199
12
Saxitoxin and its analogues neosaxitoxin and gonyautoxin are known as paralytic shellfish toxins, which are strong and selective voltage-gated sodium channel (Na v Ch) blockers due to the guanidinium groups. These molecules are found in many species of marine
dinoflagellates and several freshwater species of cyanobacteria, and they can accumulate
in mussels, leading to intoxication of humans. Propionyl-ACP is fused with arginine,
and after several steps and cyclizations, saxitoxin is synthesized. This leads to a reduced
purine ring system, which is not biosynthetically related to the purine alkaloids. Arginine
is also a precursor for tetrodotoxin, another neurotoxin, which selectively inhibits voltage-gated Na + -channels and thus blocks the propagation of action potentials. It contains
a polar guanidino group, probably coupled to an isopentenyl diphosphate. Tetrodotoxins
occur mainly in macrozoa, particularly among puffer fish, several species of marine
invertebrates and a few terrestrial amphibians. This toxin makes also the Japanese dish
“fugu” sometimes lethal. It is discussed that the primary source of tetrodotoxin in these
animals are marine bacteria taken up with food or via symbiosis (Lago et al. 2015).
12.17 Kainoids
Several types of kainoids exist that vary within their side groups, kainic acid (kainate),
domoic acid and acromelic acid are the most prominent natural occurring forms. Domoic
acid is produced by diatoms (esp. Pseudo-nitzschia sp.) or the alga Chondria armata and
accumulates in mollusks and other marine animals causing amnesic shellfish poisoning
in humans. It is formed from the condensation of GPP (see above, 7 Sect. 10.1) with
glutamate to generate a pyrrolidine ring skeleton by cyclization that is subsequently converted to domoic acid (Savage et al. 2012). The toxin acts as an agonist of the ionotropic
kainite glutamate receptor and is excitotoxic in the vertebrate central nervous system
and other glutamate receptor-rich organs. Kainic acid, which is even more potent, differs
from domoic acid by one side chain and is isolated from the red alga Digenea simplex.
Acromelic acid is the toxic component of the mushroom Clitocybe acromelalga.
References
Al Balkhi MH, Schiltz S, Lesur D, Lanoue A, Wadouachi A, Boitel-Conti M (2012) Norlittorine and norhyoscyamine identified as products of littorine and hyoscyamine metabolism by (13)C-labeling in
Datura innoxia hairy roots. Phytochemistry 74:105–114. https://doi.org/10.1016/j.phytochem.2011.
10.010
Take Home Messages
5 Alkaloids always contain a nitrogen atom, usually within a heterocyclic ring.
5 They are mainly synthetized from aromatic amino acids (Phe, Tyr, Trp) but also
some other amino acids, ornithine, spermidine, xanthosine and the terpenoids.
5 Many toxic components are present within this group and many have shown
to interact with mammalian receptors or channels such as ibogaine, psilocybin,
morphine, codeine, bicuculline, mescaline, acreoline, atropine, cocaine, caffeine,
cytisine, aconitine, anatoxin A, muscimol, guanidinium toxins and kainoids.
5 Not only many plants synthetize alkaloids, but also some algae, diatoms and
mushrooms are able to produce them. Alkaloids found in animals are often
taken up by their diet.
References
12
Saxitoxin and its analogues neosaxitoxin and gonyautoxin are known as paralytic shellfish toxins, which are strong and selective voltage-gated sodium channel (Na v Ch) blockers due to the guanidinium groups. These molecules are found in many species of marine
dinoflagellates and several freshwater species of cyanobacteria, and they can accumulate
in mussels, leading to intoxication of humans. Propionyl-ACP is fused with arginine,
and after several steps and cyclizations, saxitoxin is synthesized. This leads to a reduced
purine ring system, which is not biosynthetically related to the purine alkaloids. Arginine
is also a precursor for tetrodotoxin, another neurotoxin, which selectively inhibits voltage-gated Na + -channels and thus blocks the propagation of action potentials. It contains
a polar guanidino group, probably coupled to an isopentenyl diphosphate. Tetrodotoxins
occur mainly in macrozoa, particularly among puffer fish, several species of marine
invertebrates and a few terrestrial amphibians. This toxin makes also the Japanese dish
“fugu” sometimes lethal. It is discussed that the primary source of tetrodotoxin in these
animals are marine bacteria taken up with food or via symbiosis (Lago et al. 2015).
12.17 Kainoids
Several types of kainoids exist that vary within their side groups, kainic acid (kainate),
domoic acid and acromelic acid are the most prominent natural occurring forms. Domoic
acid is produced by diatoms (esp. Pseudo-nitzschia sp.) or the alga Chondria armata and
accumulates in mollusks and other marine animals causing amnesic shellfish poisoning
in humans. It is formed from the condensation of GPP (see above, 7 Sect. 10.1) with
glutamate to generate a pyrrolidine ring skeleton by cyclization that is subsequently converted to domoic acid (Savage et al. 2012). The toxin acts as an agonist of the ionotropic
kainite glutamate receptor and is excitotoxic in the vertebrate central nervous system
and other glutamate receptor-rich organs. Kainic acid, which is even more potent, differs
from domoic acid by one side chain and is isolated from the red alga Digenea simplex.
Acromelic acid is the toxic component of the mushroom Clitocybe acromelalga.
References
Al Balkhi MH, Schiltz S, Lesur D, Lanoue A, Wadouachi A, Boitel-Conti M (2012) Norlittorine and norhyoscyamine identified as products of littorine and hyoscyamine metabolism by (13)C-labeling in
Datura innoxia hairy roots. Phytochemistry 74:105–114. https://doi.org/10.1016/j.phytochem.2011.
10.010
Take Home Messages
5 Alkaloids always contain a nitrogen atom, usually within a heterocyclic ring.
5 They are mainly synthetized from aromatic amino acids (Phe, Tyr, Trp) but also
some other amino acids, ornithine, spermidine, xanthosine and the terpenoids.
5 Many toxic components are present within this group and many have shown
to interact with mammalian receptors or channels such as ibogaine, psilocybin,
morphine, codeine, bicuculline, mescaline, acreoline, atropine, cocaine, caffeine,
cytisine, aconitine, anatoxin A, muscimol, guanidinium toxins and kainoids.
5 Not only many plants synthetize alkaloids, but also some algae, diatoms and
mushrooms are able to produce them. Alkaloids found in animals are often
taken up by their diet.
References