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Palytoxin expertise needed!


mario.jean.24

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Hello there! 

I recently did a presentation in my university about Palytoxin.

Someone asked a very good question that I didn't know the answer to and have been unable to find.

So I'm hoping someone out there knows the answer.

 

Palytoxin is such a large molecule, so how does it cross different barriers in the body? For example breathing and crossing the skin layer? If its molecules are so big shouldn't it not affect us? 

 

Let me know if you might know the answer!

 

Mario

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Hello there! 

I recently did a presentation in my university about Palytoxin.

Someone asked a very good question that I didn't know the answer to and have been unable to find.

So I'm hoping someone out there knows the answer.

 

Palytoxin is such a large molecule, so how does it cross different barriers in the body? For example breathing and crossing the skin layer? If its molecules are so big shouldn't it not affect us? 

 

Let me know if you might know the answer!

 

Mario

Good question, Mario. You probably need the expert opinion of a toxicologist on this one. The people here that have been affected by it have often suffered after inhalation exposure. That may provide some insight.

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Ha. You can search anything on the net these days:

 

http://en.wikipedia.org/wiki/Palytoxin

 

The toxicity of palytoxin is due to its binding to Na+,K+-ATPase (sodium pump), where it interacts with the natural binding site of ouabain with very high affinity. Na+,K+-ATPase is a transmembranal protein, which is found on the surface of every vertebrate cell. Also, the sodium pump is necessary for viability of all cells, and this explains the fact that palytoxin affects all cells.[17] Palytoxin is the first toxic compound found to cause formation of a channel. Through this channel, which it forms within the sodium pump, monovalent positive ions such as sodium and potassium can diffuse freely thereby destroying the ion gradient of the cell.[18][19] Once palytoxin is bound to the pump, it flips constantly between open and normal conformations. The open conformation is more likely (>90% probability). If palytoxin disscociates, the pump will return to closed conformation.[20] In open conformation, millions of ions diffuse through the pump per second, whereas only about one hundred ions are transported through a normal functioning transporter.[20]

Because the mechanism of action of palytoxin was so unlike any other, it was initially not widely accepted. This was primarily because it was not expected that a pump which provides active transport, could become an ion channel by binding of a compound such as palytoxin.[17] Therefore, there were some alternative hypotheses, which were reviewed by Frelin and van Renterghem in 1995.[21] The breakthrough research which is seen as proof for the sodium pump mechanism was performed in yeast cells. These cells do not have the sodium pump, and hence palytoxin does not affect them. But once they were given the DNA to encode for complete sheep Na+,K+-ATPase, they were killed by palytoxin.[22]

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From the same Wikipedia article, "Another person was exposed to palytoxin via inhalation[34] when he tried to kill a Palythoa in his aquarium with boiling water."

 

Steve, you're famous (infamous?) yet again. (Not 100% accurate as written, but we know it's you that they're talking about.)

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Palytoxin is such a large molecule, so how does it cross different barriers in the body? For example breathing and crossing the skin layer? If its molecules are so big shouldn't it not affect us? 

 

And the flip side of this is that if it were not effective toxin in the broadest sense, it probably wouldn't be part of their defensive mechanism. In any case, it appears that a reasonable offering is provided in the Wikipedia article that I linked to above.

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From a toxicology point of view, the size of the molecule almost never matters. Take the protein ricin for example. That molecule is more than 10X larger than palytoxin and it can kill you by inhalation. 

 

By definition, a toxin is able to bypass one or more of our defensive strategies and barriers by absorption. When these molecules are able to bypass our defenses, the effects are usually devastating. 

 

How humans are exposed to a toxin is of top concern to a toxicologist since different barriers are more susceptible to others,

 

For example, Palytoxin is not very potent when exposed to uninjured skin because it doesn't readily pass through the skin. However, if there is even a small scratch on the skin, then all bets are off. And if you inject yourself with it or breath it in, then good night.

Edited by jaddc
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I thought they said "wait, what?" and asked him to tell them about palytoxin.

 

Alan wins the prize.  They had no idea what made my lungs collapse.  They just kept jacking me full of steroids and put me on a respirator.  All the while the doctor was on the internet looking up this crazy palytoxin stuff.  The worst part was when she gave me the steroid and said "I hope this stuff works".

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... "I hope this stuff works".

Remind me to put this on my "words I don't want to hear coming from my doctor" list.

 

And thanks, Jeff, for weighing in.

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Alan wins the prize.  They had no idea what made my lungs collapse.  They just kept jacking me full of steroids and put me on a respirator.  All the while the doctor was on the internet looking up this crazy palytoxin stuff.  The worst part was when she gave me the steroid and said "I hope this stuff works".

Steroids seem to be their first line of defense... :)

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I'm a PhD toxicologist myself and wrote about some of the toxins in our hobby ages ago.. wow 2002 and 2003 (I put the links below).  People have already hit on it here (yay for wikipedia), but the route of exposure matters.  You are correct in that it is a fairly large molecule, but it has specific receptors (which all toxicants do) that it will bind extracellularly.  It doesn't penetrate the cells (from what I recall), but it is effective without needing to doing so.  Breaking a barrier (skin or other membrane) will certainly cause it to be effective.

 

 

 

http://www.advancedaquarist.com/2002/6/aafeature

 

http://www.advancedaquarist.com/2003/4/aafeature

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