A Cancer Therapy By Max Gerson - Selected Parts

[Travis]

I must be eating quite a bit of fibre; but like "saturated fat," it's a category that I never pay much attention to—I even like seeing it in the red (i.e. 500% RDA).

The similar thing can be said about iron, where I regard values under 100% as actually a good thing.

I see veganism as convenient, and I've been doing it for about ten years minus a few winters of heavy cheese eating and the occasional egg-eating. I find that it actually saves time eating raw food because you don't have to spend any time cooking.

These young kale leaves that I eat aren't too fibrous, and I just eat them raw (unless if they get kinda limp towards the end of the week from storage; then I steam). It sounds from your description that gorillas almost eat plants willy-nilly, selecting such things as bark, stems, and mature leaves—certainly quite the task. Them, and pandas (i.e. ), probably live symbiotically with some more esoteric bacteria in their digestive tracts—ones with β-galacotose-cleaving enzymes.

Starch gives me an opportunity for doing one of my favorite activities—bitching about biochemistry textbooks. Lehninger's fourth edition presents a chain of amylose in the Hawthorne Projection:

• Nelson, David L., Albert L. Lehninger, and Michael M. Cox. Lehninger principles of biochemistry. 4th edition.

Not especially illuminating, as these pyranose rings are not actually flat. Not having any double-bonds, these must exist in the chair configuration—maintaining the tetrahedral 109° bond angles seen in unsaturated chains. What follows is a more realistic representation of amylose:

click here for full image

And two amylose chains together actually form a double-helix:

• Hancock, Robert D., and Bryon J. Tarbet. "The other double helix—the fascinating chemistry of starch." J. Chem. Educ 77.8 (2000): 988.

Cellulose is an isomer of amylose, and nearly identical. The only difference is that the glycosidic ether bonds are connected to the rings in the axial configuration, the β configuration. This lends extra stability as now intramolecular hydrogen bonding can add additional strength, adding so many additional kilojoules per mole for maximum stability (H-bonds are depicted as dotted lines in following image):

click here for full image

Amylose's connectivity is α(1⟶4), and cellulose's connectivity is β(1→4). Each amylose glucose unit is superimposable in the image further above; and so is each other cellulose glucose unit.. Perhaps the most obvious difference is that each adjacent glucose unit in cellulose chain is rotated 180° about it's axis, thereby allowing each #3 carbon to hydrogen bond with each #4 pyranose (cycloether) oxygen. This does not happen in the amylose alpha chain.

We often don't have the enzymes to tear these β-bonds apart. This is sometimes stressed by the paleo crowd, and even the Western A. Price Foundation who—as it must be stated—also recommend consuming a β-glycosidic bond, a different one . . . in the form of lactose (β-D-galactopyranosyl-(1→4)-D-glucose).

The protein in leaves appear to be assimilated as well as . . . say, the protein in nuts? (I think so, perhaps Ray Peat can point-us in the right direction. From his article on milk:

• "The chemist Norman Pirie argued convincingly that leaf protein had much higher nutritional value than grain and bean proteins, and that it had the potential to be much more efficient economically, if it could be separated from the less desirable components of leaves." —Ray Peat

So to estimate the resistant fiber content, I think cellulose would be a good thing to look at (and also lignin). I tried to find a study showing how cellulose changes with time, as the leaf grows, but this doesn't appear to be a main consideration of any scientist. I'm sure the information is out there, somewhere—perhaps buried under a title you'd never have thought it would contain.

This one here shows about ⅓ as much sugar as cellulose in leaves, with lignin and cellulose nearly equal:

• Curran, Paul J., Jennifer L. Dungan, and David L. Peterson. "Estimating the foliar biochemical concentration of leaves with reflectance spectrometry: testing the Kokaly and Clark methodologies." Remote Sensing of Environment 76.3 (2001): 349-359.

So yeah, it's official: Leaves are a downright terrible source of energy (but a good source of minerals and a few select vitamins.)

I'm basically eating the free sucrose in pineapple, dates, apples, and pears this week; with some more fat and protein coming from whole coconuts and raw hydrated almonds. The kale is just there for the minerals, amino acids, carotenes, and folate. The leaf has manganese and calcium crystals in photosystem II, a fascinating enzyme which captures photons and [black box of speculation and intrigue] electrons to glucose while evolving O₂ in the process. (The veritable Chuck Norris of enzymes.) The calcium is necessary for thee oxygen evolving complex subunit of this enzymes, so leafs are actually impossible to find without Ca²⁺ since they cannot transduce energy without it.

• McEvoy, James P., and Gary W. Brudvig. "Water-splitting chemistry of photosystem II." Chemical reviews 106.11 (2006): 4455-448
• 
  
  • "Calcium was found in the 1980s to be an essential cofactor in oxygen evolution. One calcium is required per OEC [oxygen-evolving complex]. The metal’s proximity to the Mn₄ unit was established with the discovery that its binding depends on the S-state and of a long-lived, modified EPR [electron paramagnetic resonance] multiline signal produced by the S2-state of the Ca²⁺-depleted OEC. XAS [X-ray absorption spectroscopy] and pulsed EPR evidence for the location of Ca²⁺ within the OEC is detailed in section. It has been hypothesized both that calcium acts in water splitting by binding a substrate water molecule and that it modifies the redox potential of the OEC, perhaps by controlling proton transfer. Direct evidence for the former hypothesis comes from mass spectroscopic measurements of ¹⁸O-labeled dioxygen release from OECs in which calcium has been replaced with strontium. A review of calcium’s role in the OEC has recently been published." ―McEvoy

 

[Amazoniac]

Interesting. What about their high contents of nitrates, with studies showing beet juice raising NO and athletes using it as doping agent for that reason??

