Universal Test For Cancer Progression/Stage

[Wagner83]

Eating arugula is the worst thing you can do for No, add huge amounts of beets and you have quite the cocktail.

 

[Amazoniac]

Eating arugula is the worst thing you can do for No, add huge amounts of beets and you have quite the cocktail.

I'm not sure, not even one decent Google Scholar result for arugula and nobelium. Also its half-life is at most 1 hour (nobelium, not arugula).
But for real, the nitrate content would be brutal indeed.

 

[tca300]

Amazoniac, what's your diet like?

Air
And Choline

 

[Nighteyes]

Thanks for the details. But another important question would be - what is the nutritional value of kale compared to an egg? Can one live off just cooked kale and say coconut oil (or butter)? There was a famous news article making the rounds last year proclaiming a person can thrive on a diet of just potatoes and butter, if they also take a multivitamin to compensate for deficiencies this diet would induce. Btw, I wonder why nobody raised the issue of EFA deficiencies those people on the potato/butter diet undoubtedly experienced...Probably because it was not an issue at all and those people thrived, which would have exposed the EFA scam if the issue was discussed publicly.
So, mashed potatoes with MCT sounds like a good way to avoid most of the toxicities of other food while providing close to 100% SFA.

My only concern with potato juice and large amounts of potatoes in general is the solanine. I dont know if there has been any studies done on the solanine content of potato juice as opposed to mashed etc. It seems to me that the sheer amount of potatoes needed to make any considerable amount of juice would increase the potential solanine burden. Maybe it precipitates along with the starch when left in the fridge overnight? Drinking the pure potato juice without letting it settle sure is revolting after the first gulp or two.. palatability seems way low to me.

 

[haidut]

My only concern with potato juice and large amounts of potatoes in general is the solanine. I dont know if there has been any studies done on the solanine content of potato juice as opposed to mashed etc. It seems to me that the sheer amount of potatoes needed to make any considerable amount of juice would increase the potential solanine burden. Maybe it precipitates along with the starch when left in the fridge overnight? Drinking the pure potato juice without letting it settle sure is revolting after the first gulp or two.. palatability seems way low to me.

I think cooking destroys most of the solanine. To my knowledge Peat never recommended drinking raw potato juice. The cooked mashed potatoes (if peeled) probably do not have much solanine either. Otherwise we would have seen food poisoning cases from eating potatoes, given how toxic solanine is, especially in children.

 

[Nighteyes]

I think cooking destroys most of the solanine. To my knowledge Peat never recommended drinking raw potato juice. The cooked mashed potatoes (if peeled) probably do not have much solanine either. Otherwise we would have seen food poisoning cases from eating potatoes, given how toxic solanine is, especially in children.

https://pdfs.semanticscholar.org/97f0/fea1a857a4cadd1cfd41323d3c2632bfcf62.pdf

I believe amazoniac posted This recently about the breakdown of solanine and it is heat stable up to around 230-280 degrees celcius. Far below cooking temperatures.. but yeah I suppose more cases would show up if it was indeed a big problem. Some are probably more sensitive than others. As a main source of protein it might start to build up though (in various tissue - see reference). Vague symptoms might not be recognized for what they are....

 

[Makrosky]

Air
And Choline

Yeah he's a "breatharian"

 

[Wagner83]

I'm not sure, not even one decent Google Scholar result for arugula and nobelium. Also its half-life is at most 1 hour (nobelium, not arugula).
But for real, the nitrate content would be brutal indeed.

Tested and approved (awful allergies and asthma, bigger erections). Aragula fresh from mountains located in the South of Italia tastes extremly good though, like sauceless salad with a great sauce. Sometimes the body and the brain want to follow the recommendations of the taste buddies.

 

[Mito]

As far as lipids go: dairy, coconut, beef, chocolate, and fruit all seem good. But for some reason, this forum seems to ignore the substantial linoleic acid content of eggs.
If it is expressed per gram linoleic acid, I would think it would be quite embarrassing to the egg; but I think expressing vitamins and minerals per calorie is the most fair approach. We all eat different volumes and masses of foods, yet everyone eats a very similar amount of calories per body weight.

