-] = 0 (maintenance of electrical neutrality)

Although other calculations include the strong ion difference, ATOT, PCO2 and other considerations.

Information) “Strong Ion Difference.” website. October 26, 2022.

The anion gap is calculated as (Na+ + K+) – (Cl- + HCO3-) = Anion Gap which can be changed to reveal or elute information about unmeasured cations and anions which have become promoted to be among the strong ions using

([Na+] + [K+] + [UC]) = ([Cl-] + [HCO3-] + [UA])

Information) Biochemistry, Anion Gap. website.

B vitamin niacin and niacinamide, along with pathways such as NAMPT and circadian rhythm pathway factors such as melatonin, crust and mantle magnetic fields, fields from sunlight, and e- being directed toward earth from extraterrestrial origin, provide a perspective of electron, hydride and NAD+/NADH recycling and synthesis.

The interesting context of reactive oxygen species and phospholipids, includes the management of methylene bridge cysteine by THMT methylene bridge cysteine dimethylthetin methylpherase. Inadequate sulfur results in deactivation of THMT by producing intramolecular disulfide linkages that produce a gelatinous inactive phase for this most abundant enzyme. There is a reasonable correlation between why this useful enzyme to depleting methylene bridge cysteine becomes deactivated, and such correlation includes the great oxygenic event in which the ratio of atmospheric sulfur was decreased along with increases in atmospheric oxygen resultant of increase abundance of rubisco enzyme availability but also probably in correlation with other events. Importantly, less adequate sulfur can be counteracted during hibernation in which hibernating organisms may be in enclosures that may change the balance of oxygen/sulfur and in which metabolic conditions are changed to produce less ability for oxygen and less ability of reactive oxygen to cause metabolic remodeling and structural remodeling. There does not seem to be much data that observes differences in levels of reactive oxygen species, distress signaling, and adverse health events differentially exhibited during hibernation in enclosed earth exposed environment compared to adverse health events otherwise.

Information) “Base Exchange in Sir2 Enzymes.” Molecular ‘Cellular Entity.’ Volume 25. Issue 3. Pages 463 to 472. 2nd Month, 9th Day, 2007.

Information) “Lactate Metabolism.” Nature, Signal Transduction and Targeted Therapy. Volume 7. Article Number 305. 2022.

Research observes that instrumentation of lactate oxidase and catalase to loci of highly pathogenic neoplastic oncology was highly disruptive and of therapeutic potential.

Information) “Lactate Oxidase/Catalase Nanoparticles.” Journal of Nanbiotechnology. Volume 21. Article Number 5. 2023.

Information) “Lactate Physiology in Health and Disease.” BJA. Volume 6. Issue 3. Pages 128 to 132. 7th Month, 2006.

Lactate oxidase does not seem to be a Human enzyme.

Information) “12 Facts About Lactate Oxidase.” Website.

Some factors such as methylene bridge cysteine, which must be managed to 6 or 7 um/L, because it can be promoted to be among the strong anions because it has a negative aggregate polarity, although methylene bridge cysteine is known to be produced by removal of negatively polarized methyl group that exhibits a lone pair of electrons at such removal of the Methyl groups, and although methylene bridge cysteine is known to methylene bridge cysteinylate structure and molecules in a way that sequesters liv3201ingness or hydridic character from atom level interactions and biological activate molecules. Methyl groups, CH3, harbor a methylene bridge as CH2 and harbor hydride as H2e1p among the 2 other molecules of Hydrogen as H1e1p.

PEMT is important because it stores CH3 by sequentially attaching CH3 to the three open positions of the Nitrogen in phosphatidylethanolamine’s lead group of ethanolamine. The hydride in methyl groups integrated into phosphatidylcholine, produced by PEMT from phosphatidylethanolamine methylation, exudes negative polarity into the microenvironment, along with the polarity of fatty acids in the sn-1 position in particular, which balance lead group polarity in phosphatidylcholine. The hydride can be mined or obtained by freeing of phosphatides, fatty acids and lead groups during phospholipase or phosphodiesterase catabolism of phosphatidylcholine or phospholipids from cellular membrane during nonresolution phase, choline inadequacy or other metabolic conditions.

DBC1 integrates with sirt1 but experiments indicate that other factors inhibit sirt2. Nicotinamide which is detoxified by nicotinamide methyltransferase or recycled into NAD synthesis, downregulates sirt2, explaining how, with advancing age, sirt2 increases and sirt1 decreases. Sirtuins are deacetylases.

Sirt2 does not disrupt sirt1 deacetylation of tubulin.

P300 enables acetylation of P53 and DBC1, counteracting sirt1 deacetylation of P53.

A selective inhibitor of Sirt 1/2/3 was cytotoxic to diverse oncology cellular examples. A selective inhibitor of Sirt2 was also cytotoxic to diverse oncology cellular examples although with lower potency that inhibitors of sirt 1/2/3. Small nonhuman mammals were toxically affected by the sirt 1/2/3 inhibitor, had similar cytotoxicity from inhibitors of sirt1/2/3 and inhibitors of sirt 2 specifically, all suggesting that human sirt 1/2/3 are differently essential or enjoy different biological reliance, larger anatomical mass and more substantial detoxification systems as a defense to toxicity.

Information) “Pharmacological Advantage of ‘Selective’ SIRT2 ‘Inhibition’ Compared to ‘Sirt1/2/3’ Inhibitors.” ACS Chem Biol. Volume 16. Number 7. Pages 1266 to 1275. 2021.

Sirt1 exhibits two CK2 casein kinase 2 interaction loci in its ESA essential for sirtuin activity sequence in the sirt1 C extremity. The loci are phosphorylation loci that encapsulate an essential catalytic domain. CK2 phosphorylation of these phosphorylation loci enhances the interaction between the central catalytic domain and the catalytic domains which are disrupted by the CK2 phosphorylation loci. Resultant of phosphorylation at these CK2 phosphorylation loci, sirt1 has enhanced substrate affinity and enhanced catalytic throughput while the ESA domain that includes the phosphorylation loci for CK2 competes with DBC1 integration into sirt1. Thus, Casein Kinase 2 phosphorylation enhances sirt1 deacetylation and displaces DBC1 from sirt1.

Thus, dn-dbc1 is not required to displace dbc1 from sirt1, casein kinase 2 phosphorylation can displace dbc1 from sirt1, and potentially other phosphorylating kinases during a phosphorylation cascade might be able to likewise displace dbc1 from sirt1, potentiating nad+ and nadh or other NAD or hydride carrier integration into sirt1.

Importantly, casein kinase metabolizes casein, particular casein from milk. Human milk and other A2 milk sources exhibit a different substrate profile from nonA2 milk. nonA2 milk has an increase phosphorylation activity by the protein kinase CK2 or casein kinase 2. A1 beta casein is typically present in nonA2 milk, whereas A2 milk typically exhibits only A2 beta casein. The A1/A2 combination in nonA2 milk is linked to pathologies, diminished behavior and diminished health status, while A2 milk does not have such a correlation, particularly resultant of enhanced phosphorylation generally in nonA2 milk or increased exhibition of A1 beta casein as substrate for CK2. The casein kinase upregulation or change resultant of A1 beta casein as substrate may be reflected in sirt1 ESA phosphorylation frequency, potency or completeness. Experimental separation of the A1, A2 and other genetic variants of mixed milk occurred using a hydrophilically coated capillary at low ph in pasteurized skimmed farm milk, such that hydrophilicity and ph both represent changed or characteristic function in metabolic, circulating and structural contexts. The 67th Amino acid in beta casein is different in A2 than from A1, while the 67th protein of the A1 beta casein enables synthesis of BCM-7 whereas A1 is not able to derive BCM-7.

