Palytoxin...The issue has come up many-a-time

[Caesar777]

Just an interesting article I found over at WWM...

 

The Fantastic Story of the Modern Discovery of Palytoxin

 

This article was written by Professor Bob Williams of Colorado State University, for his publication: The Nerd Street Journal.

Palytoxin was discovered by Professor Paul J. Scheuer at the University of Hawaii. The story of how this toxin, and its producing organism was found is quite interesting. Prof. Scheuer has made a hobby of reading ancient Hawaiian folklore through various library collections on the islands. He came across a reference to Limu make o Hana (deadly seaweed of Hana) in his readings. This is the Hawaiian phrase for a toxic organism which Malo (Hawaiian Antiquities, 1951) described as follows: "In Muolea, in the district of Hana (Maui), grew a poisonous moss in a certain pool or pond close to the ocean. It was used to smear on the spear points to make them fatal.....The moss is said to be of a reddish color and it is still to be found. It grows nowhere else than at that one spot." According to Hawaiian legend (manuscript notes by Katherine Livermore on file at B. P. Bishop Museum, Honolulu), there lived in the Hana district a man who always seemed to be busy planting and harvesting. Whenever the people in the neighborhood went fishing, upon their return, one of the group was missing. This went on for some time without the people having any explanation about the disappearances. At last the fishermen became suspicious of the man who tended his taro patch. They grabbed him, tore off his clothes and discovered on his back the mouth of a shark. They killed and burned him and threw the ashes into the sea. At the spot where this happened, so goes the legend, the limu (moss) became toxic. The tidepool containing the poisonous limu subsequently became kapu (taboo) to the Hawaiians. They would cover the limu with stones and were very secretive about its location. They firmly believed that disaster would strike if anyone were to attempt to gather the toxic limu (later named Palythoa).

Prof. Scheuer collaborated with Professors A.H. Banner and P. Helfrich of the Hawaii Institute of Marine Biology, and through a very elaborate chain of local Hawaiian informers and several cases of beer to loosen (frightened) lips, the location of the fabled tidepool was reluctantly disclosed. The tidepool was located at the end of a lava flow at Muolea (Kanewai), south of Hana, Maui. Divers collected a small sample of the toxic limu on December 31st, 1961. During the collection, local residents reminded the collection team of the kapu and the high probability of impending misfortune. Coincidentally, that same afternoon, a fire of unknown origin destroyed the main building of the Hawaii Marine Laboratory at Coconut Island, Oahu (the Institution of Drs Banner and Helfrich). Scuba divers have subsequently combed the surrounding ocean front near the tidal pool and did not find the Palythoa growing anywhere else except in the original location pointed out by local residents. The tide pool turned out to be just six feet long, two feet wide, and 20 inches deep at low tide. The crude ethanol extracts of the Palythoa toxica proved to be so toxic that an accurate LD50 was difficult to determine. More recently, the toxicity has been determined to be 50-100ng/kg i.p. in mice. The compound is an intense vasoconstrictor; in dogs, it causes death within 5 min at .06ug/kg. By extrapolation, a toxic dose in a human (obviously not determined) would be about 4 micrograms!!!. It is the most toxic organic substance known.

Following the isolation of the crude toxin by Scheuer (reported in Science (1971) 172, p.495), it was nearly 11 years before the correct structure was unraveled. two research groups, one at the University of Hawaii (led by Prof. Richard Moore, a student of Scheuer's) and one at Nagoya University (led by Prof. Hirata) put together the correct chemical structure in late 1981. Following that, Prof. Yo######o Kishi at Harvard University decided to try the complete chemical synthesis of the Palytoxin molecule. This monumental task was completed in 1989.

The Palytoxin molecule has the longest contiguous chain of carbon atoms known to exist in a natural product(115).The molecule has the formula C129H223N3O54 and contains 64 stereogenic centers. Adding this with the double bonds that can exhibit cis/trans isomerism means that Palytoxin can have more than one sextillion(1021) stereoisomers! This staggering molecular complexity should indicate the difficult nature of designing a stereocontrolled synthetic strategy that will produce just the one correct (natural) stereocenter out of >1021 possible stereoisomers (Kishi did).

The Palythoa toxica species has more recently been found near Tahiti, but produces a slightly different compound. The Tahitian organism is not widely dispersed in the coral reefs off Tahiti, but does not appear to be as localized as it is on Maui (a single tidal pool).

[bradarmi]

Wow, that was interesting. Pharmacognasy and pharmacology will continue to develop as long as we are observant like Scheuer was. Nice article.

[lgreen]

interesting.

 

It appears from further reading, that specifically what happens is Palytoxin binds to the Na+/K+ protein pump comprimising the ion pathway.

 

so, yah, that's kind of deadly!

 

(and now my attempt based on my knowledge of cell biology to get a cause of death)

 

So therefore, there is an inbalance of movement of Na+ out of the cell and K+ into the cell. As the sodium concentration increases, water follows, causing the cell to swell. The swelling exapnds the cell membrane and increases porosity. Calcium ions (and many others) therefore rush in (keep in mind calcium outside of cell is 10000x more than inside) and activate all sorts of enzymes and endonucleases which basically eat the cell alive. Resulting in cause of cell death being necrosis. Then if concentrations of Palytoxin are high enough, tissue necrosis, and then organ necrosis, and then death.

 

fun stuff.