The cronometer can answer this question with the least amount of work (normalized to 1000‧Cal apiece):

View attachment 8065 View attachment 8066 click to embiggen: Vitamins: Kale on left and egg on right (1000‧Cal).
View attachment 8067 View attachment 8068 click to embiggen: Minerals: Kale on left and egg on right (1000‧Cal).
View attachment 8069 View attachment 8070 click to embiggen: Amino Acids: Kale on left and egg on right (1000‧Cal).
View attachment 8071 View attachment 8072 click to embiggen: Fatty Acids: Kale on left and egg on right (1000‧Cal).​

Not accounted for in cronometer, I think eggs have significantly more biotin, choline and betaine if you consider them important.

 

[Amazoniac]

Raypond Meat in his '100 years of cancer metabolism' lensternewt:

"There is still interest in his [Györgyizord] theory, for example "The anti-cancer effect of methylglyoxal is now well established in the literature" (Pal, et al., 2016), but that molecule can also be toxic, depending on the condition of the cell. When the cell is healthy, methylglyoxal will be just one of many factors being created in the right place at the right time. The more volatile molecule glyoxal was one of Koch's reagents."

"When cells are dangerously overstimulated, oxygen and glucose are depleted. In the absence of oxygen, or when the ability to use oxygen is blocked, glucose is converted to lactate, and when glucose is depleted, glutamine is converted to lactate. With a limited supply of oxygen but an unlimited supply of lactate, the cell's metabolic reactions are shifted toward a reduced, electron-rich, state. This state inhibits the oxidation of glucose by blocking the enzyme pyruvate dehydrogenase, supporting the formation of lactate. These are internal processes of stressed cells, that can be interrupted when the organism provides corrective factors to restore oxidation."

"In the first reactions to injury, the inflammatory changes activate enzymes that support undifferentiated growth. The active thyroid hormone, T3, is destroyed locally by a specific deiodinase, prostaglandins are produced by cyclooxygenase, estrogen by aromatase, and nitric oxide by its synthase. These enzymes are activated by chemical reduction of their disulfide groups, converting them to thiols, and can be inhibited by appropriate oxidants. In a healthy organism, those oxidants are available."

"With stress and aging, the body's equilibrium on average is less oxidized, and this affects the so-called antioxidants in food. Phenolic groups typically have estrogenic and antioxidant effects. Several of the polyphenols and flavonoids in plants, that are known to be protective against cancer, contain several hydroxyl groups and only one activated carbonyl, and can function as antioxidants and interact with "estrogen receptors." However, like vitamin C, they can be oxidized to produce arrays of multiple activated carbonyls, with strong electron withdrawing (oxidative) effects (Son, et al., 2010). Their interactions with the body's oxidative systems have hardly been studied, but fisetin and a few others are known to be pro-oxidants in the body."

"The fact that the inflammation-promoting enzymes, aromatase, cyclooxygenase, and nitric oxide synthase, which are inhibited by an oxidizing environment are also inhibited by aspirin, would strongly suggest that aspirin and salicylic acid are functioning as pro-oxidants."

"Inescapable cellular excitation shifts cells into the characteristic cancer-like metabolism, and various anesthetics (e.g., propofol, a general anesthetic, and lidocaine, a local anesthetic) have been found to reduce tumor proliferation and inflammation." "Opioids stimulate cancer growth and metastasis, but they are still often used. (Byrne, et al., 2016.)"​

__
http://www.traceelements.com/Docs/The Nutritional Relationships of Selenium.pdf
"Sulfur (S) protects from selenium toxicity."
__

Yeah he's a "breatharian"

Other than ☀, you're the only other member that has special character, however the artist in question captured the moment while you were sleeping: ☯

 

[Travis]

Raypond Meat in his '100 years of cancer metabolism' lensternewt:

"In the first reactions to injury, the inflammatory changes activate enzymes that support undifferentiated growth. The active thyroid hormone, T3, is destroyed locally by a specific deiodinase, prostaglandins are produced by cyclooxygenase, estrogen by aromatase, and nitric oxide by its synthase. These enzymes are activated by chemical reduction of their disulfide groups, converting them to thiols, and can be inhibited by appropriate oxidants. In a healthy organism, those oxidants are available."​

This is a fascinating and bold statement. If this were true, that would make redox balance a very important control mechanism in the cell. To test this claim, I decided to read a short article on aromatase structure:

Ghosh, Debashis. "Structural basis for androgen specificity and œstrogen synthesis in human aromatase." Nature (2009)​

'Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site.'
​

These quotes are suggestive, and dripping with innuendo. Listen to how he explains how steroids are given wine, and then delicately caressed by aromatose within its binding pocket—with James Brown music on the turntable!

