Just Started Methylene Blue

[Travis]

Hey buddy, I found this video from the ufc. It looks as though a heavyweight Francis Ngannou has the hardest punching power ever recorded. The guy in the video seems to describe how they measure the power.
starts @ 6:48


I think it would be interesting if they tested all fighters punching/kicking power, and had the stats available for people who bet on sports

I was also searching for other sports records like hockey/baseball/running/golf etc and found that most of the body types are around 6'3" to close to 6'8" tall and similar weight profiles depending on event.
(approx height/weight)
Usain Bolt(running speed) 207lbs/6'4"
Aroldis Chapman(fastest pitch) 211lbs/6'3"
Zdeno Chara(hockey shot) 255lb/6'8"
Joe Miller(golf distance) 265lbs/6'4"
Sam Groth(tennis speed) 220lbs/6'4"
Francis Ngannou (punch power) 262lbs/6'5"

I bet it's piezoelectric. The compression of quartz, and a few other crystals, actaully slightly deforms it. This leads to electrons being forced out of the crystal as they repel each other—being of opposite charge and forced to occupy a closer arrangement. These displaced electrons can be made to flow down a wire, as can be demonstrated by the illumination of a light bulb with a quartz crystal, hammer, and copper wire. Many modern scales are, in fact, piezolectric.

The coolest thing about piezoelectricity is that the converse holds: Forcing electrons into a quartz lattice will cause it to deform slightly. This has applications in actuators, as those found in microscopes which are made to precisely adjust slides at high magnification.

Quartz has largely replaced the spring, and for good reason.

That boxer looks brutal, and I'm nearly certain that he could take on two grizzly bears at once. Humans who actually move around all day and eat properly can be pretty formidable creatures.

 

[Regina]

I bet it's piezoelectric. The compression of quartz, and a few other crystals, actaully slightly deforms it. This leads to electrons being forced out of the crystal as they repel each other—being of opposite charge and forced to occupy a closer arrangement. These displaced electrons can be made to flow down a wire, as can be demonstrated by the illumination of a light bulb with a quartz crystal, hammer, and copper wire. Many modern scales are, in fact, piezolectric.

The coolest thing about piezoelectricity is that the converse holds: Forcing electrons into a quartz lattice will cause it to deform slightly. This has applications in actuators, as those found in microscopes which are made to precisely adjust slides at high magnification.

Quartz has largely replaced the spring, and for good reason.

That boxer looks brutal, and I'm nearly certain that he could take on two grizzly bears at once. Humans who actually move around all day and eat properly can be pretty formidable creatures.

There is also the willingness of the fighter to connect his powerful fist to someone's face. What is that?
The times that I have grazed someone (in aikido) who didn't move left me unable to train for a while.

 

[Travis]

There is also the willingness of the fighter to connect his powerful fist to someone's face. What is that?
The times that I have grazed someone (in aikido) who didn't move left me unable to train for a while.

I think it's the serotonin and/or histamine.

When I was eating primarily raw goat cheese, raw kale/lettuce, and fruit, I think I was at my most nice (think about Swedish people). But eating to many eggs or grains makes be a bit too crazy, perhaps by affecting serotonin and/or histamine.

I wouldn't want to hit a stranger like that, but I know of some people.. . .

 

[ilikecats]

@haidut definitely has a point. A lot of the biggest punchers in the history of boxing were very lanky with little to moderate muscle mass. Check out bob foster, Tommy hearns (6 foot 1 fought at 147), Alexis Arguello, Sugar Ray Robinson, Joe Louis, Gerald McLellan, and Julian Jackson. Most of those guys were harder (or equal) pound for pound punchers than mike tyson in my opinion. One of my favorite boxers of all time was Ricardo "el finito" Lopez who was 5 foot 5 and fought at 105 pounds. He looks completely anorexic and IMO he's one of the hardest punching boxers of all time. Retired 51-0-1. Ricardo Lopez:
just listen to the punch at 0:46 in the Ricardo Lopez video, you can hear it land throughout the stadium!
Bob Foster:

 

[ilikecats]

.

 

[Regina]

I think it's the serotonin and/or histamine.

When I was eating primarily raw goat cheese, raw kale/lettuce, and fruit, I think I was at my most nice (think about Swedish people). But eating to many eggs or grains makes be a bit too crazy, perhaps by affecting serotonin and/or histamine.