Histidine occupies the 67th amino acid in A1 milk and proline occupies the 67th amino acid position in A2 milk. Histidine is susceptible to human digestive enzymes to enable release of beta casomorphin-7 in correlation with digestion or during cheese ripening. Proline at amino acid 67 is less susceptible in this regard. Beta – casomorphins are able to integrate with opioid receptors of the gastrointestinal pathways and central neurological system. Digestive pathway functional status and conditions of menstrual cycling, both can typically be improved by using A2 diary instead of A1 diary. A1 milk is linked with early developmental risk after conclusion of gestation, explaining why the most developed western civilizations have early development and maternal risk profiles comparable to underdeveloped and developing civilizations. Also linked to A1 dairy is diabetes type I, developmental autism and atopic dermatitis, much of which include increased ability of beta-casomorphin 7 to permeate digestive pathways, presumably including activation of cytokines that relax tight junction proteins. These factors may be components of leaky gut syndrome. Cardiovascular conditions and neurological orders are included in such linked disease.

However, there are other locations for amino acid substitutions among the prominent polymorphism at amino acid position 67 including in A3, I, B, C, D, E, F H1, H2 and G, with histidine being represented at amino acid position 67 in B, C, F ang G variants. Lysine is also substituted in at amin acid 18 for D variant, and leucine is substituted in at amino acid position 93 for variants I and H2.

The debate has been that some studies exhibit no conclusive confirmation of A1 toxicity, which is often the result of the gold standard in clinical studies which use blind, double blind, randomized, placebo enabled studies that are pervasively flawed because the cause of pervasive disease is methylene bridge cysteine above 6 micromoles per liter while pervasive therapies cause increases in methylene bridge cysteine, making most studies moot because therapies often merely intensify the symptomology and alleviate symptomology but allow methylene bridge cysteine levels to persist, increase, and promote other pathology. The promoting of continued reemergence and casting of pathology into different emerged symptoms or complications enhancing billing benefits, increases drg levels, length of stay and level of impairment, resulting in enhanced revenue or enable outlier payments because drgs are calculated based upon particular standard lengths of stay and levels of services provided.

Chargemaster apportionment of inpatient or outpatient facility expenses to the billing process can include distant in antecedent era costs and have the potential of being overly represented in large amounts that are billed to consumers and health expense indemnification coverages or health plans.

The political, social, economic and systemic analysis presented in this analysis are important because these factors cause disease, result in disease not being adequately resolve, and cause diminished outcomes including diminished physiological outcomes. Importantly, such presented contexts show clearly that systems have an in inherent propensity to prioritize themselves over the incipient impetuses, priorities and utility of civilization, over other systems that also may or many not adequately prioritize such incipient impetuses and priorities of civilization, and over Humanity. Thus, instead of the rational basis of the priority of Life, Liberty and Pursuit of Happiness, systems have the propensity of self-prioritization, which is anathema to the intent of systems as being the silver frame that assures the golden apple priorities of Life, Liberty and Pursuit of Happiness. Like any system, but particularly of a system derived upon the priorities of Life, Liberty and Pursuit of Happiness, outcomes among its processes merely elute into observability how adequately such systems dispense with Human welfare assurance, Social Welfare assure, assurance of Human Requirements, Social Requirements, Behavioral Requirements and Physiological requirements. Each diminished outcome represents inadequate satisfaction of such requirements and pervasively have intricate details that are remarkably reflective of the patterns produced resultant of inadequacy and which elute temporally disjoint, observationally disjoint, informationally disjoint, sometimes novel, details into observation, derivation, consideration, understanding and potential resolution. All of human systemic activity have a propensity to serve the priority of sustaining physiology, individual capactitant fields, aggregate capacitance of populations, and dispensing with of these eluting mining processes for information, understanding and wisdom, in a way that enables Humanity to become, or fulfill its role, of acting and moving in increasingly concerted benefit to individual, groups, populations, civilizations, the biome, and the universes. Detrimental nuances of the status quo which are unresolved and which diminish Human priority come to inform the universes a diminished priority for humanity that is anathema to the inherent favor afforded to Humanity by the Universes, by the creative forces of the Universe and afforded to Humanity by its increasingly reasonable, rational, competent, capacitant, beneficial and productive conducting of the advancement of the Human experience.

Attributing causality for diminished outcomes to individuals or groups, inadequate ascertainment of incipient, empirical, physiological, social, exogenous causalities, inadequate focus on resolution of such causalities, allowing social constructs to exculpate such causalities as a focus, all result n detrimental nuances of the status quo that allow systems to escape improvement, in a way that prioritizes the system over its incipient circumstance, incipient utility, and over Humanity. These factors are integral to how disease and other diminished outcomes are enabled or allowed to occur. These factor explain diminished Human priority is represented in diminished priority for the environment and biome. These factors also present how systems of the biome and the universe might be impressed into producing diminished human priority as a result.

There is the obvious possibility in this regard that systems may be producing outcomes that elude inadequacy as an inherent and deliberate function that requires acknowledgement of inadequacy and increasingly implores and increasingly cognitive acknowledgement of inadequacies and promoting of these to the institutional agenda.

Importantly, most of the services billed for by facilities and sometimes billed in office visits are status apportionments because the facilities has not incurred any differential costs resultant of the encounter, intervention or inpatient/outpatient encounter. Although it is not suggested that such contexts should not be reimbursed in a reasonable way, its is observed that pervasively such costs are apportioned not resultant of actual additional expense incurred, such that when these costs emerge as unreasonably high during advanced impairment or concluding phases of care or concluding phases of being, unreasonable outcome are potentiated. Particularly, care entities are able to attach such unreasonable high costs to the estate of those receiving care. Similarly, even needs based or entitlement health coverage programs have obscure provisions that allow the estate and property of those receiving care to be commandeered or used to reimburse for outstanding or uncovered care expenses. These economic practices are inherently unreasonable because the costs are apportioned instead of being actual, bona fide services performed and even when these are calculated rbrvu costs using cpt, apc, drg or other code set provisions, these are likely to be unreasonably high and are mitigated because any reasonable semblance of a civilization should include care as one the empirical, incipient foundations of assuring social welfare and human welfare. Importantly, these reimbursement practices are used to destabilize groups and communities, prevent this fragile context of wealth translation between generations, turn fragile stable conditions into another context in which the inferno of misfortune and diminished outcomes are used to keep subversive patterns impressed into groups and communities which systems can use keep facilities full through roemer’s dynamics.

It is well known that organization can be required to try and obtain excess costs from those receiving care, resultant of provisions in entitlement, needs based and commercial health services indemnification coverage. It is also well known that care costs for the indigent and those not able to satisfy such billed costs can be recovered through indigent care funds, written of during financial analysis and income determination, disappointed using accounting practices, or otherwise diminished in effect, such that when these costs are apportioned to the detriment of the estate and fragile contexts of translation of wealth between generations, care entities in some instances may be receiving treble benefit.