And I highly recommend this one:
Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy

--
Trimethylglycine aka Betaine Sets the Anabolic Stage for Increased Muscle Growth: Higher IGF-1 & Lower Cortisol - Statistically Significant, but Physiologically (Ir-)Relevant? - SuppVersity: Nutrition and Exercise Science for Everyone

You might find both interesting. The NO issue is discussed briefly at the end of the second link.

 

[Travis]

You might find both interesting. The NO issue is discussed briefly at the end of the second link.

I'll certainly look into that. I felt very cracked-out a few weeks ago after eating vegetables I had bought from the Amish—included high-nitrate cabbage and beets (especially beets.) Also, during that time, I had experimented with drinking a few Red Bulls™—something in which has additional niacin, a vitamin which can apparently effect people in different ways depending on their methylation status and tryptophan intake.

I tried to find some interesting info on nitrates, but nothing that I had found revealed any significant biological effects. But I had a thought just yesterday that I was going to look into that again, something I need to do anyway since NO is involved in vascularization (while always keeping in mind how methylglyoxal reacts with arginine, of course.)

 

[haidut]

You might find both interesting. The NO issue is discussed briefly at the end of the second link.

Right, so it says beet root juice raises NO due to the nitrates but betaine by itself does not.

 

[Wagner83]

I'll certainly look into that. I felt very cracked-out a few weeks ago after eating vegetables I had bought from the Amish—included high-nitrate cabbage and beets (especially beets.) Also, during that time, I had experimented with drinking a few Red Bulls™—something in which has additional niacin, a vitamin which can apparently effect people in different ways depending on their methylation status and tryptophan intake.

I tried to find some interesting info on nitrates, but nothing that I had found revealed any significant biological effects. But I had a thought just yesterday that I was going to look into that again, something I need to do anyway since NO is involved in vascularization (while always keeping in mind how methylglyoxal reacts with arginine, of course.)

Beets and aragula reliably increased NO imo, aragula was even more potent, I saw the effects on erection, asthma, allergies.

 

[Amazoniac]

So you have that, a situation in which calcium can be seen both as a cancerostatic and as a carcinogen.

http://www.mgwater.com/seelig_magnesium_and_trace_substance.pdf

 

[Travis]

http://www.mgwater.com/seelig_magnesium_and_trace_substance.pdf

Well, apparently Dr. Andre Barbeau think that calcium—and magnesium—cause Parkinson's.

• Barbeau, André, et al. "Ecogenetics of Parkinson's disease: prevalence and environmental aspects in rural areas." Canadian journal of neurological sciences 14.1 (1987): 36-41.
• • "On the other hand, studies of small regions have often yielded information on the presence of focal environmental risk factors responsible for some forms of parkinsonism; for example manganese in miners and industrial workers,⁽⁶⁾⁽⁷⁾ the concentration of calcium and magnesium in drinking water on the Island of Guam⁽⁸⁾⁽⁹⁾ or well water in rural south-eastern Saskatchewan." ―Barbeau

He seems confused, since all of the early researchers stressed the aluminum and manganese content—and especially the aluminum content. If he wants to make a case for calcium, he needs to explain the low Parkinson's rates among dairy farmers. He also has to explain why such high levels of aluminum were always found in the nerves of Guam ALS patients—by such methods as: neutron activation,

• Yoshimasu, Fumio, et al. "Studies on Amyotrophic Lateral Sclerosis by Neutron Activation Analysis‐2. Comparative Study of Analytical Results on Guam PD, Japanese ALS and Alzheimer Disease Cases." Psychiatry and Clinical Neurosciences 34.1 (1980): 75-82.

laser microprobe mass spectrometry,

• Kasarskis, Edward J., et al. "Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study." Journal of the neurological sciences 130.2 (1995): 203-208.

electron dispersive spectroscopy,

• Garruto, Ralph M., et al. "Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam." Proceedings of the National Academy of Sciences 81.6 (1984): 1875-1879.
• Perl, Daniel P., and Arnold R. Brody. "Alzheimer's disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons." Science 208.4441 (1980): 297-299.

morin, and solochrome azurine stains.

• Piccardo, P., et al. "Histochemical and X-ray microanalytical localization of aluminum in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam." Acta neuropathologica 77.1 (1988): 1-4.

He really seems confused; it's actually low calcium that does it (coupled with high-aluminum, of course.)

• Garruto, R. M., et al. "Low-calcium, high-aluminum diet-induced motor neuron pathology in cynomolgus monkeys." Acta neuropathologica 78.2 (1989): 210-219.

Calcium cannot produce neurofibrillary tangles, but aluminum can (it's the only thing that can actually do this)

• Hof, Patrick R., et al. "Neurofibrillary tangle distribution in the cerebral cortex of parkinsonism-dementia cases from Guam: differences with Alzheimer's disease." Brain research 564.2 (1991): 306-313.

And people drink high . . . excuse me—low calcium water all of the time without developing Parkinson's! Distilled water has never been shown to be a risk factor.