'The hydrophobic residues and porphyrin rings of hæm pack tightly against the steroid backbone, forming a cavity complementary in shape to the bound steroid (Fig. 2a).'

' The side chains of residues Arg 115, Ile 133, Phe 134, Phe 221, Trp 224, Ala 306, Thr 310, Val 370, Val 373, Met 374 and Leu 477 make direct van der Waals contacts with the bound androstenedione.'

'Androstenedione binds with its β-face oriented towards the haem group and C19 4.0 Å from the Fe atom.'

'The combined surface creates a pocket that encloses the bound androstenedione snugly. The volume of the binding pocket is no more than 400 ų, considerably smaller than the volume of about 530 ų of the active sites in 3A4 (ref. 22) and 2D6 (ref. 23), the two drug/xenobiotic-metabolizing human P450s with highest sequence identities (14–18%) to human aromatase.'
​

Four hundred cubic angstroms; any larger a binding pocket they'd have to call it marsupialase!

Now: about those thiol groups Ray speaks of:

'Having seven cysteines in the reduced form, the bulk of aromatase probably resides in the reducing environment of the cytoplasm.'
​

No talk of a disulfide bridge inactivating this enzyme, and no talk of these thiols being spatially located in a way that would allow disulfide bridge formation upon oxidation. I can find no indication of this enzyme's activity being controlled through the making or breaking of disulfide bridges, but I can picture it as being redox active on account of its porphyrin ring. Imaging perhaps this giant porphyrin ring collecting electrons which eventually shifts to Fe³⁺ ⟶ forming ·Fe²⁺, which is the iron species required to bind O₂.

​

The molecular oxygen is though necessary to turn the androgen's methyl group into formic acid (see above). Although depicted as Fe³⁺ in the above graphic, this may not be entirely accurate. The only way to determine the reduction state in the center of heme is through electron spin resonance (ESR); and in the case of phenylalanine hydroxylase, the iron needs to be in the Fe²⁺ state to adsorb O₂. This experiment also shows how an enzyme can be redox active solely through its heme group:

Wallick, D. E. "Reductive activation of phenylalanine hydroxylase and its effect on the redox state of the non-heme iron." Biochemistry (1984)​

This enzyme uses the pterin ring as a cofactor, either tetrahydrobiopterin or 6-methyl-tetrahydropterin (used below).

'As with pterin-reduced phenylalanine hydroxylase, the protein locus of the added electron is the iron center. This was shown by titrating Phe-hydroxylase with dithionite [a sulfur molecule] in a system containing the ferrous iron chelator, O‐phenanthroline.' ―Wallick​

'In order to determine whether dithionite-reduced phenylalanine hydroxylase is sufficiently activated for catalysis, the cofactor-product coupling experiment was repeated with both phenylalanine hydroxylase, and dithionite-reduced enzyme. The results are depicted in Figure 7, with dithionite-reduced Phe-hydroxylase giving an averaged straight line at 0.93 Tyr/pterin, while Phe-hydroxylase, gave a curved plot of decreasing slope very similar to that expected from Figure 2.' ―Wallick​

'Therefore, Phe-hydroxylase [PAH] pre-reduced with one electron/PAH subunit can function catalytically without need to undergo any further reduction by pterin,' ―Wallick​

'Since the two-electron oxidation product of dithionite is sulfite, and sulfite is known to act as a two-electron-reducing agent itself (Dixon, 1971a), it was necessary to determine whether product sulfite was serving to further reduce PAH following dithionite reduction of the enzyme.' ―Wallick​

'This work shows that a prereduction of Phe-hydroxylase is effected immediately prior to the normal catalytic event. When purified Phe-hydroxylase is added to a reaction system containing phenylalanine, molecular oxygen, and reduced pterin cofactor, stopped-flow spectrophotometry indicates the presence of a pre-steady reduction of Phe-hydroxylase by a stoichiometric amount of pterin, followed by a steady-state catalytic production of tyrosine. It is particularly noteworthy that dithionite can replace pterin in the reduction step as evidenced by observation of the anticipated tight ESR coupling between pterin oxidation and tyrosine formation exhibited by dithionite-reduced Phe-hydroxylase. Thus, addition of only a single electron is necessary for this measure of Phe-hydroxylase activation;' ―Wallick​