One modality, among ways that these factors can be resolved reasonably is to require that coverage be available to or applied just in time for those receiving care, particularly those receiving costly care. Copays, Coinsurance and deductibles might be implemented but also may include loss prevention coverage that applies to outcomes involving all people receiving coverage and incomplete coverage by all coverage or indemnification plans. The limit of reimbursement or coverage from stop loss might be participate in assuring minimum calculated income for practitioners and other employees, replacing revenues required to continue business operations after an indemnification claim or other event, and produce a continued going concern for the care providing organization or care providing entity. All care facilities and entities should be required to participate in such loss prevention coverage along with or included in malpractice coverage or malpractice indemnification plans. Minimum, experience correlated, quality of care correlated, medical acuity correlated incomes for each practitioner should be assured by local care coverage indemnification plans, practice association or encompassing entities that employ practitioners, local funds, outlier payment funds, pass through payment apportionments, or other arrangement or funds that can be enacted in the public trust interest such as special or general Federal, State, County, Municipal, private, commercial or other contexts.

That which is clear, however, is that differences in billed costs and reimbursement for care should be captured in some arrangement that holds those receiving care harmless and without responsibility, preventing these costs from escaping into groups and communities, preventing the allowing of benefit obtainment from exhibition of diminished outcomes, and, lastly, preventing these from contributing to infernos of misfortune, conjured subversion, impressment into subversion and deterioration of groups and communities as populations move from system to system without any intent of resolving incipient and empirical causality from exhibition of diminished outcomes.

Minimum incomes should be assured directly to practitioners as differentials from income received from independent practice or from employed practice. Every business, private, commercial or noncommercial care entity should have an independent separate nonprofit status persona that is utilized as a test ascertain its apportionment of practitioner income, employee income otherwise, and operating income, all compared to how such entities otherwise represent their economic and financial activity. These are important in observing the potential for underpaying practitioners who prioritize management of methylene bridge cysteine in a way that diminishes recidivism and disrupts patterns of overutilization, increased lengths of stay, outlier payments, pass through payments, other modalities, patterns, and practices that are subservice, promote subversion, victimize practitioners, or victimize populations receiving care or potentially requiring care.

Acuity refers to analytics implementation to determine the pay, number of patients, number of practitioners, volume patients, number of supportive employees, supply levels, and other factors attributed to each practitioner, service context, subsidiary or organization that results in the most optimal quality of care, worker valences, patient valences, most optimal outcomes and minimum level of sustainability. These can include allocation of professional education, peer reviewed journal publications, and synthesis of care or practice guidelines and information tuples. These are important for sustainable, stable, development enabled worker experience in any system.

It is important to consider that apprehension is typically presented when involving changes to how industries perform flow of revenue. This analysis does not diminish the priority of stabilizing economies. However, roemer’s dynamics can be promote in intercivilization interactions, requiring a buffering system that prevents massively influential or massive populations from imposing roemer’s dynamics that cause outcomes which result in use of products, services and outcomes from being increased according to the availability of such products or services instead of the demand for products or services being the impetus for increased available of products and services.

Importantly, some civilizations use fiat currencies that are not linked to a particular source such as gold, silver, platinum, or other factors. Also, the modern era rarely exhibits pricing and demand that is link to availability of natural resources, particularly those resources essential to Human welfare and social welfare. Civilization should be using analytics, parameters, regulation and change that stabilizes economies and systems and implementing mechanisms that assure timely, reasonably priced, and stable access, availability and sometimes provision of those factors which assure greater than poverty level conditions beginning as entitlements at conception. Conditions that enable, allow, promote or impute dynamics that deprioritize human priority should not be allowed to occur in civilizations, particularly because these are anathema to the incipient, empirical impetus for exhibition and sustainment of civilizations. It seems important to analytically delve through and transcend much of the unnecessary, imputed, obfuscative complexity and continue assuring Human priority in civilizations and systems.

A1 beta casein potentiates beta casomorphin-7 resultant of proteolysis that involves the histidine at at amino acid position 67. Pancreatin, trypsin, chymotrypsin, which are proteases, potentiated opioid receptor activating proteins when exposed to beta casomorphin-7. BCM-21, BCM-7, BCM-9 and BCM-13 were among these potentiated opioid receptor activators.

Undeveloped gastrointestinal pathways incompletely digest these beta casomorphins. Beta casomorphins are also exhibiting in typical synthetic formula used during development. BCM-7 and BCM-5, each are highest in colostrum or the first release of milk used immediately after conclusion of gestation, followed by typical gradual decrease of BCM-5 and BCM-7 as development of post gestational physiology advances.

BCM-7 diminishes systemic adaptive neurological development processes for structure and function in the mature brain while, instead, promoting astrocyte exhibition and advancing differentiation of astrocytes at the cellular level. BCM-7 from Human breast milk experimentally promoted neurogenesis among neural stem cellular entities while also promoting the redox status and epigenetic changes linked to neural development, although breast milk is known to cause hyperpotentiation in astrocytes and neural cellular entities that opens a field which produces a synapse between maternal cognition, maternal physiology, maternal neural capacitance and developing post gestational cognition, physiology and neural capacitance. This hyperpotentiation enables epigenetic influence to be exchanged between maternal physiology and post gestational physiology.

Studies o A2 milk consumption presented improved consistency and frequency of excretory output among the A2 groups compared to A1 groups, with inconclusive differences in cytokines although the cytokines used may not have been as focused as those found to be most useful in this compendium of research. Similarly, cytokines, digestive pathway output function, each are complicated by exposure to EMF and RF.

Lactose intolerant symptoms were statistically significant in indicating a beneficial, preventative and alleviating effect resultant of A2 milk consumption.

Anticasein immunoglobulin activity have the highest levels in diabetes mellitus, suggesting that A1 milk may prime the immunological system to exacerbate autoimmunological activity which promotes system nonresolution cytokine activity that promotes susceptibility to disease.

BMC-7 can stimulate mucin enzyme production of mucin to protect digestive pathways.

A2 milk variants are linked with lower adipose factor percentages in produced milk compared to A1 which have higher percentages of fat.

Casein Kinase II or CK2 is linked to cellular cycle progression, suppression of apoptosis, circadian rhythm activation, DNA repair, and exhibition in particular viral budding apparatuses that link CK2 to susceptibility to particular viral vectors. Silmitasertib is an efficient inhibitor of CK2.

Information) “The global phosphorylation landscape.” ‘Cellular.’ Volume 182. Number 3. Pages 685 to 712. Article e19. 2020.

Information) “Milk Quality.” Font Nutr. Volume 9. Article 842375. 2022.

Information. “Analysis of Beta Casein A1 and A2.” Website for Food and Health Research.

Information) “Trends on Milk Containing Only A2 beta-Casein.” Animals (Basel). Volume 12. Number 15. Page 1909. 8th Month, 2022.

Information) “A1/A2 Milk.” Food Technology Magazine. December 1, 2018.

Information) “Difference Between A2 Milk and Regular Milk.” Website. Medical Review Date, 10th month, 13th Day, 2021.