• Perl, Daniel P., et al. "Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam." Science 217.4564 (1982): 1053-1055.
• 
  
  • "Comparatively high levels of aluminum and unusually low levels of calcium and magnesium have been found in samples of drinking water and garden soils from Guam and two other high incidence foci of ALS and PD, one in the Kii Peninsula of Japan and the other in southern West New Guinea." —Perl and Gadjusek
• • 
    
  • "On the other hand, studies of small regions have often yielded information on the presence of focal environmental risk factors responsible for some forms of parkinsonism; for example manganese in miners and industrial workers, the concentration of calcium and magnesium in drinking water on the Island of Guam [?] or well water in rural south-eastern Saskatchewan." ―Barbeau

But perhaps his originally draft was stealth-edited by the The Canadian Journal of Neurological Sciences?

There's always that possibility . . .

 

[Travis]

Beets and aragula reliably increased NO imo, aragula was even more potent, I saw the effects on erection, asthma, allergies.

I used to buy arugula, and even eat a pound per day at times. This was different. I think it was probably the niacin with low methyl pool. The foods that I eat are relatively-low in methionine, so I think I was on the lower end of the methyl scale. I feel slower after the almonds, but not sure if that's from the methylation or from the linoleic acid.

I was thinking more about eicosanoids and how they have that reactive epoxide group. This could have been an early device to kill cellular invaders—a defensive molecule produced when the cell membrane lipids are disrupted.

It seems as though all molecules have a primary function before they—or their derivatives— become signalling molecules, during evolution. Pregnenolone and progesterone are the two main components of myelin, and have the natural shape to form around microtubules (inner nerves). The nuclear progesterone receptor would have come later, as the cell would need nerves first to have much use for it.

The androgens aren't that far removed from cholesterol ⟶ pregnenolone ⟶ progesterone, and are involved in nerve growth as well. This signals the sex differentiation stage of evolution.

Then came mineralcorticoids: then glucocorticoids.

Plants make a product similar to some eicosanoids, as a defense measure. These are called phyto-oxolipins, and they're made from linoleic acid.

• Blée, Elizabeth. "Impact of phyto-oxylipins in plant defense." Trends in plant science 7.7 (2002): 315-322.

click to embiggen

Thromboxane A₂ is an epoxide, and prostaglandin G₂ has both hydroperoxy and cycloperoxy groups. These are involved in inflammation signalling, and the highly-reactive oxygen groups could have originally been created as a cellular defense measure against bacteria.

 

[Amazoniac]

Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra
Worth reading. He writes about "U" shaped curves yet Travisord doesn't care about them. He's into "T" shapes since he doesn't tolerate imperfections. It's all or nothing.

​

 

[Amazoniac]

https://raypeatforum.com/community/...anscribed-verified-and-reposted-4-12-14.5334/
Rayzord talking about niacin/niacinamide and how sirtuins expression is related to stress.

 

[Amazoniac]

https://www.researchgate.net/profil...3a7d3f4/CANCER-Why-tumours-eat-tryptophan.pdf

"There is mounting evidence that fast-growing 'progressive' cancers occur because of a failure of the immune system to maintain control over budding tumours. The ability of cancers to escape immune responses is therefore attracting increasing attention, with numerous studies now pointing, perhaps surprisingly, to the consumption of the amino acid tryptophan as a critical factor in progressive cancer. On page 197 of this issue, Noonecares at al.[1] advance the field with their finding that many cancers upregulate a liver enzyme, tryptophan dioxygenase, to drive tryptophan consumption. What’s more, the authors find that the primary product of this process, kynurenine, is an endogenous ligand for the aryl hydrocarbon receptor, which mediates invasive tumour growth. This second finding links the fields of toxicology, immunology and cancer biology in new ways, and may help to explain how elevated tryptophan consumption helps tumours to overcome immune barriers to cancer progression."​

 

[Travis]

https://www.researchgate.net/profil...3a7d3f4/CANCER-Why-tumours-eat-tryptophan.pdf

"There is mounting evidence that fast-growing 'progressive' cancers occur because of a failure of the immune system to maintain control over budding tumours. The ability of cancers to escape immune responses is therefore attracting increasing attention, with numerous studies now pointing, perhaps surprisingly, to the consumption of the amino acid tryptophan as a critical factor in progressive cancer. On page 197 of this issue, Noonecares at al.[1] advance the field with their finding that many cancers upregulate a liver enzyme, tryptophan dioxygenase, to drive tryptophan consumption. What’s more, the authors find that the primary product of this process, kynurenine, is an endogenous ligand for the aryl hydrocarbon receptor, which mediates invasive tumour growth. This second finding links the fields of toxicology, immunology and cancer biology in new ways, and may help to explain how elevated tryptophan consumption helps tumours to overcome immune barriers to cancer progression."​

That's fascinating; but if true, they should change its name to the kyneurenine receptor. No receptor should be named after it's unnatural ligand.

Ray Peat mentions that tryptophan is the only amino acid shown to be carcinogenic. I think that he's right. Methionine causes growth, but this did not translate to cancer in the four rat studies that I'd read (but Koch will tell you that amines are carcinogenic, and I think he's correct. The methionine rat studies were of short duration.)