'The activation of Phe-hydroxylase by prereduction leads to the immediate question as to the locus for the electron furnished by the reducing agent. Since the enzyme contains 1 Fe/subunit, it was essential to characterize the redox state of the iron by examining its spectral properties. The native enzyme displays a composite EPR spectrum, a portion of which has features at effective g values of 6.7 and 5.4 that are similar to, although broader than, features commonly observed in ferric, heme proteins. This spectrum appears to arise from catalytically active ferric iron in a high-spin, S = ⁵⁄₂, tetragonally distorted state whose integrated intensity closely corresponds to the relative specific activity of the Phe-hydroxylase sample. The other portion of the EPR spectrum, with features near g of 9 and 4.3, correlates in intensity with the fraction of catalytically inactive iron. The integrated intensity of the signals in both regions indicates that the iron in Phe-hydroxylase is EPR visible. The EPR signals at g values from 5 to 7 disappear when phenylalanine or pterin are added to the anaerobic enzyme. Since anaerobic incubation of the tetrahydropterin cofactor or phenylalanine with PAH does not result in redox chemistry (Lazarus et al., 1981; Kaufman & Fisher, 1974), the loss of EPR signals cannot furnish information on the prereduction activation (step 1).' ―Wallick

​

'The mechanism requires that the reduction of the Phe-hydroxylase occurs only once at the beginning of the reaction. During the tyrosine-producing event (step 2), the enzyme functions catalytically and requires no further steps to maintain its activity. The view that the Phe-hydroxylase reduction step is a side reaction not related to its catalytic function but serving simply to oxidize cofactor nonproductively may be rebutted by noting that (1) these data mandate the cessation of flux through step 1 after the enzyme is activated since a coupling ratio (tyrosine/pterin) of unity is observed at pterin levels > Phe-hydroxylase (Lazarus et al., 1981; Kaufman, 1971) and (2) our results plus those from pulse-chase experiments demand that unreduced Phe-hydroxylase is largely inactive [Table I1 (Marota & Shiman, 1984)].' ―Wallick
'Several other non-heme, non-iron-sulfur enzymes possess similar types of EPR signals. Protocatechuate 3,4-dioxygenase exhibits EPR signals with prominent g = 4.3 features in the resting enzyme and ones in the region g = 7-5 after addition of substrate (Que, 1980). Soybean lipoxygenase also exhibits multiple signals in the g = 8–5 region after it is treated with 1 mol of its peroxy product, but the resting enzyme is EPR silent (Slappendel et al., 1982).' ―Wallick
​

He could be talking about singlet oxygen. Oxygen is unique in that it exists in a triplet and a singlet form, and is hence ESR active. Singlet oxygen is blue and is formed in during lipid peroxidation (Kasha, 1970).

'This fact suggests that a reduced iron state, Fe(II)-PAH, trapped by oxygen with formation of an iron–oxygen intermediate, may precede the formation of the actual hydroxylating species. Enzyme-bound iron–oxygen complexes have been well documented, with cytochrome P-450 (Ullrich & Duppel, 1975; Orrenius & Ernster, 1974; White & Coon, 1980) serving as an especially pertinent example of an enzyme that catalyzes hydroxylation reactions via iron–oxygen chemistry. The fact that the prereduction step may be accomplished anaerobically with dithionite provides an approach to investigate oxygen binding to Fe(II)-PAH and subsequent intermediates for the hydroxylation reaction.' ―Wallick​

I think this article makes clear that any heme enzyme (i.e. P450s) can potentially be catalyzed by electrons, and thus are very likely redox active. I think this can occur based on the large area or the porphyrin ring, able to spread a delocalized electron across it's entire conjugated superstructure—the electron eventually collected by Fe³⁺ ⟶ forming ·Fe²⁺, with subsequent O₂ adsorption [:Ö–Ö–Fe²⁺] and further catalytic activity.