Information) “Casein Kinase II.” Encyclopedia of Signaling Molecules. ISBN 978-1-4614-6438-9

Information) “Protein Kinase.” Journal of Dairy Science. Volume 86. Issue 4. Pages 1147 to 1156. 4th Month, 2003.

Sirt2 is described in the literature as being as being dissociated from DBC1 or prevented from being integrated with DBC1 by CK2 phosphorylation of the ESA domain which results in increased interaction with ESA domain with the central catalytic domain of Sirt2.

Information) “Regulation of Sirtuin Function by Posttranslational Modification.” Frontiers in Pharmacology. Volume 3. Article 29. Page 29. 2nd Month, 2012.

Sirt5 deacetylates pyruvate dehydrogenase complexes and deacetylates succinate dehydrogenase complexes, resulting in upregulation of the production of their substrate or their products correlated with balance of NADH compared to NAD+. Sirt3 and sirt7, thus, can activate succinate dehydrogenase. Succinate promotes the transsulfuration pathway through which methylene bridge cysteine is structurally deteriorated. The condition ALS, in one of its versions, is characterized by upregulated transsulfuration activity or translation of glucose into succinate, contrasting with the typically beneficial effect of depleting methylene bridge cysteine. Succinate becomes fumarate through succinate dehydrogenase. Sirt3 and Sirt7 also both interact with phases of the cellular respiration pathway. SIRT5 and generally among sirtuins, nicotinamide performs as an inhibitor of deacetylation by receiving acyl groups from sirtuins in a way that conforms the role in PARP production of nicotinamide during signaling in which it removes ribose from NAD+ to distribute ribose to local substrate to cause a gradient upon which material and nucleotides for DNA repair might be recruited. Arginine adjacent to the nicotinamide pocket in sirt5, as an example or as a subgroup of Sirtuins, interacts with succinate to cause sirtuins or Sirt5 to become desuccinylases.

The literature suggests that any of these substrates for the Krebs cycle can be added and then can upregulate or start the Krebs cycle.

Importantly, the literature is inconsistent in presenting the role of Rub P carboxylase or rubisco in its shunting of ribulose metabolites into the glycolysis to enhance, upregulated or start glycolysis at the juncture between pyruvate and the Krebs Cycle, along with the shunting or ribulose into the Krebs cycle directly, upregulated, enhancing or staring the Krebs cycle. The debate is not the function of rubisco in carbon fixation into biology but, instead, the debate is if rubisco exists in Human physiology, particularly because rubisco was included in the Human genome databanks until recently when it has been obscurely presented in this context. Rubisco is the most abundant enzyme in the biome and it was a participant in the great oxygenic event which resulted in enhanced availability of oxygen and is linked to the ability of organisms to increase in size. The current biome exhibits inadequate exhibition of CO2 for rubisco to fully exhibit its catalytic potential in carbon fixation into biology, such that Rubisco is diminished its translation of CO2 into biology, which debunks theories about the biomes ability to support life. Biomass thus, from a rubisco perspective, removes CO2 from the atmosphere and produces enhanced substrate for Life while Human PEMT function is a strong detoxification pathway for the atmosphere through atmospheric respiration and PEMT. THMT, INMT, methylthioglycolic acid catalytic structural deterioration of oncology potentiating factors and ability of these pathway metabolites to be instrumented to clean industrial wastes.

Neuromelanin is known to interact in electromagnetic spectrum and extraelectromagnetic spectrums of field and influence to produce balance and coordination, while impaired neuromelanin is linked disease with impaired movement and coordination and while early development exhibits incomplete coordination in correlation with developing, enhancing and increasing levels of neuromelanin in the Suprachiasmatic Nucleus.

Rubisco may benefit biology by providing substrate that can be shunted into multiple entry points into the Krebs cycle.

The Krebs cycle is known to be omitted during anaerobic glycolysis, greatly downregulating biosynthesis of numerous factors including proteins that are well known in physiology. Its omitting is strong reason why energy molecule output decreases from about 32 molecules per cycle to about 9 to 6 molecules per cycle.

Aerobic glycolysis occurs when PEMT continues to be downregulated, P53 continues to be increasingly potentiated or increasingly expressed, while energy metabolisms increase above 9 to 6 energy molecules per cycle, resulting in imbalanced translation of mined hydride from structure and membranes into circulation and metabolism. Aerobic glycolysis is beneficial when PEMT is active and functional because PEMT exhibits diverse genomic and metabolic stability mechanisms, PEMT integrates methyl groups into cellular membranes and phospholipids to regulate growth/development/homeostasis, PEMT integrates resolution phase stabilizing fatty acids at enhanced focus rates into cellular membranes and structure, and PEMT2 in particular emerges near birth to impose systemic and structural regulation that can even require 1 to 1 ration of methyl groups with catalytic, metabolic, growth and development factors.

PEMT downregulations invokes systemic involvement at enhanced levels to maintain homeostatic, and these systemic capabilities become targets of disease, pathology promoting factors, and other vectors of risk, including deterioration of brain, conditioning, lucidy, cognitive capacitance, and integration of the less than conscious and conscious mind in regulation of physiology and in regulation of how physiology interacts with environment to the benefit self, group, species, Life, biome and the universes.

The literature observes that sirtuins generally integrate with NAD, particularly as NAD+ and this integration is in the sirtuin C pocket which promotes alkylimidate formation and nicotinamide release. Nicotinamide, after release, can reintegrate in the C pocket and depotentiate or inhibit deacetylase activity sirtuins that have already released nicotinamide. The sirt5 desuccinylation catalytic potential is downregulated by nicotinamide, presented in the literature as being enabled to deactivate desuccinylation through a sirt5 specific arginine that is able to ascertain distal carboxylate substrates. GW5074 specifically abrogates sirt5 desuccinylation while allowing sirt5 to exhibit deacetylase activity. Thus, the C pocket can have isoform specific characteristics that can occupied, changed, drugged, modulated otherwise, downregulated by inhibitors, upregulated or otherwise used to impose isoform specific regulation. These suggest that a system including redox factors is superimposed on basal physiology, perhaps suggesting that the systems represented in physiology are layered upon one another, providing increasing benefit, and perhaps providing benefit that is specific to changes in environment.

Sirt6 exhibits deacetylase, adp-ribosyltransferase, and defattyacylase activity.

Desuccinylation is has been experimental observed in with sirt5, sirt3, sirt7 and sirt4.

Generally, desuccinylation activity is different when differentiation occurs while diacylation is consistent with differentiation.

General cellular lysate catalytic rates for desuccinylation were observed to be biphasic, changing after initial rates of desuccinylation.

Proliferating muscle and adipose tissue exhibited increased levels of desuccinylation activity but do not exhibit increased deacetylase activity in experimental conditions.

Cellular entities that are proliferation exhibit reprogramming toward desuccinylation by sirt that increases sirt desuccinylation but does not upregulated deacetylation. The literature observes nicotinamide integrate as counteractively downregulating a particular sirt proteins performance of deacetylation but did not observe a specific downregulation of deacetylation during proliferation that exhibits upregulated desuccinylation. These suggest that cellular lysate performance of deacetylation can occur independently of the bolted-on catalysis of sirtuins. The systems seem to be layered. Generally, nicotinamide downregulates sirt deacetylase activity.

Cellular lysate desuccinylases activity can likewise use NAD+, other than sirt performance of desuccinylases activities using NAD+.