I wouldn't want to hit a stranger like that, but I know of some people.. . .

So, I guess serotonin is a necessary job hazard for these fighters.

It's probably not possible to have a high-level aikido dojo focused on 'stress without distress'. No one would want it.

 

[Travis]

So, I guess serotonin is a necessary job hazard for these fighters.

It's probably not possible to have a high-level aikido dojo focused on 'stress without distress'. No one would want it.

It is possible to compete safely, but our most popular sports are violent. Football, boxing, and hockey are pretty rough; baseball, soccer, and tennis are rather nonviolent (though there has been exceptions). Basketball used to safe, but it can get rough with bigger people with massive egos fueled by equally massive paychecks. The only thing I can bring myself to watch is tennis, although NCAA basketball can be exciting.

The only game I play is chess. The cool thing about it, like reading, is that it provides a gauge for the brain state. My rating fluctuates from ~1500–1800, seemingly depending mostly on serotonin and histamine—and β-casomorphin if I eat cheese. Caffeine and nicotine levels do play a role, but I can't think of too many other factors.

I just went shopping and I have coconuts, kale, pineapples, orange, dates, and coffee. This represents high vitamin C, folate, caffeine, and microgram-levels of linoleic acid. No immunogenic proteins to speak of and no opiates. Although my chess rating is at a pathetic ~1550 right now, I do expect to get back over 1700 within a week or two.

 

[haidut]

@haidut definitely has a point. A lot of the biggest punchers in the history of boxing were very lanky with little to moderate muscle mass. Check out bob foster, Tommy hearns (6 foot 1 fought at 147), Alexis Arguello, Sugar Ray Robinson, Joe Louis, Gerald McLellan, and Julian Jackson. Most of those guys were harder (or equal) pound for pound punchers than mike tyson in my opinion. One of my favorite boxers of all time was Ricardo "el finito" Lopez who was 5 foot 5 and fought at 105 pounds. He looks completely anorexic and IMO he's one of the hardest punching boxers of all time. Retired 51-0-1. Ricardo Lopez:
just listen to the punch at 0:46 in the Ricardo Lopez video, you can hear it land throughout the stadium!
Bob Foster:

Wow, thanks for those videos!
The Ricardo video has another loud punch, around 1:01 mark. You can tell he punches VERY hard as his opponents simply drop on the ground like flies. No wobbling, no holding of the ropes. Just pass out.
I also bet those hard punchers maintain vitality pretty much their whole life. Punch strength, like grip strength, is a very good predictor of male health. Muscle mass, not so much.

 

[Kyle M]

Methylene blue is an oxidant not a methyl donor. B vitamins are methyl donors, is that supposed to be a bad thing? I don't understand the alkylating agent/methyl donor problem as stated from that "zapper" woman.

The reason why a lot of bulky, bodybuilder-type guys have weak punching power in ratio to their size is the loss of kinetic transference. The "kinetic chain" of striking, as well as why some people can take a hard blow without being knocked out, are two very interesting questions. There is clearly a difference between someone with big muscles who naturally has a big frame and trains their body with punching, and someone who builds huge muscles from a smaller starting frame through heavy barbell lifts. The ability of the muscle and bone groups to transfer their kinetic energy from one to the other is reduced in the latter. I imagine in my head energy dissipating into the tissues from movement to movement.

A punch starts in the feet, the force comes from being rooted to the ground in your feet. Pushing against the ground, the legs force the hips to rotate. This energy follows up to the shoulder and, one hopes, out through the punching arm. To get an idea of what maximum transference feels like, try pushing against a wall with your dominant hand, turned and bent as far as you need to in order to push as hard as you can. This is where your punch should land, and the force of your push is coming from your feet pushing off of the ground and that force traveling through hips and up through shoulder.

 

[Travis]

But mono‐ and di‐demethylated metabolites of methylene blue—azure B and azure A, respectively—have routinely been detected in the tissue and urine of humans.

'Examination of autopsied peripheral organs of a patient receiving intravenous MB have showed that the concentrations of MB in these tissues were 74–208 ng/g while the concentrations of azure B (475–2943 ng/g) were significantly higher.' ―Petzer
​

Thus, methylene blue is either (1) A 'methyl donor,' or (2) Methyl groups can vanish, violating established Conservation of Mass Laws.

