Pumiliotoxin
Pumiliotoxin B: R = –OH
Pumiliotoxins (PTXs), are one of several toxins found in the skin of poison dart frogs. The frog species, P. bibronii also produces PTXs to deter predators. Closely related, though more toxic, are allopumiliotoxins, (aPTXs). Other toxins found in the skin of poison frogs include decahydroquinolines (DHQs), izidines, coccinellines, and spiropyrrolizidine alkaloids. Pumiliotoxins are poisonous in high concentrations. Pumiliotoxins are much weaker than batrachotoxins, ranging between 100 and 1000 times less poisonous.
Structure
[edit]The different divisions of compounds in the pumiliotoxin-A class arise from differences in the carbon backbone and/or the substituents attached to it. The difference between allopumiliotoxins and pumiliotoxins occurs at the 7 position. At this position, pumiliotoxins have a hydrogen whereas allopumiliotoxins have a hydroxyl substituent. Both have methyl and hydroxyl groups at the C-8 position. Homopumiliotoxins contain a quinolizidine ring in the place of the indolizidine ring and methyl and hydroxyl groups at its C-9 position. All three contain an alkylidenyl side-chain.[1]
Nomenclature
[edit]Pumiliotoxins (or their analogs, allopumiliotoxins and homopumiliotoxins) are named by their class followed by their molecular weight. Isomers are differentiated by a letter after the number. For example, allopumiliotoxin 339A is an allopumiliotoxin with a molecular weight of 339 g/mol, with an axially oriented hydroxyl group at the 7-position in the indolizidine nucleus that differentiates it from allopumiliotoxin 339B.[2] A (+) or (−) sign preceding the name of a pumiliotoxin refers to the compound’s rotation of polarized light, with clockwise rotation (dextrorotatation) denoted with (+) and counterclockwise rotation (levorotation) denoted with (-). [3]
Accumulation
[edit]Frogs obtain pumiliotoxins from their diet in arthropods;[4][5] frogs raised in terrariums in the absence of their natural diet do not produce alkaloids.[6] The toxins are then accumulated in secretory granular glands of the skin of the frog.[7] Some frog species of the Dendrobates genera can convert pumiliotoxins into allopumiliotoxins[8] by a hydroxylase.[9] Only one of the enantiomers can be hydroxylated to this more potent form of the toxin.
The lack of pumiliotoxin 251D in eggs and tadpoles show that the toxin is not passed over from adult frogs to their offspring.[10] The tadpoles are therefore not readily protected from predators.
Physiological Effects
[edit]Pumiliotoxins and allopumiliotoxins are generally positive modulators of voltage gated sodium channels and increase the strength of heart contraction.[11] One exception is pumiliotoxin 251D, which blocks the flux of Na+ ions and increases the permeability of K+ ions.[12]
See also
[edit]References
[edit]- ^ Jain, P.; Garraffo, H. M.; Spande, T. F.; Yeh, H. J. C.; Daly, J. W. J. Nat. Prod. 1995, 58, 100-104.
- ^ Aoyagi, S.; Wang, T. C.; Kibayashi, C. J. Am. Chem. Soc. 1993, 115, 11393-11409.
- ^ Bruice, P. Y. Organic Chemistry; Pearson Prentice Hall: Upper Saddle River, NJ, 2007; pp 212-213.
- ^ Saporito RA, Garraffo HM, Donnelly MA, Edwards AL, Longino JT, Daly JW (May 2004). "Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs". Proceedings of the National Academy of Sciences of the United States of America. 101 (21): 8045–50. doi:10.1073/pnas.0402365101. PMC 419554. PMID 15128938.
- ^ Takada W, Sakata T, Shimano S, Enami Y, Mori N, Nishida R, Kuwahara Y (October 2005). "Scheloribatid mites as the source of pumiliotoxins in dendrobatid frogs". Journal of Chemical Ecology. 31 (10): 2403–15. doi:10.1007/s10886-005-7109-9. PMID 16195851. S2CID 535250.
- ^ Daly JW, Secunda SI, Garraffo HM, Spande TF, Wisnieski A, Nishihara C, Cover JF (August 1992). "Variability in alkaloid profiles in neotropical poison frogs (Dendrobatidae): genetic versus environmental determinants". Toxicon. 30 (8): 887–898. Bibcode:1992Txcn...30..887D. doi:10.1016/0041-0101(92)90387-k. PMID 1523680.
- ^ Daly JW, Garraffo HM, Spande TF, Clark VC, Ma J, Ziffer H, Cover JF (September 2003). "Evidence for an enantioselective pumiliotoxin 7-hydroxylase in dendrobatid poison frogs of the genus Dendrobates". Proceedings of the National Academy of Sciences of the United States of America. 100 (19): 11092–7. Bibcode:2003PNAS..10011092D. doi:10.1073/pnas.1834430100. PMC 196932. PMID 12960405.
- ^ "Toxins". World of Frogs. Retrieved 8 March 2016.
- ^ Alvarez-Bullya A, Payne C, Vidoudez C, Trauger S, O'Connell L (March 2022). "Molecular physiology of pumiliotoxin sequestration in a poison frog". PLOS ONE. 17 (3): e0264540. Bibcode:2022PLoSO..1764540A. doi:10.1371/journal.pone.0264540. PMC 8916643. PMID 35275922.
- ^ "Poison Dart Frog – The Deadliest Frog on Earth". FactsList.net. 10 February 2013. Retrieved 8 March 2016.
- ^ Daly JW, McNeal E, Gusovsky F, Ito F, Overman LE (February 1988). "Pumiliotoxin alkaloids: relationship of cardiotonic activity to sodium channel activity and phosphatidylinositol turnover". Journal of Medicinal Chemistry. 31 (2): 477–480. doi:10.1021/jm00397a036. PMID 2448459.
- ^ Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, et al. (March 2008). "Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians". Toxicon. 51 (3): 334–44. doi:10.1016/j.toxicon.2007.10.011. PMID 18061227.
External links
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