Perhaps Ray Peat means that these enzymes are originally activated by disulfide reduction? perhaps translated and synthesized in disulfide form only to be irreversibly activated by reduction later?

Michael Kasha. "Chemiluminescence arising from simultaneous transitions in pairs of singlet oxygen molecules." Journal of the American Chemical Society (1970)​

 

[Amazoniac]

This is a fascinating and bold statement. If this were true, that would make redox balance a very important control mechanism in the cell. To test this claim, I decided to read a short article on aromatase structure:

Ghosh, Debashis. "Structural basis for androgen specificity and œstrogen synthesis in human aromatase." Nature (2009)​

'Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site.'
​

These quotes are suggestive, and dripping with innuendo. Listen to how he explains how steroids are given wine, and then delicately caressed by aromatose within it's binding pocket—with James Brown music on the turntable!

'The hydrophobic residues and porphyrin rings of hæm pack tightly against the steroid backbone, forming a cavity complementary in shape to the bound steroid (Fig. 2a).'

' The side chains of residues Arg 115, Ile 133, Phe 134, Phe 221, Trp 224, Ala 306, Thr 310, Val 370, Val 373, Met 374 and Leu 477 make direct van der Waals contacts with the bound androstenedione.'

'Androstenedione binds with its β-face oriented towards the haem group and C19 4.0 Å from the Fe atom.'

'The combined surface creates a pocket that encloses the bound androstenedione snugly. The volume of the binding pocket is no more than 400 ų, considerably smaller than the volume of about 530 ų of the active sites in 3A4 (ref. 22) and 2D6 (ref. 23), the two drug/xenobiotic-metabolizing human P450s with highest sequence identities (14–18%) to human aromatase.'
​

Four hundred cubic angstroms; any larger a binding pocket they'd have to call it marsupialase!

Now: about those thiol groups Ray speaks of:

'Having seven cysteines in the reduced form, the bulk of aromatase probably resides in the reducing environment of the cytoplasm.'
​

No talk of a disulfide bridge inactivating this enzyme, and no talk of these thiols being spatially located in a way that would allow disulfide bridge formation upon oxidation. I can find no indication of this enzyme's activity being controlled through the making or breaking of disulfide bridges, but I can picture it as being redox active on account of its porphyrin ring. Imaging perhaps this giant porphyrin ring collecting electrons which eventually shifts to Fe³⁺ forming Fe²⁺, which is the iron species required to bind O₂.

View attachment 8094
​

The molecular oxygen is though necessary to turn the androgen's methyl group into formic acid (see above). Although depicted as Fe³⁺ in the above graphic, this may not be entirely accurate. The only way to determine the reduction state in the center of heme is through electron spin resonance (ESR); and in the case of phenylalanine hydroxylase, the iron needs to be in the Fe²⁺ state to adsorb O₂. This experiment also shows how an enzyme can be redox active solely through its heme group:

Wallick, D. E. "Reductive activation of phenylalanine hydroxylase and its effect on the redox state of the non-heme iron." Biochemistry (1984)​

This enzyme uses the pterin ring as a cofactor, either tetrahydrobiopterin or 6-methyl-tetrahydropterin (used below).

'As with pterin-reduced phenylalanine hydroxylase, the protein locus of the added electron is the iron center. This was shown by titrating Phe-hydroxylase with dithionite [a sulfur molecule] in a system containing the ferrous iron chelator, O‐phenanthroline.' ―Wallick​

'In order to determine whether dithionite-reduced phenylalanine hydroxylase is sufficiently activated for catalysis, the cofactor-product coupling experiment was repeated with both phenylalanine hydroxylase, and dithionite-reduced enzyme. The results are depicted in Figure 7, with dithionite-reduced Phe-hydroxylase giving an averaged straight line at 0.93 Tyr/pterin, while Phe-hydroxylase, gave a curved plot of decreasing slope very similar to that expected from Figure 2.' ―Wallick​

'Therefore, Phe-hydroxylase [PAH] pre-reduced with one electron/PAH subunit can function catalytically without need to undergo any further reduction by pterin,' ―Wallick​

'Since the two-electron oxidation product of dithionite is sulfite, and sulfite is known to act as a two-electron-reducing agent itself (Dixon, 1971a), it was necessary to determine whether product sulfite was serving to further reduce PAH following dithionite reduction of the enzyme.' ―Wallick​