I think it would be easier for most people to accept choice #1.

Petzer, Anél. "Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase." Toxicology and applied pharmacology (2012)​

 

[Kyle M]

All drugs get metabolized, being a "methyl donor" is not a monolithic label. Single carbon metabolism is a particular set of reactions having to do with cofactors, but methylated compounds can lose their methyl groups in all kinds of ways.

Now, personally, if a chemical primarily acts one way, and has a secondary affect, I would call it the former. Even if some of the methyl groups of MB end up getting taken off and put into single-carbon metabolism, the primary effect is still as an electron sink.

Still wondering why single-carbon metabolism is bad now.

 

[Travis]

Now, personally, if a chemical primarily acts one way, and has a secondary affect, I would call it the former.

Who wouldn't? But of course doing so doesn't negate the secondary label.

So it can accept one electron, similar to flavin, as it cycles from methylene blue to its leuko form. However! it still loses methyl groups. And to what? I don't know, but they certainly are donated to something. Molecules like betaine are thought to contribute to the conceptual 'methyl pool,' but I don't think it's ever been conclusively shown exactly how.. . .

Has methane been determined in the blood? . . . [searching] . . . It has, and it can be detected in expired breath in low part per million concentrations. So perhaps there's still a way for you to weasel out of this one Kyle?

'Methylene blue does not 'donate methyl groups,' but simply releases methane which is then expired.' ―What a person could say.. . .​

Karlin, David A. "Breath Methane Excretion in Patients With Unresected Colorectal Cancer 2." Journal of the National Cancer Institute (1982)

 

[Regina]

Methylene blue is an oxidant not a methyl donor. B vitamins are methyl donors, is that supposed to be a bad thing? I don't understand the alkylating agent/methyl donor problem as stated from that "zapper" woman.

The reason why a lot of bulky, bodybuilder-type guys have weak punching power in ratio to their size is the loss of kinetic transference. The "kinetic chain" of striking, as well as why some people can take a hard blow without being knocked out, are two very interesting questions. There is clearly a difference between someone with big muscles who naturally has a big frame and trains their body with punching, and someone who builds huge muscles from a smaller starting frame through heavy barbell lifts. The ability of the muscle and bone groups to transfer their kinetic energy from one to the other is reduced in the latter. I imagine in my head energy dissipating into the tissues from movement to movement.

A punch starts in the feet, the force comes from being rooted to the ground in your feet. Pushing against the ground, the legs force the hips to rotate. This energy follows up to the shoulder and, one hopes, out through the punching arm. To get an idea of what maximum transference feels like, try pushing against a wall with your dominant hand, turned and bent as far as you need to in order to push as hard as you can. This is where your punch should land, and the force of your push is coming from your feet pushing off of the ground and that force traveling through hips and up through shoulder.

Kuroda Sensei says one of the most important "secrets" of martial arts is to NOT push the ground/floor. He has phenomenal speed and kime.

 

[Kyle M]

Kuroda Sensei says one of the most important "secrets" of martial arts is to NOT push the ground/floor. He has phenomenal speed and kime.

I don't know who that is, but I've spent enough time with real boxers and boxing trainers to feel confident in my technique. If Kuroda Sensei or someone ascribing to his ideas wants to show me in sparring how that works, I'd be glad to guinea pig.

 

[Kyle M]

Has methane been determined in the blood? . . . [searching] . . . It has, and it can be detected in expired breath in low part per million concentrations. So perhaps there's still a way for you to weasel out of this one Kyle?

What I mean to say is that the "methyl pool" is not a real thing, everything is partitioned. Just as you cannot simply ingest an enzyme if you have a deficiency of it in one of your tissues (problems of delivery) a molecule losing methyl groups somewhere on its journey being metabolized in your body isn't necessarily involved in the same reactions as a dedicated single-carbon metabolism agent, like SAM. It may be, and it may not be.

Still though, can someone (Travis I guess) explain to me what is bad about single-carbon metabolism? And by bad I mean pathological.

 

[Regina]

I don't know who that is, but I've spent enough time with real boxers and boxing trainers to feel confident in my technique. If Kuroda Sensei or someone ascribing to his ideas wants to show me in sparring how that works, I'd be glad to guinea pig.

