刺尾魚毒素

刺尾魚毒素
	IUPAC名; Disodium (12S,14aR,15aS,16aR,17aS,18Z,110aR,111aS,112aR,113aS,114aR,116R,117R,118aS,119aR,121aS,122aR,123aS,124aR,125aS,126aR,127aS,22S,24aR,25aS,26aR,27aS,28aR,29aS,211R,212R,213aR,214S,214aS,215aR,217aS,218aR,219aS,32R,33R,34aS,36S,37R,38R,38aS,5R,7R,82S,83R,84aS,86R,87R,88R,88aS,92R,93R,94R,94aS,95aS,96aR,97aS,98R,99R,910S,911aR,912aS,913aR,914R,914aR,11S,12R,132S,133R,134S,134aS,135aR,136aS,137aR,138S,138aS,1310S,1311R,1312aR,1313aS,1314aR,1315aS,1317R,1317aR)-12-[(1S,2R,4R,5S)-1,2-dihydroxy-4,5-dimethyloct-7-en-1-yl]-117,211,214,33,37,38,5,7,83,87,88,93,94,98,914,11,12,133,134,138,1311,1317-docosahydroxy-14a,15a,16a,114a,116,119a,121a,122a,25a,27a,29a,214a,217a,1313a,1315a-pentadecamethyl-132-[(2R,3R,4R,7S,8R,9R,11R,13E)-3,8,11,15-tetrahydroxy-4,9,13-trimethyl-12-methylidene-7-(sulfonatooxy)pentadec-13-en-2-yl]-13,14,14a,15a,16,16a,17a,110,110a,111a,112,112a,113a,114,114a,116,117,118,118a,119a,120,121,121a,122a,123,123a,124a,125,125a,126a,127,127a,22,23,24,24a,25a,26,26a,27a,28,28a,29a,210,211,212,213a,214,214a,215a,216,217,217a,218a,219,219a,32,33,34,34a,36,37,38,38a,82,83,84,84a,86,87,88,88a,93,94,94a,95a,96,96a,97a,98,99,910,911a,912,912a,913a,914,914a,133,134,134a,135a,136,136a,137a,138,138a,1310,1311,1312,1312a,1313a,1314,1314a,1315a,1316,1317,1317a-octahectahydro-12H,92H,132H-1(16)-pyrano[2′′′ ′,3′′′ ′:5′′′,6′′′]pyrano[2′′′,3′′′:6′′,7′′]oxepino[2′′,3′′:5′,6′]pyrano[2′,3′:5,6]pyrano[3,2-b]pyrano[2′′′,3′′′:5′′,6′′]pyrano[2′′,3′′:5′,6′]pyrano[2′,3′:5,6]pyrano[2,3-g]oxocina-2(2,12)-bis(pyrano[2′′,3′′:5,6]pyrano[2′,3′:5,6]pyrano)[3,2-b:2′,3′-f]oxepina-13(10)-pyrano[3,2-b]pyrano[2′′′,3′′′:5′′,6′′]pyrano[2′′,3′′:5′,6′]pyrano[2′,3′:5,6]pyrano[2,3-f]oxepina-9(2,10)-dipyrano[2,3-e:2′,3′-e′]pyrano[3,2-b:5,6-b′]dipyrana-3,8(2,6)-bis(pyrano[3,2-b]pyrana)tridecaphan-99-yl sulfate
識別
CAS號	59392-53-9
ChemSpider	25991548
SMILES	C[C@H](CC[C@@H]([C@@H]([C@H](C)C[C@H](C(=C)/C(=C/CO)/C)O)O)OS(=O)(=O)[O-])[C@H]([C@@H](C)[C@H]1[C@@H]([C@@H]([C@H]2[C@H](O1)[C@@H](C[C@]3([C@H](O2)C[C@H]4[C@H](O3)C[C@]5([C@H](O4)[C@H]([C@H]6[C@H](O5)C[C@H]([C@H](O6)[C@@H]([C@H](C[C@H]7[C@@H]([C@@H]([C@H]8[C@H](O7)C[C@H]9[C@H](O8)C[C@H]1[C@H](O9)[C@H]([C@@H]2[C@@H](O1)[C@@H]([C@H]([C@@H](O2)[C@H]1[C@@H]([C@H]([C@H]2[C@@H](O1)