'This work shows that a prereduction of Phe-hydroxylase is effected immediately prior to the normal catalytic event. When purified Phe-hydroxylase is added to a reaction system containing phenylalanine, molecular oxygen, and reduced pterin cofactor, stopped-flow spectrophotometry indicates the presence of a pre-steady reduction of Phe-hydroxylase by a stoichiometric amount of pterin, followed by a steady-state catalytic production of tyrosine. It is particularly noteworthy that dithionite can replace pterin in the reduction step as evidenced by observation of the anticipated tight ESR coupling between pterin oxidation and tyrosine formation exhibited by dithionite-reduced Phe-hydroxylase. Thus, addition of only a single electron is necessary for this measure of Phe-hydroxylase activation;' ―Wallick​

'The activation of Phe-hydroxylase by prereduction leads to the immediate question as to the locus for the electron furnished by the reducing agent. Since the enzyme contains 1 Fe/subunit, it was essential to characterize the redox state of the iron by examining its spectral properties. The native enzyme displays a composite EPR spectrum, a portion of which has features at effective g values of 6.7 and 5.4 that are similar to, although broader than, features commonly observed in ferric, heme proteins. This spectrum appears to arise from catalytically active ferric iron in a high-spin, S = ⁵⁄₂, tetragonally distorted state whose integrated intensity closely corresponds to the relative specific activity of the Phe-hydroxylase sample. The other portion of the EPR spectrum, with features near g of 9 and 4.3, correlates in intensity with the fraction of catalytically inactive iron. The integrated intensity of the signals in both regions indicates that the iron in Phe-hydroxylase is EPR visible. The EPR signals at g values from 5 to 7 disappear when phenylalanine or pterin are added to the anaerobic enzyme. Since anaerobic incubation of the tetrahydropterin cofactor or phenylalanine with PAH does not result in redox chemistry (Lazarus et al., 1981; Kaufman & Fisher, 1974), the loss of EPR signals cannot furnish information on the prereduction activation (step 1).' ―Wallick

View attachment 8095 ​

'The mechanism requires that the reduction of the Phe-hydroxylase occurs only once at the beginning of the reaction. During the tyrosine-producing event (step 2), the enzyme functions catalytically and requires no further steps to maintain its activity. The view that the Phe-hydroxylase reduction step is a side reaction not related to its catalytic function but serving simply to oxidize cofactor nonproductively may be rebutted by noting that (1) these data mandate the cessation of flux through step 1 after the enzyme is activated since a coupling ratio (tyrosine/pterin) of unity is observed at pterin levels > Phe-hydroxylase (Lazarus et al., 1981; Kaufman, 1971) and (2) our results plus those from pulse-chase experiments demand that unreduced Phe-hydroxylase is largely inactive [Table I1 (Marota & Shiman, 1984)].' ―Wallick
'Several other non-heme, non-iron-sulfur enzymes possess similar types of EPR signals. Protocatechuate 3,4-dioxygenase exhibits EPR signals with prominent g = 4.3 features in the resting enzyme and ones in the region g = 7-5 after addition of substrate (Que, 1980). Soybean lipoxygenase also exhibits multiple signals in the g = 8–5 region after it is treated with 1 mol of its peroxy product, but the resting enzyme is EPR silent (Slappendel et al., 1982).' ―Wallick
​

He could be talking about singlet oxygen. Oxygen is unique in that it exists in a triplet and a singlet form, and is hence ESR active. Singlet oxygen is blue and is formed in during lipid peroxidation (Kasha, 1970).

'This fact suggests that a reduced iron state, Fe(II)-PAH, trapped by oxygen with formation of an iron–oxygen intermediate, may precede the formation of the actual hydroxylating species. Enzyme-bound iron–oxygen complexes have been well documented, with cytochrome P-450 (Ullrich & Duppel, 1975; Orrenius & Ernster, 1974; White & Coon, 1980) serving as an especially pertinent example of an enzyme that catalyzes hydroxylation reactions via iron–oxygen chemistry. The fact that the prereduction step may be accomplished anaerobically with dithionite provides an approach to investigate oxygen binding to Fe(II)-PAH and subsequent intermediates for the hydroxylation reaction.' ―Wallick​

I think this article makes clear that any heme enzyme (i.e. P450s) can potentially be catalyzed by electrons, and thus are very likely redox active. I think this can occur based on the large area or the porphyrin ring, able to spread a delocalized electron across it's entire conjugated superstructure—an electron eventually collected by Fe³⁺, forming Fe²⁺, with subsequent O₂ adsorption and further catalytic activity.

