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cycling between states and the electron transport chain

methylene blue

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#1 ClarkSims

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Posted 26 January 2013 - 05:38 PM


I was reading this paper by Gonzalez and Lima about Methylene Blue's role in the electron transport chain.
http://www.dose-resp...nzalez Lima.pdf

They have some nice charts about how it cycles between oxydized and reduced states, and participates in the electron chain


http://acumensoftwar...om/mb_cycle.png


http://acumensoftwar...donor_chain.png

They then note, that the cycle breaks down, if there is too much MB, because it no longer cycles between states, but instead just takes electrons away from the chain:


At low doses, there is MB‐MBH2 equilibrium (electron
cycling) and MBH2 can donate electrons to ETC
complexes and oxygen, leading to enhanced energy
metabolism and decreased superoxide formation
• At high doses, equilibrium is impaired and MB can take
electrons away from ETC complexes, leading to
decreased activity of these complexes and more
oxidative stress

The chemistry for C60 would work the same with the difference that if C60 acquired too many electrons, it would cause an electrical charge on the mitochondria. The electrical charge would eventually prevent it from acquiring more electrons, thus limiting the amount it could acquire.

Put another way, the C60 adducts in the membrane of the mitochondria should never accept so many electrons that they hinder the electron chain, because they are limited to the surface of the mitochondria, and the electrical charge prevents them from accepting too many electrons. In contract MB, is distributed all over the cell, and the oxidized (charged) form, is hydrophilic, and will be surrounded by H2O which has a large dialectric constant.

Any thoughts?

#2 AdamI

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Posted 26 January 2013 - 05:43 PM

I got 2.
How much time would it take for C60 to reach this degree. Since a cell eventualy dies and renews itself, the c60 would then vanish with the dead cell.
Soo does C60 reach this state very fast or over a such along period that it is rather pointless being afraid of that state since it never happens, the cell renews itself before perhaps?

The second one abour MB, what dose do they recommend is a good one and how much is to much:)?

Click HERE to rent this advertising spot for C60 HEALTH to support Longecity (this will replace the google ad above).

#3 ClarkSims

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Posted 26 January 2013 - 05:54 PM

The C60 adduct can accept an electron very quickly, almost instantly. The charge buildup on the surface of the mitochondria would be a function of how many O2- or other ROS species were dumping electrons. The charge buildup should be self limiting because of the energy required to put a charge on a small object. The charge dissipation would be function of how quickly the C60 adduct, could give electrons to H+ ions, and other compounds willing to receive a H atom.

There were talking about 1 mg / Kg / day of tissue as the optimal dose for a rat. Presumably that would be less for humans, because we have s slower metabolism. For a 70 Kg human, that works to be 70 mg / day. The optimal dose in the Rember trials was 50 mg per day. I am taking about 30 mg / day.

#4 niner

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Posted 26 January 2013 - 07:23 PM

Clark, it sounds like what you're getting at is what is known as the "reduction potential" of C60. C60 can accept up to six electrons, and each one requires a greater driving force as expressed in volts or millivolts. Fullerene reduction potentials have a strong dependence on solvent. The reduction potential will decrease in a polar, h-bonding solvent like water. Measurements have been done in a variety of solvents and in the gas phase, but I don't know what the effective values would be in the mitochondrial membrane. Across a variety of solvents, an increase of about 400-500 mV for each added electron is typical. I don't think that c60 will hold a negative charge for a long time; donating that electron to something that could electrically neutralize it should be energetically favored. Also, if the c60 was negatively charged, it would be a lot less good of a superoxide dismutase mimetic, since the negative charge would repel the superoxide anion. I don't know if c60 is contributing electrons to the ECT like MB does, or not. The reduction potential of MB is near zero, while I doubt that the first one for c60 is less than 100 mV. C60 certainly acts like it is dramatically improving the efficiency of mitochondria in some disease states, but I don't know what the mechanism for that is.

#5 niner

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Posted 26 January 2013 - 07:29 PM

Since a cell eventualy dies and renews itself, the c60 would then vanish with the dead cell.


When a cell dies, the components are hydrolyzed into basic building blocks like amino acids, fatty acids, nucleotides, etc and re-used. Thus I don't think the c60 will vanish. A lot of it should end up getting incorporated into other cells, including new ones. It must gradually be lost over time, although I don't think anyone has a firm handle on the half life. All I can say is it's pretty long.