I had previously just ascribed the carcinogenic activity of tryptophan on its ability to raise growth hormone. Most people on this forum are aware of the fact that brain dopamine impinging on the pituitary suppresses the release of prolactin; less people are aware that prolactin's relative and evolutionary precursor—growth hormone—is synthesized in proportion to brain serotonin. Prolactin, if I remember correctly, activates phospholipase C on the cell membrane. This results in a release of inositol phosphates from the membrane phospholipids leading to a calcium spike. Microtubule scientists have also determined that Ca²⁺ concentrations of 1·μM can depolymerize microtubles. Nanomole prolactin concentrations can induce an intracellular Ca²⁺ spike of this magnitude. Since a complete breakdown of the cytoskeleton is necessary for mitosis, one is tempted to believe that prolactin contributes to mitosis partly in this manner (and perhaps through the other product of phosphilipase C, a diglyceride that could produce an unusual lipid hormone similar to eicosanoids. Has a di-eicosanoid ever been isolated?)

Perhaps we should find out what growth hormone does? What are it's second messengers?

 

[Amazoniac]

CokI mean, Koch in "The chemistry of natural immunity":

Note while reading how nutrients directly involved in oxidation are usually unsaturated in nature or have to be transformed in such way to propagate reactions. We have to stop giving untasurated compounds a bad cottonation from trauma of PUFA.
It's possible to realize from it why Gersòn didn't allow blenders to be used, there's too much agitation/aeration for these delicate compounds to remain intact.

"It is known that in hepatectomized animal fructose is not used by the tissues, and glucose is used. Yet glycogen is split by the liver to fructose di-phosphate which is directly usable by the issues. Fructose is not used as such and fructose di-phosphate is not known to circulate in the blood. Howeva the white blood cells that have much to do in carrying material after a meal may manufacture or may well convey some precious fructose phosphate compound from the liver to the working cells where it is liberated under conditions of tissue activity. This consideration permits that a dehydrated hexose molecule be burned for energy production, and a demand upon white cells which may call them into hyperplasia when their work is handicapped. Thus we have employed a large dehydrated fructose phosphate and glucose phosphate molecule and their fully unsaturated derivatives in the leukemias, coronary thrombosis, hypogeorginism and cancer, and in the acute infections as poliomyelitis and in the chronic infections like tuberculosis and leprosy that excite a small round cell infiltration, with the most pleasing results. And since the deficiency involved is repaired by this procedure we believe our reasoning has been correct."
Zeus, I know you've adjusted the posture on your chair after this one.

"Vitamins A, B, B2, and D, Warburg's yellow pigment, ascorbic acid, cytochrome, adenylic acid, and the other co-enzymes must all be considered and made good wherever cell multiplication goes on beyond physiological control, or as we may say "allergically." However at the bottom of such conditions stands the toxic structure we will discuss later and this must be removed through a vigorous oxidation catalysis. It is even necessary to maintain the balance of mono-valent and di-valent cations necessary to correct the injury to dispersion of the cell colloids caused by physiological activity, such as happens in an extreme degree as a result to changes in complex substances in the development of tetany. Therefore, calcium, magnesium, and potassium are required in correct amounts in various oxidation systems, to maintain a water in lipod phase."

"The vitamins of the D series, sterols closely allied to cholesterol, have essential physiological activity. Their photochemic significance and relation to calcium retention without parathyroid aid gives their sterol structure still more importance. This is especially true since calcium is necessary to the sugar oxidation mechanism. Through a photochemic action the pro-vitamin, ergosterol, is changed to a three ring system having three sets of conjugated double bonds between carbon atoms. The A ring is ruptured at "C-9," and the hydroxyl is retained at "C-3." An unsaturated carbon linkage is present in the side chain. Photochemic activity is therefore marked. There is no proof that the vitamin is not changed in the tissues by oxidation either at the hydroxyl or in the side chain to resemble a sex hormone closely. The fact that only the structure with a free hydroxyl unprotected by an acetyl or glucoside union is active is significant in this direction. It is interesting too that the anti-rachitic and the calcium-fixing properties are separate, and the further products of irration of ergosterol, tachysterol, and toxysterol have no anti-rachitic properties like vitamin D, calciferol, although they are strong calcium fixing agents."

"The oxidation mechanism includes very definitely [] both vitamins B1 and B2. Vitamin B1 is a Thyol-pyrrol-pyrimidine derivative. Its molecule contains five unsaturated unions between carbon atoms. Its structure suggests possibility of being a pro-nucleic acid derivative, and its function is tied up with that of nervous system. Its deficiency causes beri-beri, a disease showing peripheral neuritis and paralysis, suppressed heart action, and diminished oxidation with lactic acid accumulation in the brain. Pyruvic acid accumulates in the blood, and brain tissue slices use less oxygen than normal brain slices. Addition of the vitamin to the slices immediately raises the oxidations to normal and its administration to animals showing deficiency immediately corrects the total pathology. Thus this vitamin is definitely an oxidation agent. It may function thus directly by virtue of its several unsaturated unions between carbon atoms and between carbon and nitrogen atoms. It possesses [thanks for the "Brain possessor" idea for the next quote] an amino group that can very easily be replaced by an oxygen atom thus producing a carbonyl group able to serve as an oxidation carrier. It may also serve the oxidation mechanism indirectly as a building unit for the production of nucleic acid.
B2 the anti-pellagra substance [1939 book] is probably a flavine derivative containing five double bonds and two carbonyl groups and pentose attached to a meso-nitrogen atom in nucleotide fashion. Thus it resembles Warburg's yellow pigment, a hydrogen acceptor in the presence of dehydrogenase co-enzyme. If the structure so far suggested is correct this body too functions in the oxidation mechanism, which its carbonyl groups may serve as carriers. [Thiamine was the first to be discovered, so it probably had much more literature on it back then. I suspect that Niacin wasn't discovered first because it's so important that there are many ways to conserve, generate or regenerate its NAD coenzyme]
Thus the vitamins fit into the body chemistry much like the hormones and may replace them in some respects, for instance, tachysterol parathyroid and suprarenal hormone are interchangeable in calcium fixing activity. Moreowaaaa, under natural living conditions where a man exercises and perspires in the sunlight, he manufactures his own ergosterol (which otherwise is only built up in fungi and fish), and he converts this substance into vitamin D, and its further calcium-fixing irradiation products. But excessive irradiation may contribute carcinogenic properties."