 

[Travis]

What I mean to say is that the "methyl pool" is not a real thing, everything is partitioned. Just as you cannot simply ingest an enzyme if you have a deficiency of it in one of your tissues (problems of delivery) a molecule losing methyl groups somewhere on its journey being metabolized in your body isn't necessarily involved in the same reactions as a dedicated single-carbon metabolism agent, like SAM. It may be, and it may not be.

Still though, can someone (Travis I guess) explain to me what is bad about single-carbon metabolism? And by bad I mean pathological.

I think you're right. I don't see any reason to assume these methyl groups would necessarily end up on SAM, homocysteine, or cobalamin's central cobalt atom—especially considering the fact that methane is expired. For all I know, the term 'methyl donor' really could be a misnomer.

I think the most pathological thing having to do with methyl groups is of course the lack of them, in the case of hyperhomocysteinemia and Down's syndrome. Homocysteine seems to have a peculiar ability to form a free radical as the terminal thiol (sans hydrogen) bends around and plucks a hydrogen off the α-carbon—forming a stable tertiary free radical on the α-carbon. Cysteine apparently cannot do this because its 'γ-tail' is not long enough. The longer tail of homocysteine would also make it more lipophilic, increasing the partition constant towards the lipid membrane. The homocysteine radical has been very strongly associated with lipid peroxidation, with Pearson coefficients between cerebospinal fluid homocysteine and hydroxynonenal approaching unity:

'There were significant positive correlations between the CSF concentrations of homocysteine and HNE (r 0.924, P 0.001). There was also a significant positive correlation between the plasma concentration of homocysteine and the CSF concentrations of homocysteine (r 0.850, P 0.007)...' —Selley​

Thus, the massive IQ deficits seen in Down's syndrome and hyperhomocysteinemia could fundamentally be a result of lipid peroxidation and the subsequent Shiff‐lysine crosslinks you'd expect to result.

'Down’s syndrome (DS), or trisomy 21, is the most frequent genetic cause of mental retardation. It results from the gene expression of an extra chromosome 21[...] The MTHFR 677 C➝T and MTRR 66 A➝G polymorphisms are associated with a greater risk for mothers to have a child with DS. [...] In addition, IQ was associated with t-Hcys independently of age in the multiple regression analysis.' —Gueant​

Dementia is associated with high levels, greatly increasing around the 15·μmol/L range. People with hyperhomocysteinemia and Down's can have levels upwards of 40·μmol/L—and with an IQ to match.

Besides homocysteine, the effects 3‐methoxytyramine have also been well studied. This is O‐methylated dopamine, yet only seems to be a factor in those taking L‐Dopa (i.e. Parkinson's). There is even reason to believe the characteristic dyskinesia seen in Parkinson's simply a result of this one metabolite. There are a two polymorphisms of COMT, and there's been many studies on this enzyme's activity and intelligence (with results going both ways, but tending towards increased intelligence with lower catechol methylation.)

And methane is a general anesthetic. While Linus Pauling's theory is interesting, I think it is incorrect. After the Pauling article, it had been shown that anesthetic potency correlated very strongly with it's partition coefficient in olive oil. Later, it had been shown to have a slightly greater partition coefficient in phosphitidylcholine—the main constituent of myelin behind progesterone and pregnenolone. This leaves me to assume that general anesthetics don't work by forming a clathrate cage in the aqueous phase (Pauling, 1964), but instead intercolate inside of microtubules where they quench fluorescence—another well‐known property of anesthetics. (Microtubules are always found in the centre of nerves surrounded by myelin.)

Pauling, Linus. "The Hydrate Microcrystal Theory if General Anesthesia." Anesthesia & Analgesia (1964)
Gueant, J. L. "Homocysteine and related genetic polymorphisms in Down’s syndrome IQ." Journal of Neurology, Neurosurgery & Psychiatry (2005)
Schumacher, Michael. "Progesterone synthesis in the nervous system: implications for myelination and myelin repair." Frontiers in neuroscience (2012).
Janoff, Andrew S. "Correlation of general anesthetic potency with solubility in membranes." Biochimica et Biophysica Acta (BBA)-Biomembranes (1981)
Koblin, Donald D. "The penetration of local anesthetics into the red blood cell membrane as studied by fluorescence quenching." Archives of biochemistry and biophysics (1975)
Selley, M. L. "The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer’s disease." Neurobiology of aging (2002)​

 

[Kyle M]

I think you're right. I don't see any reason to assume these methyl groups would necessarily end up on SAM, homocysteine, or cobalamin's central cobalt atom—especially considering the fact that methane is expired. For all I know, the term 'methyl donor' really could be a misnomer.