Information) “Sirtuin Activators and Inhibitors.” Pharmacol Ther. Volume 188. Pages 140 to 154. 8th Month, 2018.

Information) “Desuccinylase.” Scientific Reports. Volume 10. Article number 17030. 2020.

Desuccinylation levels for cellular level lysates were 10 times lower than NAD+ linked desuccinylation, revealing how obscure different in redox enabled transactions and transactions without assisted energetics may be different in volume.

Downregulation of nucleotide availability, canonical anaerobic glycolysis or PARP depletion of NAD+ directs pyruvate and NADH from glycolysis toward lactate and NAD+. Resultant of ribose removal from NAD+ by PARP, persistently because of inadequate nucleotides caused by downregulated pentose phosphate pathway enabled production of 5 carbon sugars for nucleotide and NADPH synthesis, and the occurrence of DNA repair invoking of persistent PARP signaling in a million or more instances each day in each cellular entity, it is able to be concluded that nicotinamide is available enough to downregulate sirt deacetylase activity generally.

Generally, sirt deacetylase activity is downregulated in canonical anerobic glycolysis that occurs when PEMT is downregulated. This downregulation of deacetylase activity can occur with de facto upregulation of desuccinylases activity when the sirt involved are sirt5, sirt3, sirt7 and sirt4.

Uniprot presents Human SIRT5 as a demalonylase, desuccinylases and deglutarylase which is able to remove malonyl groups, glutaryl groups and succinyl group from proteins. Sirt5 regulates circulatory fluid ammonia levels particularly during fasting. Sirt5 actives CPS1. Sirt5enables desuccinylation and deglutarylation of CPS1. Sirt1 frees CPS1 to increase catalytic activity by CPS1. CPS1 catalytic activation occurs correlative to NAD+ availability. Superoxide Dismutase 1 or SOD1 is activated bySirt5 desuccinylation, disrupting reactive oxygen species, but promoting the reactive oxygen mediation cascade from superoxide to H2O2 requiring catalase and peroxiredoxins or vitamins and n acetyl l cysteine. H2O2 can become peroxynitrite when involving Nitric Oxide Synthase uncoupling. Catalase diminishes H202 particularly but is deactivated by upregulated methylene bridge cysteine.

Sirt5 enables SHMT2 activation through desuccinylation. SIRT2 desuccinylates HMGCS2 to activate HMGCS2 and activate ketogenesis.

Sirt5 has minimal deacetylase activity although it can deacetylate cytochrome c cycs, uox and other proteins.

The specific catalysis of sirt5 for desuccinylation includes H2O, N6-usccinyl-L-lysyl-[protein] + NAD+ translation by sirt5 bidirectionally into 2’-O-succinyl-ADP-D-Ribose, l-lysyl-[protein], and nicotinamide. Glutaryl proteins and malonyl proteins can be substituted for succinyl in this reaction to constitute their respective catalytic patterns performed by sirt5.

The literature observes remarkable and even extreme duration of vital being in correlation of metabolic characteristics that include depletion of methylene bridge cysteine through the nonrecycling pathway known as the transsulfuration pathway. Interestingly aerobic conditions required exhibition of improved redox capable proteins including lysine, phenylalanine, cysteine, tryptophan, tyrosine and selenocysteine, all of which counteract the debatable exhibition of anaerobic glycolysis as a homeostatic status particularly because anaerobic glycolysis occurs when PEMT is most active and particularly because anaerobic glycolysis includes lactate increase, NAD+ increase and PARP signaling persistence that result in increased required activity by systemic buffering systems, organs and tissues. It is interesting how the upregulation of lactate and persistent depletion of NAD+ could have reasonable been regarded as homeostatic status.

Sulfur exhibiting amino acids, cysteine and methionine, both of which perform as components of buffering systems, and can become impaired or deactivated when used by buffering systems to manage ph and homeostasis, are both correlated with extreme duration of being in Animalia. Duration of being is linked to decreased methionine in Animalia, although it not clear if this decrease is because upregulated metabolisms of methionine by PEMT, other methyltransferases and transsulfuration depletion of methionine production by recycling pathways, or if this correlation is the result of methionine nutritional decreases. A study observed nutritional decreases in methionine as vector of enhanced duration of being, although the clinical data differentiates methionine direction toward methylene bridge cysteine by PEMT as being harmless compared to other pathways that produce methylene bridge cysteine from methionine.

Methionine is a primary substrate and indicator of production of methylene bridge cysteine, while oxidative distress is lower in contexts of extreme duration of being, while lower levels of sulfur exhibiting amino acids seems circumstantial, although the great oxygenic event which downregulated atmospheric ratio of sulfur compared to oxygen seems relevant in adaptive replacement of reactive oxygen counteractance compared to focus on reactive sulfur counteractance management. Observations regarding sulfur and oxygen exposure differences during phases of hibernation and no hibernation are revealing in this regard. Hibernation may result in decreased oxygen utilization and increased exposure to enclosed areas where sulfur may have an opportunity to increase in ratio compared to oxygen.

Methionine can be translated into s-adenosyl methionine followed by s-adenosyl methionine becoming s-adenosyl methylene bridge cysteine, while subsequently s-adenosyl methylene bridge cysteine can become methylene bridge cysteine through the activity s-adenosyl methylene bridge cysteine, s-adenosyl methylene bridge cysteine can become s-adenosyl methionine through the activity of INMT, and s-adenosyl methylene bridge cysteine might also be regulated by proteolysis or autophagy. Methylene bridge cysteine can then be recycled by THMT according to sulfur availability and thetin substrate availability into methylthioglycolic acid, representing another pathway of methionine bereft producing nonrecycling pathway for methylene bridge cysteine. Methylene bridge cysteine might also become methionine through B12 and 5 methyltetrahydrofolate and methionine synthase activity, BHMT2 and s-methylmethionine sulfonium activity, betaine/n,n,n glycine betaine/trimethylglycine and BHMT activity, and other pathways that may not be clearly elucidated in the literature.

The transsulfuration pathway is interesting because it results in nonrecycled methylene bridge cysteine metabolism. Methyltransferases are pervasively used to detoxify hormones, toxins, toxic metals, xenobiotics, histamine increases, and other factors, all resulting in a sequester CH3 from s-adenosyl methionine which becomes methylene bridge cysteine known to be a radical involved in all disease, diminished behavior and correlated in serum um/L with aging and detrimental nuances of aging. A study of centenarians observed that at about 80 years, increases in abated vital being correlated with age, abate, the sigmoid graph flattens, and metabolic characteristics of the most aged included perturbed B12 levels and increased levels of methionine. Extreme aging may involve stabilization of these two parameters, but certainly involves management of methylene bridge cysteine or practices that are interventional at habitual and clinical levels. Methylene bridge cysteine reflect toxicity exposure, xenobiotic exposure, allergen exposure, increase in toxic metabolites, cytokines which downregulated PEMT to cause de facto upregulation of methylene bridge cysteine because PEMT recycles methylene bridge cysteine into itself but promotes flux and tagging of homocysteine to prevent it from participating in detrimental toxic pathways.

