Tetrodotoksin

Tetrodotoksin
	Oktahidro-12-(hidroksimetil)-2-imino-5,9:7, 10a-dimetano-10aH-[1,3]dioksocino[6,5-d] pirimidin-4,7,10,11,12-pentol
Drugi nazivi	anhidrotetrodotoksin, 4-epitetrodotokksin, tetrodonična kiselina, TTX
Identifikacija
CAS registarski broj	4368-28-9
PubChem	11174599
ChemSpider	9349691
KEGG	C11692
ChEMBL	CHEMBL507974
Jmol-3D slike	Slika 1
SMILES
	O1[C@@H]4[C@@](O)([C@@H]3O[C@@]1(O)[C@@H](O)[C@]2(N\C(=N/[C@H](O)[C@H]23)N)[C@@H]4O)CO
InChI
	InChI=1S/C11H17N3O8/c12-8-13-6(17)2-4-9(19,1-15)5-3(16)10(2,14-8)7(18)11(20,21-4)22-5/h2-7,15-20H,1H2,(H3,12,13,14)/t2-,3-,4-,5+,6-,7+,9+,10-,11+/m1/s1 ; Kod: CFMYXEVWODSLAX-QOZOJKKESA-N InChI=1/C11H17N3O8/c12-8-13-6(17)2-4-9(19,1-15)5-3(16)10(2,14-8)7(18)11(20,21-4)22-5/h2-7,15-20H,1H2,(H3,12,13,14)/t2-,3-,4-,5+,6-,7+,9+,10-,11+/m1/s1; Kod: CFMYXEVWODSLAX-QOZOJKKEBM
Svojstva
Molekulska formula	C11H17N3O8
Molarna masa	319.27 g mol−1
	; ; Ukoliko nije drugačije napomenuto, podaci se odnose na standardno stanje (25 °C, 100 kPa) materijala
	Infobox references

Tetrodotoksin je vrlo otrovno organsko jedinjenje u čiji sastav ulaze ugljenik, vodonik, kiseonik i azot. Nalazi se u ribi fugu (rod Diodon) koja pripada redu Tetraodontiformes, pa otuda i naziv ovog otrova.

Istorijat

Tetrodotoksin je otkrio japanski naučnik Tahara 1909. godine.^[6] Grupa japanskih istraživača je veštački sintetizovala tetrodotoksin 1972. godine.^[7]^[8]

Delovanje

Tetrodotoksin blokira provođenje nervnog impulsa duž aksona i u nadražljivim membranama nervnih vlakana, što dovodi do paralize respiratornih mišića i prekida disanja.^[9]

Mehanizam

Gvanidino grupa toksina stupa u interakciju sa negativno naelektrisanim karboksilatom na ulazu u kanal natrijuma sa spoljašnje strane ćelijske membrane. Ovaj otrov je u suštini kompeticijski inhibitor natrijumovih jona.^[9]

Značaj

Tetrodotoksin je vrlo korisno sredstvo u istraživanjima zbog visokog afiniteta za natrijumove kanale. Tako je, na primer, gustina natrijumovih kanala u raznim nadražljivim membranama određena merenjem količine vezanog radiokativno označenog tetrodotoksina. Tako se došlo do toga da su u nemijeliziranim nervnim vlaknima (koja nemaju mijelinski omotač) natrijumovi kanali veoma retki, za razliku od specijalizovanih područja mijeliziranih vlakana (tzv. Ranvijerovim čvorovima) gde ovi kanali zauzimaju veliki deo površine membrane.^[9]

Osobine

Osobina	Vrednost
Broj akceptora vodonika	9
Broj donora vodonika	9
Broj rotacionih veza	1
Particioni koeficijent^[10] (ALogP)	-4,0
Rastvorljivost^[11] (logS, log(mol/L))	2,3
Polarna površina^[12] (PSA, Å²)	187,7

Zanimljivost

U manjim dozama, ovaj otrov ne mora obavezno da bude smrtonosan. Navodno je omiljen u vudu-magiji gde se smatra ključnim sastojkom za stvaranje zombija.^[13]