C[C@H]([C@@H](O2)[C@@H](C[C@H](C[C@H]1[C@@H]([C@H]([C@H]2[C@@H](O1)C[C@H]([C@@H](O2)[C@H]1[C@@H](C[C@]2([C@H](O1)[C@@H]([C@]1([C@H](O2)C[C@]2([C@H](O1)CC[C@]1([C@H](O2)C[C@]2([C@H](O1)C[C@H]1[C@H](O2)CC[C@H](O1)[C@]1([C@@H](C[C@H]2[C@](O1)(C[C@H]1[C@](O2)(CC[C@]2([C@H](O1)C[C@H]1[C@](O2)(C[C@H]2[C@H](O1)C/C=C\[C@H]1[C@H](O2)C[C@H]2[C@](O1)(C[C@]1([C@H](O2)C[C@H]2[C@](O1)(CC[C@H](O2)[C@H]([C@@H](C[C@@H](C)[C@@H](C)CC=C)O)O)C)C)C)C)C)C)C)O)C)C)C)C)C)O)C)O)O)O)O)O)O)O)O)O)O)O)O)O)OS(=O)(=O)[O-])O)O)O)O)C)C)O)O)O)O.[Na+].[Na+];
InChI	1/C164H258O68S2.2Na/c1-24-26-65(2)68(5)41-74(168)117(179)85-33-36-152(11)106(203-85)55-109-162(21,231-152)64-161(20)105(210-109)51-89-83(220-161)28-25-27-82-99(199-89)59-157(16)108(202-82)56-107-153(12,230-157)39-38-151(10)112(211-107)61-158(17)111(224-151)54-101(176)163(22,232-158)103-32-31-84-90(204-103)53-110-156(15,219-84)62-113-150(9,223-110)37-34-102-155(14,225-113)63-114-164(23,227-102)147(192)149-159(18,226-114)58-81(175)134(218-149)133-79(173)47-93-136(216-133)120(182)119(181)92(200-93)44-72(166)43-76(170)131-77(171)46-94-137(214-131)122(184)124(186)143(207-94)145-126(188)125(187)144-146(217-145)128(190)139-97(208-144)50-88-87(206-139)49-96-138(205-88)127(189)141(229-234(196,197)198)95(201-96)45-75(169)118(180)132-78(172)48-98-140(215-132)129(191)148-160(19,221-98)60-100-91(209-148)52-104-154(13,222-100)57-80(174)135-142(212-104)123(185)121(183)130(213-135)71(8)115(177)67(4)29-30-86(228-233(193,194)195)116(178)69(6)42-73(167)70(7)66(3)35-40-165;;/h24-25,28,35,65,67-69,71-149,165-192H,1,7,26-27,29-34,36-64H2,2-6,8-23H3,(H,193,194,195)(H,196,197,198);;/q;2*+1/p-2/b28-25-,66-35+;;/t65-,67+,68+,69+,71+,72+,73+,74+,75-,76+,77+,78+,79+,80+,81+,82+,83-,84+,85-,86-,87-,88+,89+,90-,91-,92-,93-,94-,95-,96+,97-,98+,99-,100+,101+,102+,103-,104+,105-,106-,107+,108-,109+,110+,111-,112-,113+,114+,115+,116+,117-,118+,119-,120+,121+,122+,123-,124+,125+,126+,127+,128+,129-,130-,131-,132-,133+,134+,135+,136+,137+,138+,139-,140+,141-,142-,143+,144-,145+,146+,147-,148+,149+,150-,151+,152+,153-,154-,155-,156-,157+,158+,159-,160-,161+,162-,163+,164+;;/m0../s1;
InChIKey	NWQUHAJRFNRIIU-NHOVDTRNBI
性質
化學式	C164H256O68S2Na2
摩爾質量	3425.85618 g/mol g·mol⁻¹
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