However, methylene bridge cysteine deactivates biologically active molecules by enabling polymerization linked to pathology, sequestering the hydride from biological active molecules, deteriorating atom level interactions and adhesions that are functional within biology, causes upregulation of free fibrin, occupies fibronectin to cause deposits in cardiomyocytes, agrin, and other tissues, as well as deactivates catalase, and is able to produce almost every symptom observed in disease without aspects of disease being exhibited otherwise. An analysis in this compendium of research found 3 or more, single-spaced pages of detrimental factors caused by methylene bridge cysteine in only a limited, cursory consideration of these potentialities. An objective review of methylene bridge cysteine, including a search on the internet for virtually any diminished outcome whatsoever, pervasively reveals a correlation to levels of methylene bridge cysteine, also revealing that diminished neurological basis of social behavior, all beginning with brain deterioration from methyl group and choline inadequacy beginning at gestation, clearly presents that human misfortune and diminished outcomes are centered upon allowed exhibition of the effects of upregulated methylene bridge cysteine.

Since 1878 the ability to downregulated methylene bridge cysteine is characterized in the clinical literature, suggest that methylene bridge cysteine has been allowed to flourish because it generates massive opportunity to benefit from the diminished outcomes of Human populations. The omitted opportunities of antecedent eras are now being supplanted by the limitless opportunity of imputing Human priority in such contexts in a way that allows Human advancement to what is next in the continuation of the Human experience.

The transsulfuration pathway directs methylene bridge cysteine to cystathionine and cysteine, generally including vitamin B6 as a cofactor.

Extreme duration of being is correlated with methylene bridge cysteine becoming cystathionine, followed by directing of cystathionine toward succinyl-CoA of the Krebs/citric acid cycle, or directing of cystathionine toward cysteine then either glutathione or taurine although it is known that cysteine can become cystine, H2S, HS, sulfate, methanethiol and other metabolites.

It should be observed that glutathione, zinc and other factors are used to detoxify the production of dimethylthetin by BHMT and BHMT2 to prevent dimethylthetin from downregulating BHMT and BHMT2.

Desuccinylation by sirt5, sirt3, sirt7 and sirt4 supplies succinate which can be shunted directly into the Krebs cycle where succinate potentiates fumarate, fumarate potentiates malate, malates potentiates oxaloacetate although oxaloacetate is also produce as a possible metabolites of pyruvate when PEMT/P53 are functional and all pyruvate is not being directed toward lactate, oxaloacetate becomes citrate correlative to pyruvate being directed toward acetyl-CoA/CO2 when all pyruvate is not being directed toward lactate, citrate becomes isocitrate, isocitrate becomes alpha-ketoglutarate although arginine/glutamine/proline/histidine all become alpha-ketoglutarate, followed synthesis of succinyl-CoA although, again, Acetyl-CoA is downregulated when pyruvate is directed to other outcomes such as phosphoenolpyruvate, alanine, acetaldehyde and ethanol, Acetyl-CoA toward Citrate and CoA, and oxaloacetate.

Thus, succinate provides two loci for insertion into the Krebs cycle as succinyl-CoA and sugar exhibiting succinate in a way that enables the Krebs cycle to potentiate directing of cystathionine into the Krebs cycle, thereby promoting substrate cycling through the transsulfuration pathway. Succinate is known otherwise to potentiate the transsulfuration pathway.

Succinyl-CoA Synthetase bidirectionally performs catalytic interconversion of ATP, CoA and Succinate with ADP, phosphate and succinyl-CoA.

Heretofore, these analyses have not made observations regarding the role phosphorylation and phosphorylation cascades. Thus, it is now important to observe that phosphorylation of molecules introduces molecules into participation in the intracellular pKa balance, allowing more molecules to participate in determining cellular pKa or extending pKa homeostatic balancing interactions to molecules which were not included before phosphorylation.

Succinyl-CoA is a precursor to cystathionine and heme.

Succinyl-CoA enables entry and exit of proteins from the pKa balancing and homeostatic oscillation.

Experimental microbial observation of aerobic conditions reveals a 1000 percent increase in production of succinyl-CoA when succinate is the substrate compared to when glucose is the substrate for biosynthesis.

The following study observes metabolic and enzyme factors that are correlated with and in some instances explain extreme duration of being.

Information) “Methionine Transsulfuration Pathway is Upregulated in long-‘living’ Humans.” Volume 162. Pages 38 to 52. January 2021.

Information) “Succinyl-CoA Synthetase.” The Enzymes. Volume 10. Pages 581 to 606. 1974.

Uniprot. Q9P2R7. Succinate-CoA Ligase. ATP – Specific Succinyl-CoA Synthetase.

Information) “Differential Sensitivities.” PLoS ONE. Volume 7. Number 9. E45098. 2012.

Information) “Sirt5.” ‘Mol ‘Cellular Entity.’ Volume 50. Number 6. Pages 919 to 930. 6th Month, 2013.

Information) “Transsufluration.” Neurobiol Dis. Volume 144. 105025. 10th Month, 2020.

Information) “Sirtuin 3 Deacetylase Activity.” PLoS One. Volume 6. Number 8. E23295. 2011.

Information) “Sirt3.” Front Pharmacol. Volume 13. 871560. 2022.

Information) “Nicotinamide.” PLoS One. Volume 7. Number 9. E45098. September 2012.

The succinate dehydrogenase enzyme or succinate - coenzyme Q reductase or respiratory complex is exhibited in the inner mitochondrial membrane and participates in both the electron transport pathway and the citric acid cycle.

Managing methylene bridge cysteine toward 3.7 um/L or lower may be a therapeutic objective to alleviate effect to the strong ion gap or strong ion balance.

The literature observes that pyruvate is converted to acetyl-CoA during aerobic conditions and pyruvate is converted into lactate within anaerobic conditions, while it is known P53 downregulates pentose phosphate pathway and downregulates glycolysis from about 32 energy molecule synthesis per cycle to about between 9 and 6 molecules of ATP synthesis per cycle, resulting in canonical exhibition of anaerobic glycolysis. Anaerobic glycolysis causes competition of diminished pyruvate which is strongly potentiated as pyruvate and NADH toward lactate anion and NAD+ because of PARP signaling except in active muscle tissue and except in nonconditioned muscle tissue. Lactate dehydrogenase performs the translation of pyruvate and NADH into lactate anion and NAD+.

Information) "Bag 3." Autophagy. Volume 10, Number 9. Pages 1603 to 1621. September 1, 2014.

Information) "Bag 3." 'Cellular Entities.' Volume 9, Number 3, Page 574. 3rd Month, 2020.

Information) "Anti-Aging." Clin Interv Aging. Volume 15. Pages 387 to 393. 2020.

Information) "DBC1." US Patent Number US20090036375A1

Oral instrumentation of NAM diminished both sirt1 and sirt2 diminishes tau protein, upregulates autophagy in cerebral cortex and hippocampus, and improved cognitive function in experimental models of alzheimer’s. It is important to consider that Sirt1 decreases in aging and sirt2 increases in aging, typically. Sirt1 increase by resveratrol, SRT1720, and SRT1460 upregulate sirt1 and counteract the exhibition of misfolded proteins which are an impetus for upregulated proteolysis and activation of the unfolded protein response. The trihydroxy rsv causes overexpression of sirt1 and hyperactivates deacetylation of P53 by sirt1, and enables cellular survival by increasing sirt1, pgc-1a and ampk. The enhanced survival in this instance may be an opposite effect to oncological therapy, although sometimes it is the apoptosis inclination that results in the survival response that becomes or has become dysregulated in oncology. Trihydroxy rsv dissociates sirt1 from dbc1 and downregulates cytokines IL1b and tnf. Piceatannol was more potent than the trihydroxy rsv and intricate analysis revealed that the d that a sirt1 coumarin domain, produced by an extremity domain shared among all sirt isoforms, was integral to the therapeutic effect.