[onthefly]

Could also deregulate muscular/neuronal "firing" and induce a "seizure-like" state in the musculature (ala the vasoconstriction)....causing death. Sort of the opposite to Bungrotoxin (cobra venom).

 

Lgreen's the "healer" not me

[lgreen]

yep. the influx of Na+/K+ ions caused by the toxin messes with the depolarization and action potential which could mess with the neuro/muscular system.

 

yah, said something about coronary spasms...

 

After reading about it on some medical website, it seems to say basically the cause of death would be vasoconstriction and destruction of red blood cells leading to suffication

 

I'm not sure though if the vasoconstriction would be caused by cardiomyocyte death/disfunction or what you where talking about with neuro/muscular though.

 

that's amazing though that it only takes 4-5 micrograms of the toxin though to kill a human!

[onthefly]

Yeah...that's about 10x less than botulinum toxin!

 

As a undergrad, I worked on the AcH receptor and used Bungrotoxin and D-Tubocurarine....cuz the chicks dig biological agents

[dhoffroad]

so basicly when your walkin on the beach in Hawaii don't pick up some red seaweed stuff and chew on it...go for the green...right?...LOL...

 

sorry guys but you lost me way in the begining of this....LOL

[lgreen]

lol

 

actually i think the point would be, when your walking down the beach in Hawaii, dont lick or eat zoanthids

[klagos]

It took me a long time just to read this thread. I can't begin to imagine how long it is going to take me to look up all them big words. Thanks for the info.

[onthefly]

"I'll take useless random trivia for $1000 Alex..." Story of my life:)

 

When My wife and I went to Maui last summer I was at Hana.....Didn't dive because of all the "big shark" signs.....more worries about them then some silly LD50 of 5ug

[NepTuNe-UsD]

So basically the flux capacitor engine of the DeLorean species can fire energy pulses potent enough to cause a ripple in the space time continuum. Veeeery Interesting...

[Caesar777]

Heheh.. My only point was that it's a single species (and possibly a Tahitian subspecies) which possess the Palytoxin... See what hype does? I'll still be careful with my zoas, but they're obviously NOT Palythoa toxica--considering that, again, it's been found only in one 50-gallon (edit: 150 gallons; whatever) pool--so people are making, well, much ado about nothing.

[lgreen]

ah,

 

missed that detail.

 

my mind gravitates to the medical/cellular/molecular issues, not the population/ecology/distribution boring garbage stuff

[Caesar777]

Hehe... To each his own.

[NepTuNe-UsD]

Originally posted by Caesar777

Heheh.. My only point was that it's a single species (and possibly a Tahitian subspecies) which possess the Palytoxin... See what hype does?

 

Or possibly a single species that possess a palytoxin of that potency. It may be psychosomatic or just misdiagnosis but Ive read threads on reef central about people getting sick after handling zoanthids, but nothing lethal.

[Caesar777]

Excellent point, Neptune.

[NowSnow]

and to think people inject these types of molecules all the time into their faces. Botox works basically the same way by inhibiting ion channels in the cell membrane. We've been talking about ion channel and gpcr inhibitors in my drug discovery class so its cool to see what i learn in school actually going on in nature.

[lgreen]

Originally posted by NepTuNe-UsD

Or possibly a single species that possess a palytoxin of that potency. It may be psychosomatic or just misdiagnosis but Ive read threads on reef central about people getting sick after handling zoanthids, but nothing lethal.

 

it's called emotional contagion (the copycat effect)

 

basically monkey see, monkey see self emotional benefit such as attention, monkey do even at expense of other monkeys emotions

 

neat stuff

 

and then you have your hypochondriacs...

[lgreen]

Originally posted by NowSnow

and to think people inject these types of molecules all the time into their faces.  Botox works basically the same way by inhibiting ion channels in the cell membrane.  We've been talking about ion channel and gpcr inhibitors in my drug discovery class so its cool to see what i learn in school actually going on in nature.

 

cool stuff huh

 

its always fun when people want to stick derivatives of deadly bacteria and viruses in their body to look pretty

 

at least if something goes wrong, i guess they will look pretty in their casket

[Caesar777]

lgreen - THANK you! So many people don't realize that. Honestly, most don't realize the power of their own minds. You can cause yourself pain, you can heal your own pain, and you can cause or cure a myriad of different "diseases" you might not even have. Chronic pains, fatigue problems, "stomach problems", etc., are sometimes caused by real factors (poor blood flow, chemical imbalances, etc.) but it's extremely often that people are causing it themselves without even realizing it. That's why placebos can be so useful. Heck, just look at that naturopathic craze that happened. Placeeebo.

[MrAnderson]

Actually to truly settle the question of which species is how toxic, we need some volunteers...

 

maybe some cats or something...?

[lgreen]

we could just grind up zoanthids and tell people it is meth...

 

they would be all over it.

[dhoffroad]

LOL...here kitty kitty...LOL

 

LOL...here tweeker tweeker...LOL

[onthefly]

Originally posted by NowSnow

gpcr inhibitors

 

Ahhh............pertussis toxin!

 

You know my PhD is on viral chemokines and GPCRs

 

I dabble in toxins though......

[onthefly]

Originally posted by lgreen

we could just grind up zoanthids and tell people it is meth...

 

That would solve the meth problem in Oregon!!! It's a better way than passing laws requiring a script for actifed.....idiot law makers!