I think the most pathological thing having to do with methyl groups is of course the lack of them, in the case of hyperhomocysteinemia and Down's syndrome.

In other words, thinking MB is "bad" because of its potential as a donor of a methyl group doesn't make sense?

Hey since you have all of these numbers lying around, I have a question I have gone to great pains to answer but have failed so far. I'm looking for the energy needed to oxidize acyl chains. Specifically, as PUFA are said to be oxidizable at body temperature while saturated and monosaturated fats are not, I want to find the activation energy for a radical to attack the carbon between two conjugated double bonds. That's the one susceptible to hydrophilic attack and oxidation. Do you have a book with those kinds of basic organic chemistry numbers?

 

[Travis]

In other words, thinking MB is "bad" because of its potential as a donor of a methyl group doesn't make sense?

Hey since you have all of these numbers lying around, I have a question I have gone to great pains to answer but have failed so far. I'm looking for the energy needed to oxidize acyl chains. Specifically, as PUFA are said to be oxidizable at body temperature while saturated and monosaturated fats are not, I want to find the activation energy for a radical to attack the carbon between two conjugated double bonds. That's the one susceptible to hydrophilic attack and oxidation. Do you have a book with those kinds of basic organic chemistry numbers?

I think you could be looking for the hydrogen dissociation energy. Since that carbon in question (call it the χ‐carbon) is flanked by two double bonds, its hydrogens will be more acidic* than those of saturated carbon chains. For this carbon to accept O₂, would not it first need to lose a hydrogen? After losing this relatively acidic hydrogen, there would be a radical on the χ‐carbon which could then react with O₂. I think the pKa of the χ‐carbon would be the value to acquire.

[*] Both the hydrogens have the same acidity, initially, but only one will be removed at this pKa. The second hydrogen could theoretically by abstracted, but this would be at a different pKa because the loss of the initial hydrogen would increase the affinity of the second hydrogen for the carbon atom.​

And luckily, there's a simple equation relating the acid dissociation constant (Ka) with Gibbs Free Energy (ΔG). The Ka is related to the Gibbs Free Energy by this equation:

ΔG = −R·T·lnKa​

The 'p' in 'pH'—and in 'pKa'—does not signify 'potential,' as some people appear to think. The 'p' in these terms simply means the logarithm base ten. To get Ka—it appears to me—one must add a minus sign and then take the anti‐logarithm base ten (−pKa = log(Ka)). This value, or Ka, is then funneled through a natural logarithm (ln) function. The 'R' and 'T' are of course constants, so the only think left would be to find the pKa of the χ‐carbon—or the carbon in between two conjugated double bonds. .

I couldn't find the pKa, but I found this.⁽¹⁾ This chemist has the lipid just spontaneously losing a hydrogen in this mechanism (step 2 ⟶ 7)—ostensibly becoming hydronium (H₃O⁺). I see this as confirmation of the general idea that the initial hydrogen's pKa funneled through the Gibbs Free Energy equation above could be the value you are searching for.

I couldn't find the second pKa. Obviously, most first‐page results are going to be for the pKa of the carboxyl group, but I think perhaps you could find the pKa of this so‐called χ‐carbon somewhere. Perhaps a generic value would do, or a value representing the pKa between any two double bonds on a straight carbon chain. I don't really think it would take too long to find; that is, if you accept this approach.

[1] Porter, Ned A. "Unified mechanism for polyunsaturated fatty acid autoxidation. Competition of peroxy radical hydrogen atom abstraction, beta.-scission, and cyclization." Journal of the American Chemical Society (1981)​

 

[Kyle M]

I think you could be looking for the hydrogen dissociation energy. Since that carbon in question (call it the χ‐carbon) is flanked by two double bonds, its hydrogens will be more acidic* than those of saturated carbon chains. For this carbon to accept O₂, would not it first need to lose a hydrogen?

Correct, I should have said that but I meant it as all one step, where the radical absconds the hydrogen with an electron and replaces it with an O2. Thanks for the info, it is hard to find these basic measurements that should be available sometimes, isn't it?