"Choline has much to do with the oxidation of fats. That it prevents the conversion of amino acids and of sugars to fats under the influence of cholesterol, it seems there is sufficient evidence when the rest of the oxidation mechanism is normal. It does not aid the burning of aceto-acetic acid [acetylsucholine], but where the rest of the oxidation mechanism is sound, its presence favors the burning of fats or their precursors by another route. It is, therefore, an important link in the oxidation mechanism, but of course where the oxidation process is otherwise impaired we must assume that it not only fails to function and therefore accumulates [again] or is formed in greater quantity for compensation than normally occurs; and worst of all it is not burned itself and produces its toxic effects. Thus one might well assume that it is a factor in coronary disease, much like cholesterol is in other vascular degeneration that are so well known. In fact they both accumulate where the normal catalysis of oxidation is broken, and therefore both coronary disease and atheromatous degeneration and arterial sclerosis depend upon one basic deficiency, a crippled oxidation catalysis [also known as hypotravisism]." "Vascular normalcy is important to tissue function and obliterative vascular disease so often the cause of tissue degeneration that one might say that all disease shows its marks on the vascular system early or late. The infectious granulomata all start out with an obliterative endarteritis. Cancer does also, and cancer should be classified with the granulomata. They are all based upon toxic activity that destroys oxidation catalysis. They are all curable by restoration of the oxidation catalysis to normal or to better than normal."
@Frankdee20

"Through an over-active nervous system, therefore, in the presence of deficient oxidation catalysis, an accumulation of metabolites to toxic concentration, be it sucholine, neurine, cholesterol or some other, is possible whereby disease is produced in a similar way to that caused by disease germ poisons where the oxidation catalysis is insufficient to destroy them. The various allergies including cancer possess in this way an additional mechanism for being brought about and being maintained. Again let me repeat that the restoration of a vigorous oxidation catalysis removes the offending substance, no matter what its origin may be, and thus establishes the basis for recovery."

"The oxidation mechanism is also influenced by the glands of internal secretion. They all play a part in conserving or stimulating fuel and oxygen usage in a variety of complicated ways which adapts their service perfectly to the most specifically differentiated requirements. For their best co-ordination they are placed under the control of the central nervous system. Under normal conditions this is a wise provision, but it lays the gland system open to allergic interference through the nervous system. Since they mutually antagonize or reinforce each other's activity, allergic hyperactivity of a part of the nerve center may excite or inhibit one or more gland activities and produce profound changes such as diabetes, toxic goitre, or any of the other well known or obscure endocrine disturbances. Fortunately allergic activity of nervous tissue (for example, as expressed by shingles, or even certain forms of mental imbalance and inhibited development) is readily corrected by the measures we propose farther along, and thus the most profound endocrine disease has yielded very promptly and permanently to this treatment. Such prompt response could only follow the correction of an allergic state for it takes place sooner than tissue regeneration of any gland could be accomplished. However, the nerve or the gland tissue development that follows the removal of oxidation inhibition has been observed to take place with remarkable speed; for instance, the descent and development of the testes in young adults, and the gain of normal painless menstruation cycles in young females, the restoration of thyroid and pituitary function, and the improvement in mentality of imbeciles and idiots [or definitely not Dave and Diokine]."

"It is known [] that gastric ulcer develops mostly in those who have suffered some form of nerve exhaustion or other change in the central nervous system. A mental or nervous influence is a factor in many allergic disturbances. Adjunct to the brain control, the pituitary exercises the hormone control over the other ductless glands, and allergic activity of any of its functions like allergy of any of the endocrines demonstrates characteristic disease."

"One must not forget the ease with which some aromatic hydroxyl compounds change to quinones, or even exist as both forms in equilibrium in solution and in the solid state. Since as we will describe, the quinone group can conduct chain reactions and liberate energy quite perpetually, and through its fluorescent properties this group is like other unsaturated unions between atoms and can appropriate exothermic energy evolved in its environment and either use it for activation of its own chemical processes, or hand the energy on to a suitable acceptor that can so use it, we have in these properties all that is necessary to make a virus of a suitably constructed molecule."

"Through irradiation by sunlight, X-rays or ultraviolet light or by chemical activity the production of double bonds and the shifting of those present to produce isomers not normally present, the normal oxidation and conducting functions we assign to cholesterol may well be lost to be replaced by catalytic peroxidation activities such as the terpenes carry on. Thus one molecule of altered cholesterol adsorbed in chromatin becomes the energy generator that is in position to force the chemistry of cell division of neoplasia. The cholesterol changed by irradiation and oxygen has also some opportunity to take on quinone structure and become a catalyst for energy production by the method to be described later, which energy in like manner must force cell division. Polymerization of unsaturated derivatives of cholesterol and from sugars offers a group of substances not yet known to exist but which must not be forgotten in cancer research, and the stigmasterol peroxides in ether extract of wheat germ oil showing carcinogenic behavior must be examined from that standpoint too."