Michael Kasha. "Chemiluminescence arising from simultaneous transitions in pairs of singlet oxygen molecules." Journal of the American Chemical Society (1970)​

There is a russian (translated) book that might interest you a lot, entitled: Sulfhydryl and disulfide groups of proteins - Yu. Torchinskii (ESPN 978-1-4757-0129-6)
It's a great book.

 

[haidut]

If this were true, that would make redox balance a very important control mechanism in the cell

So far I have seen nothing to refute the VERY strong evidence that ANY cancer cells are rather easy to get rid of by simply lowering the GSH/GSSG ratio inside them (and systemically) beyond a certain critical point. GSH is their main protection mechanism against both apoptosis and T-cells. The GSH/GSSG ratio depends on a number of factors but can be lowered by raising the NAD/NADH ratio, eating more sucrose, taking aspirin, quinones, etc.
"Diabetes" II seems to be the same way - disappears the moment the NAD/NADH ratio goes above a specific value (usually 500-700 in the studies I have seen).
There are quite a few older studies on PubMed from before 1950s that talk about the NAD/NADH ratio as the primary controller of differentiation. I wonder how many other "chronic diseases" are just momentary signs of excessive reductive stress, which can be reversed quite rapidly with the right tools...

 

[Amazoniac]

Alberto was aware of the balance:
A Cancer Therapy By Max Gerson - Selected Parts

 

[Travis]

So far I have seen nothing to refute the VERY strong evidence that ANY cancer cells are rather easy to get rid of by simply lowering the GSH/GSSG ratio inside them (and systemically) beyond a certain critical point. GSH is their main protection mechanism against both apoptosis and T-cells. The GSH/GSSG ratio depends on a number of factors but can be lowered by raising the NAD/NADH ratio, eating more sucrose, taking aspirin, quinones, etc.
Do you know of any enzyme/reaction in the organism that is not dependent on NAD (NADH) and/or ATP as cofactors?

Well there's enzymes which use NAD(P)(H) as cofactor, enzymes which glutathione as cofactor, and redox sensitive transcription factors in the nucleus (p53) with disulfide bridges, but I didn't think that cyclooxygenase was redox‐active in the way a person could gather from that Ray Peat quote above—a passage which might seem to imply that aromatase and cyclooxygenase cycled between thiol and disulfide form. I think it's easy to imagine an enzyme in which a disulfide bridge could be created from two thiols in close proximity, blocking the catalytic site and preventing activity.

This 25 page article on the topic mentions aromatase and cyclooxygenase not once, though it does mention dozens of others:

Ziegler. "Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation." Annual review of biochemistry (1985)​

And there are the redox‐active heme prosthetic groups as well, as shown by Wallick above.

So I got to thinking that perhaps Ray had meant that these enzymes were translated with disulfide bridges, like many are, and transported from the Golgi complex to the cytosol where they are permanently reduced to their active thiol form. I think it's easy to imaging a protein 'springing open' as internal dithiol ligatures are broken. Here is a quote from:

Braakman, Ineke. "Manipulating disulfide bond formation and protein folding in the endoplasmic reticulum." The EMBO Journal (1992)​