Coumarins, turmeric, curcumin a, including esculetin, imperatorin and other derivatives, are emerging as antivirals and have the ability to inhibit SP1, iNOS/NOS2 and AP1 which are central cytokines in pervasive diseases and conditions. It is either difficult or not possible to find a viral vector that affects homo sapiens detrimentally which is not prevented, intervened, eradicated or therapeutically affected by inhibitors of AP1, SP1, or iNOS/NOS2, while factors such as Berberine, curcumin, turmeric, coumarin, coumadin, irinotecan, berberine, esculetin, imperatorin, burdock/moringa/hovenia may repress these cytokines and diverse array of other cytokines.

Furanocoumarins, found in citrus fruits, umbelliferous vegetables and herbal medicines such as psoralen used photodynamic therapy, have recently been expanded to include bergamottin, dimeric analogs of bergamottin, the bergamottin isomer imperatorin (lemon oil, lime oils, and Angelica Dahurica, parsnips, fennel and parsley), and the imperatorin heraclenin are potent antineoplastic agents and potent downregulators of nonresolution cytokines, such that studies clearly observe that PMA, TAT protein, and other pathways of viral replication , were prevented and disrupted with pharmacological potent IC50 and area under the curve analyses by imperatorin in a way that include modulation of SP1, AP1, Cyclin D1, activated t cellular nucleus factor, NF kB and other cytokines. Hydroxy bergapten from Heracleum dissectum root and hernian along with coumarin from lavender, also are potent and useful coumarins.

Information) "Imperatorin." Mechanisms of Signal Transduction. Volume 279. Issue 36. Pages 37349 to 37359. September, 2004.

Information) “Heracleum.” Nat Prod Res. Volume 36. Number 13. Pages 3241 to 3246. July, 2022.

Information) “Biosynthesis of Coumarin and Herniarin in Lavender.” Science. Volume 137. Number 3534. Page 977 to 978. 9th Month, 21st Day, 1962.

Numerous modulators of SIRT1 and SIRT2 are presented in this peer reviewed journal article.

Information) “SIRT1 and SIRT2.” Front Pharmacol. Volume 11. Number 12. 1st Month, 2021.

Esculetin, derivatized as Esculetin 6,7 2hydroxycoumarin from plantae Artemisia capillaris, euphorbia lathyris, and citrus limonia potentially downregulates SP1 and has a therapeutic affect to oncology of leukocyte monocytes, oral oncology, and the most detrimental of dermal oncology.

Information) "Esculetin." Journal of 'Oncology' Prevention. Volume 20. Number 2. Pages 106 to 112. 6th Month, 2016.

Information) "Coumarin, An Emerging Antiviral Agent." Heliyon. Volume 6. Number 1. e03217. 1st Month, 2020.

Moringa Oliefera, hovenia, burdock, green, black and some other factors, as supplements or teas, along with olive oil and sweetened with diverse hexose sugars can be remarkably effective in preventing or alleviating discomfort, managing mood, alleviating behavioral challenges, and improving focus and stability. These can help begin a focused implementation of the recommendations presented in this analysis.

The path from incipient disease to advanced disease may typically have latency, in which a duration of advancing disease, division or proliferation of impaired cellular entities, and increasingly massive depletion of energy and membrane integrated energy factors, hydridic effect, might emerge. Persistent exhibition these conditions, observable as increasing levels of methylene bridge cysteine from accumulation of level of impairment from one factor or accumulation of increasing numbers of factors in this regard, are among typical modalities of emerged disease, advanced disease and diminishment of the neurological basis of social behavior. Often, also, behavioral components can be recruited to participate in advancement of disease, having the same empirical causal nuances of diminished behavioral outcomes.

Particularly, however, is the emergence in these contexts of upregulated SP1, a downregulator of PEMT, AP1 which is a downregulator of PEMT, iNOS/NOS2 which is a downregulator of PEMT, uncoupled iNOS/NOS2 which impair biological molecules/enzymes/structure directly and methylene bridge cysteine (hcy) which also impairs molecules/enzymes/structure directly, although methylene bridge cysteine can sequester the hydridic character of the 80,000 or more biological molecules that can carry NAD+/NADH or hydride. Hydridic exchange is the basis of metabolism and livingness in physiology, while membrane integrated hydride along with hydridic redox are essential to maintaining the 7.2 to 7.6 ph, 7.35 to 7.45 ph and 7.4 pH typically required for optimal consciousness and cognitive capacitance, with the mitochondrial potentials being strong controlling nuances of such capacitance with hundreds of mitochondria being exhibited in some cellular entities.

SP1 increase in copy number results in overexpression of telomerase which maintains the telomere sequences between genes and chromosomes that are required to be exhibited in order that Poly ADP Ribosyl attachment using a primer sequence of repeating nucleotides. Telomere-enriched regions can harbor cloverleaf structures known as G Quadruplexes which can exhibit cytokines in each of the 4 cloverleaf aspects of its structure. SP1 is a major cytokine in this context such that when the G Quadruplex becomes destabilized, an SP1 gene is exposed, followed by potential transactivation of SP1. SP1 upregulates telomerase, sustaining telomeric regions where SP1 copies can be harbored and made obscure. However, SP1 downregulates CD4+ and CD8+ receptor exhibition in lipid rafts on the outer aspect of outer plasma membrane. MHC histocompatibility complex presentation of intracellular monitoring complexes in CD4+ and CD8+ is thereby impaired, preventing complements and adaptive immunological synapses, along with monitoring by cytotoxic T cellular entities and monitoring by B cellular entities, all to become diminished.

Likewise, SP1 also upregulates PD1 and PDL1 which causes impaired or diseased cellular entities and lineages of impaired proliferating cellular entities. all to become obscured from T - Cellular entities, B - Cellular entities and other cellular, humoral, adaptive, innate or complements immunological systems. These are major components of latent disease although iNOS/NOS2 can become uncoupled and since it already has Calmodulin with its four Ca2+ loci, integrated into the iNOS/NOS2 structure, a resultant insensitivity to Ca2+ availability and L-arginine availability can result in uncoupled iNOS/NOS2 and depletion of these metabolites to cause eNOS and nNOS to also become disabled or exhibit uncoupled catalytic function, culminating in constriction of the caveolae. The caveolae are bends in the cellular membrane at which much of cellular signal transduction, lipid raft, and interactions with external environment can occur. Although transmembrane proteins or gap junction proteins exhibit interactions with other cellular entities, the caveolae constriction represents a major isolation of tissues from concerted control by physiology and isolating groups of cellular entities from systemic development control. Caveolae can be constricted and dilated. This full stack view of essential interactivity for optimal physiology is often impaired in disease, particularly latent disease.