"It might be argued that all substances that have to do with energy production and energy distribution are of sugar origin, though greatly modified, or carry sugar in their structures. Among them ascorbic acid deserves a word. It is definitely of sugar origin, derived by oxidation of two carbon atoms. The reduced form carries an unsaturated union between the second and third carbon atoms. The oxidized form carries a chain of three keto groups, two of them hydrated. It is able therefore to carry an oxidation chain reaction, and has definite photochemic properties. Since it is so easily destructible it is able to serve in a minor way in the immunity against infection and against cancer as described below, and the reason for the feebleness of ascorbic acid as compared with each of the various Ketenones we use for this purpose is observable on comparison. These reagents were put into use a quarter of a century ago. It is, therefore, a matter of greatest satisfaction that the chemistry of vitamin C, so recently contributed, is confirmatory to out thesis."

"The study of allergy and immunity as here presented proceeds on the basis of the established experience of physiochemistry and physiology with the aid of a working hypothesis and clinical observations. It identifies a defect in the oxidation catalysis as a fundamental feature in the causation of disase, without which secondary causes should not find support."

 

[Travis]

It's interesting that he talks about things that Szent-Györgyi and Pauling would later elaborate upon.

"It is interesting too that the anti-rachitic and the calcium-fixing properties are separate, and the further products of irration of ergosterol, tachysterol, and toxysterol have no anti-rachitic properties like vitamin D, calciferol, although they are strong calcium fixing agents." ―Koch​

I sometimes think about such things, as some molecules appear to have a simple function that only later becomes controlled through hormonal effects—effects mediated by the same molecule, as ligand. Take for example prostaglandins, whose similarity to plant phyto-defensins is undeniable. Cyclooxygenase appears to have evolved to produce the highly-reactive cycloperoxide group to destroy invaders (adding to arachidonic acid), but this is something that actually happens nonenzymatically (the isoprostanes). Indeed, some enzyme chemists never tire of pointing-out that most enzymes just speed-up the reactions that would otherwise occur anyway—albeit at a much slower rate. The PPAR nuclear receptors seem to have evolved for the purpose of sensing a disturbance of the cell membrane, as well as the efficacy of the defense (i.e. cycloperoxide groups left unreacted).

Similar things can be said about calcium affinity and inositol phosphates.

Thiamine, or vitamin B₁—a molecule which could have been a de-carboxylase even before an enzyme had evolved to accelerate that—has a few unusual properties:

"Addition of the vitamin to the slices immediately raises the oxidations to normal and its administration to animals showing deficiency immediately corrects the total pathology. Thus this vitamin is definitely an oxidation agent. It may function thus directly by virtue of its several unsaturated unions between carbon atoms and between carbon and nitrogen atoms. It possesses [thanks for the "Brain possessor" idea for the next quote] an amino group that can very easily be replaced by an oxygen atom thus producing a carbonyl group able to serve as an oxidation carrier. It may also serve the oxidation mechanism indirectly as a building unit for the production of nucleic acid." ―Koch ​

But no mention of the sulfur atom.. .

First there was Koch: Then there was Breslow—and then Knell!

"and the stigmasterol peroxides in ether extract of wheat germ oil showing carcinogenic behavior must be examined from that standpoint too." ―Koch​

I'm surprised that you didn't parenthetically-insert a remark after that comment?

"Vitamins A, B, B2, and D, Warburg's yellow pigment [...] Thus it resembles Warburg's yellow pigment, a hydrogen acceptor in the presence of dehydrogenase co-enzyme." ―Koch​

I love Warburg Yellow. This is my favorite color in by box of biochemical crayons (much better than bilirubin yellow, and great for coloring Big Bird!)

 

[Amazoniac]

I'm surprised that you didn't parenthetically-insert a remark after that comment?

I guess the vit E post that I tagged you primed me for it, so I wasn't shocked..

 

[Amazoniac]

Methyglyoxal is highly reactive, which makes it good as an.. ignitor but dangerous when sustained:

Lactate vs. CO2 in wounds, sickness, and aging; the other approach to cancer

In 1932, a pediatrician, Alexis Hartmann (with M. Senn) in St. Louis, injected intravenously a solution of sodium lactate into patients with metabolic acidosis, and several of them survived---despite the fact that some of them were already suffering from an excess of lactate. The subsequent widespread use of lactate solutions in hospitals has contributed to the general denial of its toxicity.

Hartmann and Senn used racemic lactate, that is, a mixture of D-lactate and L-lactate. Our own tissues produce mostly L-lactate, but they can produce small amounts of D-lactate; larger amounts are produced by diabetics. Intestinal bacteria can produce large amounts of it, and it has many toxic effects. Methylglyoxal can be formed from either form of lactate, and it is an important factor in the glycation of proteins. It can also be formed from MDA, a product of lipid peroxidation. Protein glycation is an important factor in diabetes and aging, but glucose, rather than lactate and polyunsaturated fats, is commonly said to be the cause.

http://raypeat.com/articles/articles/co2.shtml

A quick reduction of carbon dioxide caused by hyperventilation can provoke an epileptic seizure, and can increase muscle spasms and vascular leakiness, and (by releasing serotonin and histamine) contribute to inflammation and clotting disorders. On a slightly longer time scale, a reduction of carbon dioxide can increase the production of lactic acid, which is a promoter of inflammation and fibrosis. A prolonged decrease in carbon dioxide can increase the susceptibility of proteins to glycation (the addition of aldehydes, from polyunsaturated fat peroxidation or methylglyoxal from lactate metabolism, to amino groups), and a similar process is likely to contribute to the methylation of histones, a process that increases with aging. Histones regulate genetic activity.