刺尾鯛毒素（英語：Maitotoxin，簡稱MTX）是一種由甲藻門中的崗比甲藻（Gambierdiscus toxicus）產生的劇毒物質。這種化合物是目前人類發現的毒性最強的非蛋白質類毒素：對小鼠的LD₅₀僅為50ng/kg，只需0.13µg/kg的腹膜注射便可致死。^[1] 刺尾鯛毒素常與西加魚毒素一同存在，並共同引起西加魚毒中毒。^[2] 刺尾鯛毒素最早被分離於一種能引起西加魚毒中毒的刺尾魚科魚類櫛齒刺尾鯛；這種魚在大溪地語被稱為「maito」，因此該毒素得名「maitotoxin」。後來人們則發現它實際上是由崗比甲藻產生的，經食物鏈蓄積於各種不同品種的魚類體內都有此毒素存在。^[3]

毒性作用機理

刺尾鯛毒素激活Ca²⁺通透性非選擇性陽離子通道（鈣通道），使得Ca²⁺內流，細胞內濃度急劇上升。通常認為刺尾魚毒素會在這些離子通道上形成孔道。這會產生一系列的生理作用（如細胞膜去極化），並最終激活細胞死亡級聯反應，導致質膜發泡並最後使細胞溶解。^[4] 刺尾魚毒素還激活細胞質基質中由鈣激活型蛋白酶鈣激活酶-1與鈣激活酶-2，從而導致細胞壞死。^[5] 此外，有研究顯示刺尾魚毒素也能引起許多與細胞內鈣離子濃度沒有直接關係的生物效應，因此它的毒性很有可能還有其他未知的作用機理。^[6]

分子結構

刺尾鯛毒素的分子為32個環組成的稠環結構，具有32個含氧雜環（環醚）、22個甲基、28個羥基和兩個硫酸酯基，其中硫酸酯基有着重要的生物學效應，對其毒性起到了決定性的作用。它是由生物產生的非蛋白，非多糖分子中最大的，最複雜的之一。^[7]^[8]^[9]^[10]

刺尾魚毒素的分子結構是由東北大學、哈佛大學和東京大學通過核磁共振及輔以質譜和化學合成確定的。然而，近年來Gallimore與Spencer等人在參照生物合成原理及水生生物聚醚的合成模型後認為目前的結構中的一個環形結（J-K環形結）有問題，因而懷疑整個結構的準確性。^[11] Nicolaou和Frederick則認為即使考慮到生物合成原理，目前的結構模型仍是正確的。^[12] 與此有關的爭議至今仍未解決。

生物合成

刺尾鯛毒素的生物合成的核心通過的是聚酮合酶路徑。^[11]

參考資料

^ Yokoyama, A; et al. Some Chemical Properties of Maitotoxin, a Putative Calcium Channel Agonist Isolated from a Marine Dinoflagellate. J. Biochem. 1988, 104 (2): 184–187. PMID 3182760.
^ YASUMOTO, T.; NAGAI, H.; YASUMURA, D.; MICHISHITA, T.; ENDO, A.; YOTSU, M.; KOTAKI, Y. Interspecies Distribution and Possible Origin of Tetrodotoxin. Annals of the New York Academy of Sciences (Wiley-Blackwell). 1986, 479 (1 Tetrodotoxin,): 44–51. ISSN 0077-8923. doi:10.1111/j.1749-6632.1986.tb15560.x.
^ Yasumoto, Takeshi. The chemistry and biological function of natural marine toxins. The Chemical Record (Wiley-Blackwell). 2001, 1 (3): 228–242. ISSN 1527-8999. doi:10.1002/tcr.1010.
^ Estacion, M and Schilling, WP. Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial cells. BMC Physiology. 2001, 1: 2. doi:10.1186/1472-6793-1-2.
^ Wang, K.; et al. Maitotoxin induces calpain activation in SH-SY5Y neuroblastoma cells and cerebrocortical cultures. Arch. Biochem. Biophys. 1996, 331 (2): 208–214. PMID 8660700. doi:10.1006/abbi.1996.0300.
^ M. Estacion, H. B. Nguyen, J. J. Gargus. Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells. The American Journal of Physiology. 1996-4, 270 (4 Pt 1): C1145–1152 [2019-02-13]. ISSN 0002-9513. PMID 8928742. doi:10.1152/ajpcell.1996.270.4.C1145. （原始內容存檔於2019-06-10）. 請檢查|date=中的日期值 (幫助)
^ Murata, M; et al. Structure and partial stereochemical assignments for maitotoxin, the most toxic and largest natural non-biopolymer. J. Am. Chem. Soc. 1994, 116 (16): 7098–7107. doi:10.1021/ja00095a013.
^ Sasaki, M; et al. The complete structure of maitotoxin, I; Configuration of the C1-C14 side chain. Angew. Chem. Int. Ed. Engl. 1996, 35 (15): 1672–1675. doi:10.1002/anie.199616721.
^ G. Sorrentino, M. R. Monsurrõ, I. N. Singh, J. N. Kanfer. Membrane depolarization in LA-N-1 cells. The effect of maitotoxin is Ca(2+)- and Na(+)-dependent. Molecular and Chemical Neuropathology. 1997-4, 30 (3): 199–211 [2019-02-13]. ISSN 1044-7393. PMID 9165486. （原始內容存檔於2019-06-09）. 請檢查|date=中的日期值 (幫助)
^ Kishi, Y. Complete structure of maitotoxin. Pure & Appl. Chem. 1998, 70 (2): 339–344. doi:10.1351/pac199870020339.
^ ^11.0 ^11.1 Gallimore AR, Spencer JB. Stereochemical Uniformity in Marine Polyether Ladders—Implications for the Biosynthesis and Structure of Maitotoxin. Angew. Chem. Int. Ed. Engl. 2006, 45 (27): 4406–4413. PMID 16767782. doi:10.1002/anie.200504284.
^ Nicolaou KC, Frederick MO. On the structure of maitotoxin. Angew. Chem. Int. Ed. Engl. 2007, 46 (28): 5278–82. PMID 17469088. doi:10.1002/anie.200604656.

