The Chemistry of Fugu Fish Toxins


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Fugu is the Japanese word for Pufferfish and the name of the dish prepared with it. Although it is considered a delicacy and is one of the most celebrated and popular dishes in Japanese culture, fugu can be fatally poisonous because of its tetrodotoxin. The dish must be carefully prepared and cleaned of toxic parts that would contaminate the meat. Restaurant preparation of fugu is stringently controlled by law in Japan and several other countries. Chefs must be qualified and have three or more years of rigorous training to be allowed a licence to prepare the dish for customers. The dish is served as sashimi and chirinabe, two different types of sushi. People in Japan consume 10,000 tons of the fish on average per year. A dish of fugu commonly costs between ¥2,000 (approx. US$20) and ¥5,000 (approx. US$50); a full-course fugu meal (usually eight servings) can cost ¥10,000–20,000 (approx. US$100–200). Domestic preparation occasionally leads to accidental death. Some people consider the liver the most savory part, but it’s also the most toxic part. Serving the liver was eventually banned in restaurants in Japan in 1984. Yearly, there are 20-40 cases of poisoning due to the fugu fish.

Tetrodotoxin is the toxin found most commonly in the liver and sex organs of certain species of tropical and subtropical fish. These species of fish have been named Tetraodontiformes. These fish include: pufferfish, porcupinefish, ocean sunfish, and triggerfish, with pufferfish being the most popular for consumption. Tetrodotoxin was originally discovered in these fish and is produced by certain infecting or symbiotic bacteria like Pseudoalteromonas, Pseudomonas, Vibrio as well as other species found in these animals. Tetrodotoxin can be up to 1,200 times more poisonous than cyanide. There is enough toxin in one pufferfish to kill 30 adult humans, and there is no known antidote.

Biologists believe that pufferfish, also known as blowfish, refined their reputable “inflatability” because their dawdling, considerably ungainly swimming style renders them defenseless to predators. Instead of escape, pufferfish use their highly elastic stomachs and their ability to quickly inhale huge amounts of water (and even air when necessary) to turn themselves into an essentially inedible ball several times their normal size. Some species also have spines on their skin to make them even less pleasant. There are more than 120 species of pufferfish worldwide and most of them are found in tropical and subtropical ocean waters, but some species live in salty and fresh water. Pufferfish range in size from the 1-inch-long dwarf or pygmy puffer to the freshwater giant puffer, which can grow to more than 2 feet in length. They are scaleless fish and typically have rough and spiky flesh. All of these species have four teeth that are fused together into a beak-like shape. The diet of pufferfish includes mostly invertebrates and algae. Larger species will often crack open and eat clams, mussels, and shellfish with their hard beaks. Some species of pufferfish have been considered vulnerable due to pollution, habitat loss, and overfishing, but most populations are considered stable.

Although this topic may seem boring or uninteresting to some people, I enjoy learning about aquatic creatures and how they defend themselves and procreate in their natural habitats. When I was about ten I was watching a show called Total Drama Island. There were some contestants that were given a fish and a diagram. They were told that they had to prepare this fish for their partner and if they did it wrong their partner would die. This was already intriguing to ten-year-old me, but when I found out that this fish was real and people actually paid to eat this poisonous fish I was amazed. When I heard we were doing this project I was a little panicked, but I ended up searching “crazy foods around the world”. The fugu fish was one of the first results to come up and I was instantly inspired and excited. The fugu fish has never directly affected me or my family, but I have convinced myself that I am superior to my peers for having educated myself on the aquatic lifestyles of the fugu fish and the cuttlefish.

Composition of ...

  • Chemical Formula: C 11 H 17 N 3 O 8 (TTX)

  • Chemical Formula: C 408 H 674 N 126 O 126 S 2 (PTH)

Main Chemicals, Compounds, Components

  • Tetrodotoxin (TTX): C 11 H 17 N 3 O 8

Tetrodotoxin binds to Site 1 of the fast voltage-gated sodium channel. Site 1 is found at the extracellular pore opening of the ion channel and blocks the passing of sodium ions into the nerve cell (which is necessary for nerve conduction). The use of Tetrodotoxin as a biochemical probe has shed light on two easily distinguishable types of voltage-gated sodium channels present in humans: the tetrodotoxin-sensitive voltage-gated sodium channel (TTX-s Na+ channel) and the tetrodotoxin-resistant voltage-gated sodium channel (TTX-r Na+).