'Most secretory proteins and membrane glycoproteins contain disulfide bonds. These cross-links, which can form within or between polypeptides, are often crucial for the function and stability of the folded proteins as well as for their maturation and intracellular transport. The disulfides are generated through oxidation in the endoplasmic reticulum (ER), which is the compartment where most folding and oligomeric assembly events take place. The ER lumen is unique among folding compartments in the eukaryotic cell because it provides a sufficiently oxidizing environment for disulfide formation as well as an enzyme, protein disulfide isomerase, to promote the formation of disulfide bonds (see Freedman, 1989). Since the ER is not the terminal compartment for most of the proteins targeted to it, a quality control system is present that limits exit from the ER to the Golgi complex to those proteins that are fully folded and oligomerized (Hurtley and Helenius, 1989). From the Golgi complex they are transported to various destinations inside and outside the cell. Misfolded, unassembled and incompletely oligomerized proteins are generally retained in the ER and eventually degraded. For some multidomain proteins like IgG (Bergman and Kuehl, 1979), serum albumin (Peters and Davidson, 1982) and influenza hemagglutinin (HAO) (Braakman et al., 1991) it has been shown that folding and disulfide bond formation begin on the nascent chain. The co-translational folding of a typical multidomain glycopolypeptide thus proceeds vectorially from the N-terminus towards the C-terminus. When synthesis is completed, many of the disulfide bonds are already in place. Folding and disulfide bond formation continue post-translationally, resulting (usually within a few minutes) in a folded protein with a completely oxidized lumenal domain. Disulfide pairing during the folding process is, at least in part, catalyzed by protein disulfide isomerase (Bulleid and Freedman, 1988; Freedman, 1989).' ―Braakman
​

Perhaps Ray Peat had simply meant the disulfide reduction upon protein maturation—an initial even which can happen only once in most proteins. I have seen no indication that the thiol groups of aromatase play any significant catalytic role.

 

[Travis]

'The active thyroid hormone, T₃, is destroyed locally by a specific deiodinase, prostaglandins are produced by cyclooxygenase, estrogen by aromatase, and nitric oxide by its synthase. These enzymes are activated by chemical reduction of their disulfide groups, converting them to thiols, and can be inhibited by appropriate oxidants. In a healthy organism, those oxidants are available.' ―Ray Peat​

This quote below might seem to indicate the opposite of the one above: that the disulfide bonds of cyclooxygenase are necessary for full activity:

'A C69S mutation in PGHS-1, which disrupts one of the EGF disulfide bonds, lacks activity; thus an intact EGF domain is essential for folding (WL Smith, unpublished data).' ―Smith​

A ⁶⁹cysteine to ⁶⁹serine mutation makes cyclooxygenase less active, not more active as the Peat quote could imply.

Smith, William L. "Cyclooxygenases: structural, cellular, and molecular biology." Annual review of biochemistry (2000)​

 

[Wagner83]

Why don't you discuss those things with Ray too? It would be interesting (for those who can follow it) to see the back and forth between the two of you. He may be happy to have someone email him something different than the latest fart streak after indulging in burritos.

 

[Amazoniac]

A question for those that have a cotton factory in your belly buttons:

Spoiler: Does selenomethionine feed bad bacteria just as easily as methionine?

Advances in Microbial Ecology (vol. 6) - K. C. Marshall

@Travis

 

[Travis]

A question for those that have a cotton factory in your belly buttons:

Spoiler: Does selenomethionine feed bad bacteria just as easily as methionine?

Advances in Microbial Ecology (vol. 6) - K. C. Marshall
View attachment 8196

@Travis

Ahh! So the right intestinal bacteria could form polyamines and then donate them to the human intestine in a relay fashion!

Interesting, but I think extracellular polyamines are less dangerous than intracellular methionine because they are destroyed by monoamine oxidase and polyamine oxidase. I am pretty sure that there are studies showing selenomethione inhibiting polyamine synthesis in the human cell:

Redman, Claire. "Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells." Carcinogenesis (1997)​

Ah, here we go. Any doubts instilled by your comment will evaporate after viewing this table:

We have massive—massive!—reductions in the concentrations of polyamines spermidine and spermine (putrescine is just a diamine), two molecule types shown to increase dNA synthesis through inducing a left‐handed helix; these molecules take it halfway towards complete unfurlment.* The housekeeping genes cannot replicate quickly without spermine and proliferation is always inhibited by their absence (I have seen no exception to this). Spermidine is less effective at catalyzing dNA replication than spermine, and putrescine is ineffective—a paper tiger, dangerous only to the degree that it can later be polymerized to spermidine/spermine.

* Is that really a word? ​

 

[Syncopated]

I had a typo in the above comment.

It should have read : OPT (ortho-phospho-tyrosine as a metastatic cancer marker.

Eggs are no longer a concern for polyunsaturates. Separate out the yolks and blend the raw egg whites with orange juice, delicious.

The best way to separate out the yolks is using the egg shells, altering between cracked halves until the egg white is fully gone. Then place the shell and yolk back into the carton.