An important interactive nuance in this context includes the function of AP1. AP1 is activated, like SP1, and like iNOS/NOS2 in pervasive disease, although much of microbial factors invoke these cytokines, including all viruses requiring not only iNOS/NOS2, but some viruses requiring uncoupled iNOS/NOS2 for latent disease and latent transactivation. AP1 upregulates telomerase, potentiating a rapid depletion of telomeres among diseased or impaired cellular entities, resulting in fusion of chromosomes and impaired ability of disease tissues to proliferate. SP1 counteracts AP1 by upregulating telomerase, resulting in a disruption susceptible, treatable, druggable and assayable canonical and essential context of latent disease of microbial and nonmicrobial versions. The literature observes that Berberine inhibition of AP1 and an AP1 downregulation therapy, curcumin inhibition of SP1 and an SP1 downregulation therapeutic, Active Hexose Correlated Compound and a choline kinase inhibitor, can thwart latent disease, latent viral disease, and oncology emerged in this context efficiently, although extended duration therapy can be required for eradication microbes and oncology.

Oncology relies upon efficient import of choline using sodium coupled choline transporters in an environment in which PEMT is downregulated to direct choline to the cdp-choline pathway and a nonresolution phase promoting pathway when upregulated over typical levels. Oncology relies also upon persistent nonresolution phase signaling, which also includes upregulation of S1P lyase as a major resistance pathway that becomes more prominent when the 26s/20S/19s proteosomes are inhibited because S1P lyase allows oncology or impaired cellular entities to escape phosphatidylinositol enabled autophagy from destabilizing oncology genotypes and phenotypes.

Importantly, the canonical context of disease and oncology are activation of nonresolution "somes" such as immunosomes and proteosomes, enhanced exhibition of downregulated PEMT which results in diminished density of Phosphatidylcholine and resolution phase fatty acids in cellular membranes, all along with upregulated exhibition of free hydrides and hydride carriers, along with DBC1 occupation of sirt1 and sirt2, resulting in free hydrides that promote cellular cycle progression. however, when cyclins and cyclin kinases including Retinoblastoma Protein pRb statuses depotentiate progression of cellular cycle, differentiation can occur which can be beneficial or promote pathology if the differentiation does not conclude with senescence, chromosomal fusion to prevent proliferation, each of which can include the function of AP1.

SP1 counteracts this process of clinical selection for cellular senescence. Importantly, the canonical conditions for persistent, advancing disease include diminished density of cellular membrane hydride, CH3 and phospholipids which is typically accompanied by increased exhibition of dysregulated energy including free hydride, free NADH factors and canonical warburg conditions in which increased throughout of glycolytic metabolisms above 6 or 9 molecules of ATP per cycle, increased exhibition of ATP integration into free choline by choline kinase to produce phosphocholine upregulation, and either counteracting of P53. The typical ratio of NAD+ to NADH which is 3 to 1, to 10 to 1, and in some instances 700 to 1, is disrupted when these aspects of impaired cellular function are counteracted.

A most important omitted factor in this context includes the requirement of only 1 or No prevalent aspects of cellular entities per micrometer to exhibited impaired metabolism in this regard because cellular entity to cellular entity interactions and exchange occur through gap junction proteins, resulting in exchange of impaired enzymes, upregulation nonresolution cytokines, and impairing metabolites such as phosphocholine and methylene bridge cysteine. A study of gap junction protein disruption has been presented as a modality of enhancing diverse therapies which involve modulation of cellular status, proliferation, apoptosis and stability.

Information. "Gap Junction Proteins." Advanced Materials. Volume 35. Issue 22. Article Number 2210464. 6th month, 1st day, 2023.

Disease, particularly oncology, interestingly, relies also upon detoxification of selenium, particularly by the enzyme selenophosphate synthetase 2 or SEPHS2. SEPHS2 is utilized to provide metabolites that result in production glutathione and peroxiredoxin which become defense mechanisms for oncology cellular entities. Correlatively, selenide is detoxified by SEPH2, while selenium in the version of selenides are toxic to oncology. Se-methylselenocysteine impairs this detoxification pathway and destabilizes oncology in a somewhat inclusive context. Some oncology versions are selenophylic although this is counteracted by selenocysteine produced by SEPHS2. Downregulating or ablating the function of SEPHS2 along with providing se - methylselenocysteine provides a powerful therapy that splinters oncology phenotypes into smaller focused therapies if resistant versions continued to be exhibited during selenide therapy. Inhibiting or modulating any enzyme, pathway or metabolite mentioned in this document should result in abatement of oncology pathology.

The SLC7AII enabled selenium endocytosis, selenocysteine synthesis, GPX4 synthesis and GPX4 synthesis, escaping ferroptosis, although this produces a reliance upon SEPHS2 to detoxify the highly toxic exhibition of selenide. Impairing selenide detoxification through therapeutic downregulation of SEPHS2 and providing Se - Methylselenocysteine to post enzymically downregulate throughput of SEPHS2, prevents oncological escape, although selenide, selenomethionine, and se-methylselenocysteine are presented in the literature as therapeutic when applied together as group of three factors. Other data suggests that Sodium should be included, such that these three selenium factors should be Na2SeO3, L-selenomethionine as C5H11NO2Se, and se-methylselenocysteine. Selenobetaine also results in exhibition 2methylselenide and trimethylselenonium. Selenocystamine also produces antineoplastic effects.

Information) “Comparison of Selenium and Sulfur Analogs in ‘Oncology’ Prevention.” ‘Oncology Promotion.’ Volume. 13. Number 7. Pages 1167 to 1170. 7th Month, 1992.

The SLC7AII symporter is another sodium coupled symporter and links, interactively, Sodium Coupled symporters for Iodide and Sodium coupled transporters for choline.

Information. "Selenium Detoxification is 'Essential' for 'Oncology Exhibition and Sustainment'." Nature Metabolism. Volume 2. Pages 603 to 611. Volume 2020.

The literature observes that oncology presents increased metabolic rate and oxygenic potentials, which involved redox exchange between thiols, oxygen and selenide including selenide and monomethyselenol, integrating, clearly, thiols, oxygen and reactive oxygen species, along with selenium metabolism.

Correlatively, therapeutic use of selenium is presented as requiring Selenium, selenomethionine and Se-methylselenocysteine, all, together. Again, Sodium Selenite as Na2SeO3, L-selenomethionine as C5H11NO2Se, and se-methylselenocysteine are essential in preventing oncology at low doses and at high dosages are highly toxic to emerged oncology. The exact doses for diverse oncology are presented in the following clinical, peer-reviewed journal article.

Information) "Selenium stimulates the Anti'neoplasticity' Immunity. Insights into Future Research." European Journal of 'Oncology.' Volume 155. Pages 256 to 267. 2021.

This compendium of research found an important link between sunlight exposure, selenium levels in soils and environment in some regions and the genotype of diary used in some regions, such that Selenium levels in some regions along with inadequate levels of exposure light from the sun were linked with susceptibilities to particular diseases, modulated by the phenotype of dairy products. A2 milk and dairy are closer to Human milk phenotype and result in decreased levels of phosphorylation cascade linked to nonresolution cytokine signaling, reproductive dysfunction, endometriosis, diminished behavior and diminished control, all which are linked to nonA2 milk obtainment. Selenium levels in soil can counteract both non A2 dairy and inadequate light from the Sun, while the modality of such counteractance is presented in this visualization.

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