Fugu for You?

              My husband’s birthday was a few weeks ago.  I told him we could go anywhere he wanted so he chose the most expensive place in the city.  Okay, sure.  It’s always a great meal and I get to eat well, too, so I’m definitely not complaining!  We went to the excellent restaurant Morimoto.  (And for you NYC readers, the Philly Morimoto came first.  So did the Philly Buddakan.  Stop stealing our restaurants.)

                Of course, being that Morimoto, which is owned by Iron Chef Masaharu Morimoto, is all Japanese food, we started the inevitable Japanese food conversation: Will we or won’t we try puffer fish when we travel to Japan.

                For anyone unfamiliar, puffer fish (or “fugu” in Japanese) is a meal prepared from one of several different kinds of fish (Figure 35.1) which have the poisonous tetrodotoxin within them.  Chefs must go through extensive training to learn how to prepare these fish (which includes removal of the most poisonous parts, such as the liver, ovary, skin, and intestine) and pass a comprehensive exam.  The regulations have to be this tight because tetrodotoxin has no known antidote.

         
               Obviously, a lot of deadly poisons exist in this world but they all don’t require the same amount of substance to kill you.  Sometimes you need 1 gram of your poison to kill but a different poison will only require 0.1 g.  Poisons are fun like that.  Scientists have developed a way to convey how poisonous something is with what is called an LD₅₀ or lethal dose, 50%.  I will explain what this means with the following example:

         

Let’s pretend you have ten people standing in a line 

that all weight 100 lbs, which is equal to 45 kg.

You start by feeding each of them 100 ug (microgram, 

see Slideshow Pictures – Microscopes and Photography post) 

of tetrodotoxin.   

Everyone is still standing there.

You then feed them another 100 ug, so everyone now has had 200 ug total of tetrodotoxin.   

One person dies but the other nine are still there.

Okay, good.

You then feed the remaining nine 250 ug of tetrodotoxin.   

Four more people die.

Here is where you stop and I asked you a question: 

How much tetrodotoxin must you feed a group of people in order to kill 50% of them?

The answer in this experiment was 450 ug (go back and count if you don’t believe me).   

Feeding 450 ug resulted in 5 out of 10 people dying.   

So, the LD₅₀ would be equal to 450 ug.

Since not everyone weighs the same thing, LD₅₀s are usually written as grams per unit weight.  In our example, everyone weighed 45 kg so it would be written as 450 ug/45 kg = 10 ug/kg.

The LD₅₀ for tetrodotoxin is 10 ug/kg or 0.00001 g/kg. Gosh, that’s a small amount!  Just for sake of comparison, the LD₅₀ for arsenic is 0.145 g/kg.  The LD₅₀ for botulism toxin is 0.000000003 g/kg.  (No LD₅₀ exists for iocane powder because… well, it doesn’t exist).

Let’s say you didn’t know any of this stuff and somehow came to catch a fugu and subsequently decide that you should definitely eat it.  What are you in for?  Well, dizziness, headache, nausea, difficulty breathing and exhaustion.  You will die from asphyxiation.  Tetrodotoxin, or TTX, is a neurotoxin that binds important sodium channels in our neurons (brain cells).  The structure of TTX can be seen in Figure 35.2.

Cells are enclosed by a plasma membrane (see CentralDogma post) in order to keep things out.  The plasma membrane is protecting the inside of the cell.  However, just as a with a walled-in city, some things still need to get inside!  Many molecules have helper proteins within the plasma membrane that facilitate their movement across the barrier.  These special proteins create tunnels in the membranes to allow things to pass.  In neurons, an important species that needs to pass is the sodium ion.  In response to certain stimuli in the brain, this action of sodium ions helps keep our brains working.  Sodium ions pass through proteins called voltage-gated sodium channels.

Unfortunately, if TTX is ingested, this small molecule will bind the voltage-gated sodium channels in our neurons and block them.  If sodium ions can’t pass through their channels, brain function stalls and we end up with all the lovely symptoms outlined above.  The voltage-gated ion channels in the pufferfish are slightly different than our own and, thus cannot bind TTX.  Their channels don’t become blocked - lucky ducks (err, fish).

Interestingly, TTX is not limited to pufferfish.  It is also found in salamanders, frogs, octopus, starfish, and a few types of crabs.  These animals do not make TTX, however.  Instead, it is the bacteria in their food supply which create the toxin.  It has been shown that if puffer fish are grown in an environment lacking these bacteria, then they will no longer have TTX in their system.

So, why would anyone eat this?  Why take the risk that the most poisonous parts may not have been removed before eating the fish?  Because those who have eaten it say it is wonderful.  Accordingly to Toshio Narahashi, “…puffer has long been regarded as one of the most delicious fish in Japan.”  My husband is all about trying it.  I am mostly all about trying it.  Whenever we do, I’ll gladly report back.

Microgram: 1 ug = 0.000001 g

REFERENCES

Narahashi, T. “Tetrodotoxin.” Proc. Jpn. Acad. Ser. B (2008) 84, pgs 147 – 154

Yu, F H and Catterall, W A. “Overview of the voltage-gated sodium channel family.” Genome Biology (2003) 4(3), pg 207

MSDS for Arsenic: http://www.sciencelab.com/msds.php?msdsId=9922970

LD₅₀ for Botulism: http://www.aahealth.org/physicianslink/bioterrorism_botulism_overview.asp

 

Photo for Japanese puffer fish: http://cmbi.bjmu.edu.cn/news/0110/109.htm