  • Parathyroid hormone (PTH): C 408 H 674 N 126 O 126 S 2

In 2003 a PTH gene was isolated from the Fugu fish. Parathyroid hormone (AKA parathormone or parathyrin) is a hormone secreted by the parathyroid glands that is a major actor in bone remodeling, which is a continuing process in which bone tissue is alternately resorbed and rebuilt over time. It pretty much increases blood calcium levels. The bones act as a “calcium bank” from which the body can make “withdrawals” when needed to keep the amount of calcium in the blood at appropriate levels even when faced with the recurrent challenges of metabolism, stress, and nutritional variations. PTH is considered a “key that unlocks the bank vault” to release calcium.

Chemistry's Role


Tetrodotoxin binds to TTX-s Na+ channels with a binding affinity of 5-15 nM (nanometers), but the TTX-r Na+ channels bind TTX with low micromolar affinity. A binding affinity is a measure of the strength of attraction between a receptor and its counterpart. Therefore, the binding affinity between TTX and TTX-r Na+ channels is less than or weaker than the affinity between TTX and TTX-s Na+ channels. This is important because the affinities are the distinguishable factors between these channels. Nerve cells holding TTX-r Na+ channels are located predominantly in cardiac tissue, while nerve cells containing TTX-s Na+ channels influence the rest of the body. TTX and its analogs have historically been important agents for use as chemical tool compounds, for use in channel characterization and in fundamental studies of channel function. The prevalence of TTX-s Na+ channels in the central nervous system makes tetrodotoxin a valuable agent for the silencing of neural activity within a cell culture.


PTH is held by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids, which makes it a prohormone. While PTH acts to increase the concentration of ionic calcium in the blood, calcitonin (a hormone produced by the parafollicular cells of the thyroid gland) acts to decrease ionic calcium concentration. PTH essentially acts to increase the concentration of calcium in the blood by manipulating the parathyroid hormone 1 receptor (which is present at high levels of calcium in bones and kidneys) and the parathyroid hormone 2 receptor (which is present at high levels of calcium in the central nervous system, pancreas, testis, and placenta).


Background Research


Tetrodotoxin hinders the firing of action potentials in nerves by binding to the voltage-gated sodium channels in nerve cell membranes and blocking the passage of sodium ions into the nerve cells. Dawning symptoms of Tetrodotoxin intoxication usually transpires from 10 to 45 minutes after consumption, but can be postponed by 3 hours or more. Indications of Tetrodotoxin intoxication include: paraesthesia (tingling) appearing in the face and extremities, dizziness or numbness, nausea, vomiting, diarrhoea, and epigastric pain. This is soon followed by paralysis of voluntary muscles including the diaphragm and intercostal muscles, which then stops the breathing.


PTH is vital to health and health problems that create too little or too much PTH. Some of these health problems include: hypoparathyroidism, hyperparathyroidism, or paraneoplastic syndromes. These can negatively affect the body with bone disease, hypocalcaemia, and hypercalcaemia.



  • Information on fish habitat, lifestyle, and prices

  • Information on TTX and description

  • Info on TTX and how it works

  • Info on fugu prep and training

  • Info on fugu “inflatability”,28804,1967235_1967238_1967227,00.html

  • Fugu toxicity

  • Info on affinity receptors

  • PTH info and how it works

  • How PTH was isolated

  • Info on PTH

About the Author

Sarah Qualls is a junior at Senior High School in Billings, Montana. She enjoys learning about various aquatic creatures (pufferfish, cuttlefish, etc.) and how they defend themselves against predators. She hopes to become a Physician’s Assistant and is interested in Same Day Care. She is on the Senior swim team and has lettered in golf and orchestra. She plays the violin, string bass, piano, ukulele, and mandolin. She has two golden doodles and a chocolate point siamese with bright blue eyes. She also owns a sister who may or may not have helped with this project and has failed to pronounce “the end” on several occasions. Thus providing their family with an inside joke that will last for years to come.