 

[Travis]

Methyglyoxal is highly reactive, which makes it good as an.. ignitor but dangerous when sustained:

"Intestinal bacteria can produce large amounts of it, and it has many toxic effects. Methylglyoxal can be formed from either form of lactate, and it is an important factor in the glycation of proteins."​

And lactate can be formed from methylglyoxal—the definitive role of enzymes glyoxyalse I & II.

Throughout the '50s, '60s, and '70s, the powerful ability of methylglyoxal to reverse tumors became well-known. Beginning in the '80s, it started to be framed in a bad light—as a "glycating" agent. This isn't even precise terminology, as we're all aware that glucose has six carbons and methylglyoxal has but three.

What happens is that methylglyoxal adds to the arginine side-chains of proteins. This forms a cyclic imidizole compound very similar to histidine. Although generally framed as pathological, Paul Thornally has shown that this event controls transcription through modifying a nuclear transcription factor.

• Yao, Dachun, et al. "High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A." Journal of Biological Chemistry 282.42 (2007): 31038-31045.

. ..framing this event as a post-translational modification—perhaps as a way for the cell to sense the glycolysis rate. In fact, arginine is the most prevalent amino acid at the catalytic site of enzymes—tempting one to think that it controls metabolism through methyglyoxal, perhaps by making the catalytic site (un)responsive to its substrate. All other post-translational modifications are given proper consideration as such, and even some nonenzymatic ones are imbued with significance and consequence they probably don't even have (vide infra):

• Saiardi, Adolfo, et al. "[Spontaneous] Phosphorylation of proteins by inositol pyrophosphates." Science 306.5704 (2004): 2101-2105..

Methylglyoxal naturally exists in nanomolar concentrations within the cell, a concentration which normally rises after ingesting glucose. Methylglyoxal spontaneously adducts onto glutathione, where it's then shuttled through the enzymes glyoxyalse I & II forming lactate. Low methylglyoxal means high lactate: Could these two enzymes be the link between the Koch–Szent-Györgyi Effect and the Warburg Effect?

Besides modifying key cellular transcription factors and enzymes, methylglyoxal temporarily occupies glutathione. This is of course reversible, but high steady-state methylglyoxal levels are thought to control cell division in this manner as well. Glutathione in the cell nucleus is a prerequisite for cell division.

Polyamines in the cell nucleus are also a prerequisite, and methylglyoxal appears to interact with these as well. William Koch talks about this, and because methylglyoxal's ability to turn arginine into cyclic compounds is indisputable—though denigrated semantically by the moniker "glycation"—you could easily imagine how it could turn a polyamine into a large N-heterocycle.

Within the class of polyphenols, the cancer inhibitory effect (IC₅₀) of each molecule parelells it's ability to inhibit in vitro the enzyme glyoxylase I. I should mention—at the risk of "flogging a dead horse," so to speak—that the cancer proliferation IC₅₀'s among polyphenols do not correlate with their antioxidant capacities in any way, shape, or form.

Curcumin is different, because it has trouble penetrating the cell membrane. When considering only molecules of the same size, charge, and shape: you do see a good correlation.

Much higher levels of methylglyoxal than normal do not kill the cell, but effectively inhibit mitosis. This is reversible, and the cell will divide upon removal of methylglyoxal. All methylglyoxal formed withing the cell is: Converted into lactic acid through aforementioned enzymes; occupies glutathione—inhibiting division; adds to arginine side-chains thereby controlling transcription and perhaps even enzymatic activity; and can even be thought to mop-up polyamines by creating cyclic structures of them through aldehyde–amine additions.

Teleologically, I would think that this enzyme would act to throttle the flux between glycolysis and the electron transport chain–speeding up the oxidation of triose sugars when levels become too high and slowing when low. Something should be said about diabetes . . . to perhaps avoid confusion: Diabetics have high blood sugar; they don't necessarily have high intracellular sugar. You cannot see diabetes as a model for high methylgloxal levels anywhere besides in the blood, lymph, and urine.

• Szent-Györgyi, Albert. "The living state and cancer." Proceedings of the National Academy of Sciences 74.7 (1977): 2844-2847.

 

[Amazoniac]

And lactate can be formed from methylglyoxal—the definitive role of enzymes glyoxyalse I & II.

Throughout the '50s, '60s, and '70s, the powerful ability of methylglyoxal to reverse tumors became well-known. Beginning in the '80s, it started to be framed in a bad light—as a "glycating" agent. This isn't even precise terminology, as we're all aware that glucose has six carbons and methylglyoxal has but three.

What happens is that methylglyoxal adds to the arginine side-chains of proteins. This forms a cyclic imidizole compound very similar to histidine. Although generally framed as pathological, Paul Thornally has shown that this event controls transcription through modifying a nuclear transcription factor.

• Yao, Dachun, et al. "High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A." Journal of Biological Chemistry 282.42 (2007): 31038-31045.

