Tetrodotoksin

Tetrodotoksin
Nazivi
	IUPAC naziv 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 broj	4368-28-9 ;
3D model (Jmol)	interaktivna slika;
ChemSpider	9349691 ;
ECHA InfoCard	100.022.236
KEGG	C11692 ;
PubChem C ID	11174599;
	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 Ključ: 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 Ključ: CFMYXEVWODSLAX-QOZOJKKEBM;
	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; ; ; ; ; ;
Svojstva
Hemijska formula	C11H17N3O8
Molarna masa	319,268
	Ukoliko nije drugačije napomenuto, podaci se odnose na standardno stanje materijala (na 25°C [77°F], 100 kPa).
	Reference infokutije

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.^[4] Grupa japanskih istraživača je veštački sintetizovala tetrodotoksin 1972. godine.^[5]^[6]

Delovanje

Tetrodotoksin blokira provođenje nervnog impulsa duž aksona i u nadražljivim membranama nervnih vlakana, što dovodi do paralize respiratornih mišića i prekida disanja.^[7]

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.^[7]

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.^[7]

Osobine

Osobina	Vrednost
Broj akceptora vodonika	9
Broj donora vodonika	9
Broj rotacionih veza	1
Particioni koeficijent^[8] (ALogP)	-4,0
Rastvorljivost^[9] (logS, log(mol/L))	2,3
Polarna površina^[10] (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.^[11]

Izvori

^ 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.
^ 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. PMID 20970519. doi:10.1016/j.drudis.2010.10.003. uredi
^ 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.
^ 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 11. 08. 2011. g. Pristupljeno 12. 8. 2008.
^ Kishi Y, Aratani M, Fukuyama T, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (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. PMID 4642370. doi:10.1021/ja00781a038.
^ 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. PMID 4642371. doi:10.1021/ja00781a039.
^ ^a ^b ^v Strajer, L. 1991. Biokemija. Školska knjiga: Zagreb.
^ Ghose, A.K.; Viswanadhan V.N. & 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. PMID 11749573. doi:10.1021/ci000392t.
^ 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. PMID 11020286. doi:10.1021/jm000942e.
^ Anderson WH (1988). „Tetrodotoxin and the zombi phenomenon”. Journal of Ethnopharmacology. 23 (1): 121—6. PMID 3419200. doi:10.1016/0378-8741(88)90122-5.

Literatura

Clayden, Jonathan; Greeves, Nick; Warren, Stuart; Wothers, Peter (2001). Organic Chemistry (I izd.). Oxford University Press. ISBN 978-0-19-850346-0.
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 (Second izd.). Academic Press. ISBN 0080429882.

Spoljašnje veze

Tetrodotoxin: essential data (1999)
Tetrodotoxin from the Bad Bug Book at the U.S. Food and Drug Administration website

[1] 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.

[2] 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. PMID 20970519. doi:10.1016/j.drudis.2010.10.003. uredi

[3] 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.

[4] 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 11. 08. 2011. g. Pristupljeno 12. 8. 2008.

[5] Kishi Y, Aratani M, Fukuyama T, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (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. PMID 4642370. doi:10.1021/ja00781a038.

[6] 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. PMID 4642371. doi:10.1021/ja00781a039.

[стр-7] v Strajer, L. 1991. Biokemija. Školska knjiga: Zagreb.

[8] Ghose, A.K.; Viswanadhan V.N. & 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.

[9] 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. PMID 11749573. doi:10.1021/ci000392t.

[10] 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. PMID 11020286. doi:10.1021/jm000942e.

[pmid3419200-11] Anderson WH (1988). „Tetrodotoxin and the zombi phenomenon”. Journal of Ethnopharmacology. 23 (1): 121—6. PMID 3419200. doi:10.1016/0378-8741(88)90122-5.

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