Increasing evidence are indicative that puffer fish do not have the genes coding for a
pathway for the synthesis tetrodotoxin molecules. David Berkowitz
and Ilona Kryspin-Sorensen have reviewed some of this evidence in a publication entitled
"Transgenic Fish: Safe to Eat". Some of the points raised follow.
Puffer fish grown in culture do not produce tetrodotoxin
until they are fed tissues from a toxin producing fish.
The blue-ringed octopus found in Australian waters accummulates tetrodotoxin
in a special salivary glad and infuses its prey with toxin by bite.
This octopus contains tetrodotoxin-producing bacteria.
Xanthid crabs collected from the same waters contain tetrodotoxin and paralytic shellfish toxin.
Tetrodotoxin in algae species Jania is produced by a bacteria
species Alteromas.
Additionally, tetrodotoxin is similar in structure and mode of
action to saxitoxin
which is a neurotoxin produced by
a marine micro-organism.
Both tetrodotoxin and saxitoxin inhibit the activity of the
voltage sensitive sodium channel in the same mode of action;
and both molecules contain a guanidinium moiety.
3D-Structure of Tetrodotoxin
The structure of a hydrobromide derivative of
tetrodotoxin (C11 H17 N3 O8.HBr) was determined to atomic resolution, by Akio Furusaki and co-workers from the Faculty of Science, Kwansei Gakuin University, Nishinomiya, using three-dimensional X-ray analysis.The coordinate dataset was obtained from the
Cambridge Crystallographic Data Centre.
Another 3D representation of
tetrodotoxin is also shown. Tetrodotoxin is also known as anhydrotetrodotoxin, 4-epitetrodotoxin and tetrodonic acid.
Mode of Action of Tetrodotoxin
Tetrodotoxin is one of the most potent molecules known to selectively block
the voltage-sensitive sodium channels of excitable tissues.
As a result, tetrodotoxin inhibits or reduces the chances of an action
potential to be produced. Tetrodotoxin is complex in structure by small
molecule standards and contains a guanidinium moiety.
The guanidinium ion is able to enter cells via the voltage sensitive
Na+ channels. It is likely that this imidazole ring is the part of the molecule
that lodges in the channel leaving the rest of the molecule blocking its
outer mouth. Their association and disscociation are independent of whether
the channel is open or closed.
Puffer Fish Resistance to Tetrodotoxin
The Puffer fish has a mutation in the protein sequence of the sodium channel pump found on the cell membranes, this
sodium channel is critical for cellullar signalling pathways (e.g. transmission of impulses and the mediation of many cell
functions). This point mutation in the amino-acid sequence compared to the sequence in man makes these fish highly
resistant to tetradotoxin poisoning, as a result tetradotoxin does not recognise the channel in pufferfish and therefore
does not bind to it and block it. The puffer fish store high concentrations of tetratodoxin in various organs. However, the
species differ widely in terms their resistance to tetradotoxin.