. ..framing this event as a post-translational modification—perhaps as a way for the cell to sense the glycolysis rate. In fact, arginine is the most prevalent amino acid at the catalytic site of enzymes—tempting one to think that it controls metabolism through methyglyoxal, perhaps by making the catalytic site (un)responsive to its substrate. All other post-translational modifications are given proper consideration as such, and even some nonenzymatic ones are imbued with significance and consequence they probably don't even have (vide infra):

• Saiardi, Adolfo, et al. "[Spontaneous] Phosphorylation of proteins by inositol pyrophosphates." Science 306.5704 (2004): 2101-2105..

Methylglyoxal naturally exists in nanomolar concentrations within the cell, a concentration which normally rises after ingesting glucose. Methylglyoxal spontaneously adducts onto glutathione, where it's then shuttled through the enzymes glyoxyalse I & II forming lactate. Low methylglyoxal means high lactate: Could these two enzymes be the link between the Koch–Szent-Györgyi Effect and the Warburg Effect?

Besides modifying key cellular transcription factors and enzymes, methylglyoxal temporarily occupies glutathione. This is of course reversible, but high steady-state methylglyoxal levels are thought to control cell division in this manner as well. Glutathione in the cell nucleus is a prerequisite for cell division.

Polyamines in the cell nucleus are also a prerequisite, and methylglyoxal appears to interact with these as well. William Koch talks about this, and because methylglyoxal's ability to turn arginine into cyclic compounds is indisputable—though denigrated semantically by the moniker "glycation"—you could easily imagine how it could turn a polyamine into a large N-heterocycle.

Within the class of polyphenols, the cancer inhibitory effect (IC₅₀) of each molecule parelells it's ability to inhibit in vitro the enzyme glyoxylase I. I should mention—at the risk of "flogging a dead horse," so to speak—that the cancer proliferation IC₅₀'s among polyphenols do not correlate with their antioxidant capacities in any way, shape, or form.

Curcumin is different, because it has trouble penetrating the cell membrane. When considering only molecules of the same size, charge, and shape: you do see a good correlation.

Much higher levels of methylglyoxal than normal do not kill the cell, but effectively inhibit mitosis. This is reversible, and the cell will divide upon removal of methylglyoxal. All methylglyoxal formed withing the cell is: Converted into lactic acid through aforementioned enzymes; occupies glutathione—inhibiting division; adds to arginine side-chains thereby controlling transcription and perhaps even enzymatic activity; and can even be thought to mop-up polyamines by creating cyclic structures of them through aldehyde–amine additions.

Teleologically, I would think that this enzyme would act to throttle the flux between glycolysis and the electron transport chain–speeding up the oxidation of triose sugars when levels become too high and slowing when low. Something should be said about diabetes . . . to perhaps avoid confusion: Diabetics have high blood sugar; they don't necessarily have high intracellular sugar. You cannot see diabetes as a model for high methylgloxal levels anywhere besides in the blood, lymph, and urine.

• Szent-Györgyi, Albert. "The living state and cancer." Proceedings of the National Academy of Sciences 74.7 (1977): 2844-2847.

Interesting as always.
❥ "the MG, while harmless at a low concentration, becomes toxic when its concentration exceeds that of the SH-glutathione present.
This leaves but one way open to maintain a low MG concentration, and this is by continuous infusion. P. Conroy of the Biochemical Department of Brunel University is studying the effect of such intravenous infusion in mice, the technique of which is cumbrous and difficult. Whether the maintenance of a low MG concentration will arrest growth of cancer has to be shown. MG, being a physiological substance, does not kill cells. It is possible that a cancer cell may be killed simply by arresting its proliferation, but it is also possible that it may be killed by the lowering of the pH, due to the production of D-lactic acid. The vascularization of cancer being poor, the acid may accumulate to a toxic concentration. If a tissue, such as liver, is treated in a blender in Ringer's solution, and is incubated with MG, within minutes its proteins are denatured and precipitated isoelectrically by the acid formed, the glyoxalase having been activated by the blender treatment. It seems possible that the cancer cell can be made to commit suicide by means of its own active glyoxalase, if a low concentration of MG is maintained."

So it can be sustained as long as the cell is guarded.​

❥ "It seems not impossible that ways to the prevention of cancer may also be found by means of decreasing the electron donor/acceptor quotient." "ray peat rule them all"
__
❥ "[AGEs] stick to certain parts of protein molecules and it happens that carbon dioxide also has this spontaneous ability to attach to those same group, and if carbon dioxide is abundant, you can't get glycation because carbon dioxide is protecting that."
❥ "most of the things that are called glycation are really fat-breakdown products."

 

[Amazoniac]

the electron donor/acceptor

Travisord, I noticed that you write NADH:NAD instead of the opposite, and it makes sense in terms of sequence and how the reaction should proceed.
Got to tell you that I estimate you almost as much as pboy for your knowledge. Saying something like this around here is quite a statement.

 

[Travis]

__
❥ "[AGEs] stick to certain parts of protein molecules and it happens that carbon dioxide also has this spontaneous ability to attach to those same group, and if carbon dioxide is abundant, you can't get glycation because carbon dioxide is protecting that."

They can only be talking about arginine, which also has affinity for carbon dioxide. Look at the structure: The two partial positive amines appear suitable to chelate the two partial negative ketones of carbon dioxide O=C=O.

I was reading about this a long time ago, before methylglyoxal, and found a few articles that demonstrate this.

If arginine can sense both carbon dioxide and methylglyoxal, then it would be a prime candidate to sense and control the metabolic rate. I wonder of you would find arginine in the catalytic site of nearly all glycolytic and Kreb's Cycle enzymes?