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更多有聲條目

Jones, Maitland. Organic Chemistry, Third Edition. W. W. Norton & Company. 2004. ISBN 978-0-393-92408-4.

[1] Yokoyama, A; et al. Some Chemical Properties of Maitotoxin, a Putative Calcium Channel Agonist Isolated from a Marine Dinoflagellate. J. Biochem. 1988, 104 (2): 184–187. PMID 3182760.

[dyd-2] YASUMOTO, T.; NAGAI, H.; YASUMURA, D.; MICHISHITA, T.; ENDO, A.; YOTSU, M.; KOTAKI, Y. Interspecies Distribution and Possible Origin of Tetrodotoxin. Annals of the New York Academy of Sciences (Wiley-Blackwell). 1986, 479 (1 Tetrodotoxin,): 44–51. ISSN 0077-8923. doi:10.1111/j.1749-6632.1986.tb15560.x.

[Yasumoto_2001_pp._228–242-3] Yasumoto, Takeshi. The chemistry and biological function of natural marine toxins. The Chemical Record (Wiley-Blackwell). 2001, 1 (3): 228–242. ISSN 1527-8999. doi:10.1002/tcr.1010.

[4] Estacion, M and Schilling, WP. Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial cells. BMC Physiology. 2001, 1: 2. doi:10.1186/1472-6793-1-2.

[5] Wang, K.; et al. Maitotoxin induces calpain activation in SH-SY5Y neuroblastoma cells and cerebrocortical cultures. Arch. Biochem. Biophys. 1996, 331 (2): 208–214. PMID 8660700. doi:10.1006/abbi.1996.0300.

[6] M. Estacion, H. B. Nguyen, J. J. Gargus. Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells. The American Journal of Physiology. 1996-4, 270 (4 Pt 1): C1145–1152 [2019-02-13]. ISSN 0002-9513. PMID 8928742. doi:10.1152/ajpcell.1996.270.4.C1145. （原始內容存檔於2019-06-10）. 請檢查|date=中的日期值 (幫助)

[7] Murata, M; et al. Structure and partial stereochemical assignments for maitotoxin, the most toxic and largest natural non-biopolymer. J. Am. Chem. Soc. 1994, 116 (16): 7098–7107. doi:10.1021/ja00095a013.

[8] Sasaki, M; et al. The complete structure of maitotoxin, I; Configuration of the C1-C14 side chain. Angew. Chem. Int. Ed. Engl. 1996, 35 (15): 1672–1675. doi:10.1002/anie.199616721.

[9] G. Sorrentino, M. R. Monsurrõ, I. N. Singh, J. N. Kanfer. Membrane depolarization in LA-N-1 cells. The effect of maitotoxin is Ca(2+)- and Na(+)-dependent. Molecular and Chemical Neuropathology. 1997-4, 30 (3): 199–211 [2019-02-13]. ISSN 1044-7393. PMID 9165486. （原始內容存檔於2019-06-09）. 請檢查|date=中的日期值 (幫助)

[10] Kishi, Y. Complete structure of maitotoxin. Pure & Appl. Chem. 1998, 70 (2): 339–344. doi:10.1351/pac199870020339.

[poly-11] 11.0 ^11.1 Gallimore AR, Spencer JB. Stereochemical Uniformity in Marine Polyether Ladders—Implications for the Biosynthesis and Structure of Maitotoxin. Angew. Chem. Int. Ed. Engl. 2006, 45 (27): 4406–4413. PMID 16767782. doi:10.1002/anie.200504284.

[12] Nicolaou KC, Frederick MO. On the structure of maitotoxin. Angew. Chem. Int. Ed. Engl. 2007, 46 (28): 5278–82. PMID 17469088. doi:10.1002/anie.200604656.

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