Izvori

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Clark RF, Williams SR, Nordt SP, Manoguerra AS (1999). „A review of selected seafood poisonings”. Undersea Hyperb Med 26 (3): 175-84. PMID 10485519. Arhivirano iz originala na datum 2011-08-11. Pristupljeno 2008-08-12.
↑ Kishi Y, Aratani M, Fukuyama T, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (December 1972). „Synthetic studies on tetrodotoxin and related compounds. 3. A stereospecific synthesis of an equivalent of acetylated tetrodamine”. J. Am. Chem. Soc 94 (26): 9217-9. DOI:10.1021/ja00781a038. PMID 4642370.
↑ Kishi Y, Fukuyama T, Aratani M, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (1972). „Synthetic studies on tetrodotoxin and related compounds. IV. Stereospecific total syntheses of DL-tetrodotoxin”. J. Am. Chem. Soc 94 (26): 9219-9221. DOI:10.1021/ja00781a039. PMID 4642371.
↑ ^9,0 ^9,1 ^9,2 Strajer, L. 1991. Biokemija. Školska knjiga: Zagreb.
↑ Ghose, A.K., Viswanadhan V.N., and Wendoloski, J.J. (1998). „Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragment Methods: An Analysis of AlogP and CLogP Methods”. J. Phys. Chem. A 102: 3762-3772. DOI:10.1021/jp980230o.
↑ Tetko IV, Tanchuk VY, Kasheva TN, Villa AE. (2001). „Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices”. Chem Inf. Comput. Sci. 41: 1488-1493. DOI:10.1021/ci000392t. PMID 11749573.
↑ Ertl P., Rohde B., Selzer P. (2000). „Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties”. J. Med. Chem. 43: 3714-3717. DOI:10.1021/jm000942e. PMID 11020286.
↑ Anderson WH (1988). „Tetrodotoxin and the zombi phenomenon”. Journal of Ethnopharmacology 23 (1): 121-6. DOI:10.1016/0378-8741(88)90122-5. PMID 3419200.

Literatura

Clayden Jonathan, Nick Greeves, Stuart Warren, Peter Wothers (2001). Organic chemistry. Oxford, Oxfordshire: Oxford University Press. ISBN 0-19-850346-6.
Smith, Michael B.; March, Jerry (2007). Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th izd.). New York: Wiley-Interscience. ISBN 0-471-72091-7.
Katritzky A.R., Pozharskii A.F. (2000). Handbook of Heterocyclic Chemistry. Academic Press. ISBN 0080429882.

Vanjske veze

Portal Hemija

Tetrodotoxin: essential data (1999)
Tetrodotoxin Arhivirano 2013-03-08 na Wayback Machine-u from the Bad Bug Book at the U.S. Food and Drug Administration website

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[6] Clark RF, Williams SR, Nordt SP, Manoguerra AS (1999). „A review of selected seafood poisonings”. Undersea Hyperb Med 26 (3): 175-84. PMID 10485519. Arhivirano iz originala na datum 2011-08-11. Pristupljeno 2008-08-12.

[7] Kishi Y, Aratani M, Fukuyama T, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (December 1972). „Synthetic studies on tetrodotoxin and related compounds. 3. A stereospecific synthesis of an equivalent of acetylated tetrodamine”. J. Am. Chem. Soc 94 (26): 9217-9. DOI:10.1021/ja00781a038. PMID 4642370.

[8] Kishi Y, Fukuyama T, Aratani M, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (1972). „Synthetic studies on tetrodotoxin and related compounds. IV. Stereospecific total syntheses of DL-tetrodotoxin”. J. Am. Chem. Soc 94 (26): 9219-9221. DOI:10.1021/ja00781a039. PMID 4642371.

[стр-9] 9,0 ^9,1 ^9,2 Strajer, L. 1991. Biokemija. Školska knjiga: Zagreb.

[10] Ghose, A.K., Viswanadhan V.N., and Wendoloski, J.J. (1998). „Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragment Methods: An Analysis of AlogP and CLogP Methods”. J. Phys. Chem. A 102: 3762-3772. DOI:10.1021/jp980230o.

[11] Tetko IV, Tanchuk VY, Kasheva TN, Villa AE. (2001). „Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices”. Chem Inf. Comput. Sci. 41: 1488-1493. DOI:10.1021/ci000392t. PMID 11749573.

[12] Ertl P., Rohde B., Selzer P. (2000). „Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties”. J. Med. Chem. 43: 3714-3717. DOI:10.1021/jm000942e. PMID 11020286.

[pmid3419200-13] Anderson WH (1988). „Tetrodotoxin and the zombi phenomenon”. Journal of Ethnopharmacology 23 (1): 121-6. DOI:10.1016/0378-8741(88)90122-5. PMID 3419200.

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