Guanitoxin (GNT), formerly known as anatoxin-a(S) "Salivary"[a],[1] is a naturally occurring cyanotoxin commonly isolated from cyanobacteria (specifically of the genus Anabaena) and causes excess salivation in mammals via inhibition of acetylcholinesterase. Guanitoxin was first structurally characterized in 1989, and consists of a cyclic N-hydroxyguanine organophosphate with a phosphate ester moiety.[2]
The main mechanism of action for guanitoxin is by irreversibly inhibiting the active site of acetylcholinesterase leading to excess acetylcholine in the parasympathetic and peripheral nervous systems; inducing poisoning via nicotinic and muscarinic cholinergic receptor stimulation.[3] The clinical signs of high level guanitoxin exposure consists mainly of excessive salivation, lacrimation, chromodacryorrhea (in rats), urinary incontinence, muscular weakness, muscle twitching, convulsion, including opisthotonus, and respiratory distress and/or failure.[4][5]
Treatment of afflicted case by atropine has attested to suppress the muscarinic mediated toxicity; which prevents the namesake salivation that similarly reacts to prevent the toxin's other poisoning symptoms which include lacrimation, urinary incontinence and defecation. Atropine will not, however, counter another mechanism of the compounds toxicity as it also mediates a nicotinic adverse toxicity affecting muscle tremors, fasciculation, convulsions and respiratory failure.[citation needed]
Stability and degradation
Guanitoxin is generally labile. It decomposes rapidly in basic solutions, but is relatively stable in neutral or acidic solutions (pH 3-5). When stored at -20˚C, it slowly undergoes hydrolysis giving (5S)-5-[(dimethylamino)methyl]-2-imino-1-imidazolidinol and monomethyl-phosphate, and more slowly, formation of (S)-1-(2-iminoimidazolidin-4-yl)-N,N-dimethylmethanamine. Furthemore, air evaporation of guanitoxin resulted in significant hydrolysis to (5S)-5-[(dimethylamino)methyl]-2-imino-1-imidazolidinol.[2]
Scheme for guanitoxin degradation. Major microspecies at pH 7.4 are shown.
See also
Anatoxin-a – a cyanotoxin that shares some clinical exposure signs, and also relates to the same cyanobacteria genera, but with a different chemical structure and toxic mechanism of action
Paraoxon – A synthetic pesticide with an analogous mechanism of action
References
^Fiore, Marli Fátima; de Lima, Stella Thomaz; Carmichael, Wayne W.; McKinnie, Shaun M.K.; Chekan, Jonathan R.; Moore, Bradley S. (2020). "Guanitoxin, re-naming a cyanobacterial organophosphate toxin". Harmful Algae. Elsevier BV. 92: 101737. doi:10.1016/j.hal.2019.101737. ISSN 1568-9883. PMID 32113603.
^ abMatsunaga, Shigeki; Moore, Richard E.; Niemczura, Walter P.; Carmichael, Wayne W. (1989). "Anatoxin-a(s), a potent anticholinesterase from Anabaena flos-aquae". Journal of the American Chemical Society. American Chemical Society (ACS). 111 (20): 8021–8023. doi:10.1021/ja00202a057. ISSN 0002-7863.
^Hyde, E. G.; Carmichael, W. W. (1991). "Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7)". Journal of Biochemical Toxicology. 6 (3): 195–201. doi:10.1002/jbt.2570060305. PMID 1770503.
^Mahmood, Nik A.; Carmichael, Wayne W. (1986). "The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17". Toxicon. Elsevier BV. 24 (5): 425–434. doi:10.1016/0041-0101(86)90074-7. ISSN 0041-0101. PMID 3087030.
^Fernandes, Kelly; Ferraz, Humberto; Vereau, Fanny; Pinto, Ernani (2020-11-19). "Availability of Guanitoxin in Water Samples Containing Sphaerospermopsis torques-reginae Cells Submitted to Dissolution Tests". Pharmaceuticals. MDPI AG. 13 (11): 402. doi:10.3390/ph13110402. ISSN 1424-8247. PMC7699232. PMID 33227987.
^(The "(S)" its name stands for 'salivary' indicating its manner of affliction to distinguish it from a toxin having otherwise the same conventional name. cf. "See also" for aforementioned compound of shared nomenclature.)