#6 AdamI

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Posted 26 January 2013 - 07:46 PM

I see, thought that white blood celled consumed it and then is rejected from the body... although just something I thought it did. Soo the body is recycling, didn't really know that:)

#7 ClarkSims

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Posted 26 January 2013 - 08:06 PM

Clark, it sounds like what you're getting at is what is known as the "reduction potential" of C60. C60 can accept up to six electrons, and each one requires a greater driving force as expressed in volts or millivolts. Fullerene reduction potentials have a strong dependence on solvent. The reduction potential will decrease in a polar, h-bonding solvent like water. Measurements have been done in a variety of solvents and in the gas phase, but I don't know what the effective values would be in the mitochondrial membrane. Across a variety of solvents, an increase of about 400-500 mV for each added electron is typical. I don't think that c60 will hold a negative charge for a long time; donating that electron to something that could electrically neutralize it should be energetically favored.


When it donates that electron, it is acting like MB when it donates the electron. The MB cycles between charges of 0 and +1. C60-adduct, cycles between -1 and 0.


Also, if the c60 was negatively charged, it would be a lot less good of a superoxide dismutase mimetic, since the negative charge would repel the superoxide anion. I don't know if c60 is contributing electrons to the ECT like MB does, or not. The reduction potential of MB is near zero, while I doubt that the first one for c60 is less than 100 mV. C60 certainly acts like it is dramatically improving the efficiency of mitochondria in some disease states, but I don't know what the mechanism for that is.


We are getting at the same thing here. There should never be an imbalance in the states of C60, where it absorbs so many electrons, that it lowers the efficiency of the electron transport chain.

I am also getting at the C60 is confined to the membrane of the mitochondria, so it can't go to another part of the cell while carrying a charge, like MB can.

#8 niner

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Posted 27 January 2013 - 01:12 AM

I am also getting at the C60 is confined to the membrane of the mitochondria, so it can't go to another part of the cell while carrying a charge, like MB can.


Yeah, this is a good point. MB is small and mobile, and is sufficiently hydrophilic to live in water, although it has enough hydrophobic surface to deal with lipids as well. This makes it well suited to jump between complexes of the ETC. C60, on the other hand, is almost certainly membrane bound. I don't know enough about the architecture of the ETC to say if it could shuttle an electron between complexes without leaving the membrane. Maybe it doesn't have to go from protein to protein, but interacts with a smaller molecule that in turn interacts with a complex? I dunno. I can say that a number of people using c60 have seen what looks very much like enhanced mitochondrial efficiency in hypoxic situations. Could it be something like the electrons that leak out in the form of superoxide anion being usefully recycled into the ETC? Superoxide is very mobile, so it could easily find a membrane-bound c60. Whatever happens next is the question mark.

#9 rashlan

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Posted 27 January 2013 - 04:32 AM

The C60 adduct can accept an electron very quickly, almost instantly. The charge buildup on the surface of the mitochondria would be a function of how many O2- or other ROS species were dumping electrons. The charge buildup should be self limiting because of the energy required to put a charge on a small object. The charge dissipation would be function of how quickly the C60 adduct, could give electrons to H+ ions, and other compounds willing to receive a H atom.

There were talking about 1 mg / Kg / day of tissue as the optimal dose for a rat. Presumably that would be less for humans, because we have s slower metabolism. For a 70 Kg human, that works to be 70 mg / day. The optimal dose in the Rember trials was 50 mg per day. I am taking about 30 mg / day.


Can somebody settle this for me, I thought that the rember optimal dose was 180 mg split in three doses so 60 mg per dose.

#10 ClarkSims

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Posted 27 January 2013 - 03:10 PM

Can somebody settle this for me, I thought that the rember optimal dose was 180 mg split in three doses so 60 mg per dose.


The only detailed description of the rember trials that I can find is here:
http://www.alzforum....ail.asp?id=1892
Does anyone know, if SigmaTau ever published something?

I misquoted the study. Thank you for pointing out the error. The description says:
"The company conducted a Phase 2 study randomizing 321 people with mild or moderate AD to treatment with either placebo or one of three oral doses of MTC: 30 mg, 60 mg, or 100 mg three times a day. People taking AD drugs, i.e., acetylcholinesterase inhibitors or memantine, were excluded. "

So you are correct as best as I can tell, and it was 60 mg , 3 times per day.





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