January 07, 2023
guanitoxin, formerly, known, anatoxin, salivary, naturally, occurring, cyanotoxin, commonly, isolated, from, cyanobacteria, specifically, genus, anabaena, causes, excess, salivation, mammals, inhibition, acetylcholinesterase, first, structurally, characterized. Guanitoxin GNT formerly known as anatoxin a S Salivary a 1 is a naturally occurring cyanotoxin commonly isolated from cyanobacteria specifically of the genus Anabaena and causes excess salivation in mammals via inhibition of acetylcholinesterase Guanitoxin was first structurally characterized in 1989 and consists of a cyclic N hydroxyguanine organophosphate with a phosphate ester moiety 2 Guanitoxin NamesIUPAC name 5S 5 Dimethylamino methyl 1 hydroxy methoxy phosphoryl oxy 4 5 dihydro 1H imidazol 2 amineIdentifiersCAS Number 103170 78 13D model JSmol Interactive imageChemSpider 102921KEGG C19998PubChem CID 114989UNII 4258P76E76CompTox Dashboard EPA DTXSID20897217InChI InChI 1S C7H17N4O4P c1 10 2 5 6 4 9 7 8 11 6 15 16 12 13 14 3 h6H 4 5H2 1 3H3 H2 8 9 H 12 13 t6 m1 s1Key FYXHGVMFJYHPFX ZCFIWIBFSA NSMILES CN C C C H 1CN C N1OP O O OC NPropertiesChemical formula C 7H 17N 4O 4PMolar mass 252 211 g mol 1Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references Contents 1 Toxicity and treatment 2 Stability and degradation 3 See also 4 ReferencesToxicity and treatment EditThe main mechanism of action for guanitoxin is by irreversibly inhibiting the active site of acetylcholinesterase leading to excess acetylcholine in the parasympathetic and peripheral nervous systems inducing poisoning via nicotinic and muscarinic cholinergic receptor stimulation 3 The clinical signs of high level guanitoxin exposure consists mainly of excessive salivation lacrimation chromodacryorrhea in rats urinary incontinence muscular weakness muscle twitching convulsion including opisthotonus and respiratory distress and or failure 4 5 Treatment of afflicted case by atropine has attested to suppress the muscarinic mediated toxicity which prevents the namesake salivation that similarly reacts to prevent the toxin s other poisoning symptoms which include lacrimation urinary incontinence and defecation Atropine will not however counter another mechanism of the compounds toxicity as it also mediates a nicotinic adverse toxicity affecting muscle tremors fasciculation convulsions and respiratory failure citation needed Stability and degradation EditGuanitoxin is generally labile It decomposes rapidly in basic solutions but is relatively stable in neutral or acidic solutions pH 3 5 When stored at 20 C it slowly undergoes hydrolysis giving 5S 5 dimethylamino methyl 2 imino 1 imidazolidinol and monomethyl phosphate and more slowly formation of S 1 2 iminoimidazolidin 4 yl N N dimethylmethanamine Furthemore air evaporation of guanitoxin resulted in significant hydrolysis to 5S 5 dimethylamino methyl 2 imino 1 imidazolidinol 2 Scheme for guanitoxin degradation Major microspecies at pH 7 4 are shown See also EditAnatoxin a a cyanotoxin that shares some clinical exposure signs and also relates to the same cyanobacteria genera but with a different chemical structure and toxic mechanism of action Paraoxon A synthetic pesticide with an analogous mechanism of actionReferences Edit Fiore Marli Fatima de Lima Stella Thomaz Carmichael Wayne W McKinnie Shaun M K Chekan Jonathan R Moore Bradley S 2020 Guanitoxin re naming a cyanobacterial organophosphate toxin Harmful Algae Elsevier BV 92 101737 doi 10 1016 j hal 2019 101737 ISSN 1568 9883 PMID 32113603 a b Matsunaga Shigeki Moore Richard E Niemczura Walter P Carmichael Wayne W 1989 Anatoxin a s a potent anticholinesterase from Anabaena flos aquae Journal of the American Chemical Society American Chemical Society ACS 111 20 8021 8023 doi 10 1021 ja00202a057 ISSN 0002 7863 Hyde E G Carmichael W W 1991 Anatoxin a s a naturally occurring organophosphate is an irreversible active site directed inhibitor of acetylcholinesterase EC 3 1 1 7 Journal of Biochemical Toxicology 6 3 195 201 doi 10 1002 jbt 2570060305 PMID 1770503 Mahmood Nik A Carmichael Wayne W 1986 The pharmacology of anatoxin a s a neurotoxin produced by the freshwater cyanobacterium Anabaena flos aquae NRC 525 17 Toxicon Elsevier BV 24 5 425 434 doi 10 1016 0041 0101 86 90074 7 ISSN 0041 0101 PMID 3087030 Fernandes Kelly Ferraz Humberto Vereau Fanny Pinto Ernani 2020 11 19 Availability of Guanitoxin in Water Samples Containing Sphaerospermopsis torques reginae Cells Submitted to Dissolution Tests Pharmaceuticals MDPI AG 13 11 402 doi 10 3390 ph13110402 ISSN 1424 8247 PMC 7699232 PMID 33227987 The S its name stands for salivary indicating its manner of affliction to distinguish it from a toxin having otherwise the same conventional name cf See also for aforementioned compound of shared nomenclature Retrieved from https en wikipedia org w index php title Guanitoxin amp oldid 1039856257, wikipedia, wiki, book, books, library,
