2 October 2017

Anatoxin-A - a neurotoxic amine

Natural toxin

Anatoxin A (ATX-A) is a semi-rigid bicyclic secondary amine molecule that presents acute neurotoxic activity. It is naturally produced by at least five genus of freshwater cyanobacteria

Name: Anatoxin-a

Figure 1. Structure of ATX-A. Click image for interactive 3D structure

CAS #:64285-06-9

Formula: C10H15NO                                                  

Molecular weight: 166.24 g/mol                                                   

IUPAC name: 1-(9-azabicyclo(4.2.1)non-2-en-2-yl)-ethanone

Anatoxin A (ATX-A) is a semi-rigid bicyclic secondary amine molecule that presents acute neurotoxic activity. The enantiomer (+)-anatoxin-a is naturally produced by at least five genus of freshwater cyanobacteria, including several strains of Anabaena  (i.e. Anabaena circinalis, Anabaena flos-aquae NRC 44-1 and Anabaena flos-aquae NRC 525-17), Aphanizomenon, Microcystis, Planktothrix and Oscillatoria.

As a toxin, ATX-A is a nicotinic agonist that binds irreversibly to nicotinic acetylcholine receptors (nAChRs) in neurons and neuromuscular junctions. Its interaction with nAChRs causes the opening of the Na+/Ca2+ channels and, ultimately, causes its blockage, resulting in muscular malfunction. In acute toxicity tests, the administration of (+)-anatoxin-a has been observed to cause loss of coordination (altered gait and tremors), hyperactivity, muscular twitching and death by respiratory paralysis (LD=13.3 mg kg-1 in male Swiss Webster ND-4 mice).

Cases of human injury through cyanotoxins are well documented. The most common route of exposure is drinking water, causing - in some cases serious - illness through ingestion or aspiration of toxic cyanobacteria.

In the aquatic system, ATX-A is expected to largely remain in solution (solubility 7.2·104 mg/l), without being significantly adsorbed to particulate material or sediment (estimated KOC=76). Its bioaccumulation potential is also suggested to be low (BCF=2.6, estimated from a log KOW of 1.1).  ATX degrades in water, particularly at high pH waters (ATX-A  was found to be stable for 21 days at pH 4, but less than 5 % remained at pH 8-10 after 2 weeks) and in presence of sunlight irradiation. The degradation of ATX-A produces several non-toxic compounds, including the hydrogenated form, dihydroanatoxin-A, and anatoxin-A epoxide, both of which have been detected in the real environment. Volatilization from water surfaces is not favoured, based upon an estimated Henry's Law constant of 6.6·10-9 atm m3 mol-1 (SRC). In air, ATX-A remains in the vapour phase and is readily degraded by hydroxyl radicals (half-life, 1.1 h)

Further reading:

Kuiper-Goodman T et al; Chapter 4 Human Health Effects. In: Toxic Cyanobacteria in Water: A guide to their public health consequences, monitoring and management. ISBN 0-419-23930-8. WHO (1999)

Fawell, J.K., R.E. Mitchell, R.E. Hill and D.J. Everett. 1999. The toxicity of cyanobacterial toxins in the mouse: II Anatoxin-a. Hum. Exp. Toxicol. 18(3):168-173.

James, Kevin J., et al. "Sensitive determination of anatoxin-a, homoanatoxin-a and their degradation products by liquid chromatography with fluorimetric detection." Journal of Chromatography A 798.1 (1998): 147-157.

Kaminski, Ariel, et al. "Determination of anatoxin-a stability under certain abiotic factors." Harmful Algae 28 (2013): 83-87.

James HA, Smith C, Sutton A Persistence of anatoxin-A in reservoir water. Foundation for Water Research Report No. FR0427 (1993).

Puschner, Birgit, and Caroline Moore. "Cyanobacteria." Small Animal Toxicology, Third Edition. Elsevier Inc., 2012.

Sanchez, Jon A., et al. "Detection of anatoxin-a and three analogs in Anabaena spp. cultures: New fluorescence polarization assay and toxin profile by LC-MS/MS." Toxins 6.2 (2014): 402-415.

Stevens, D.K. and R.I. Krieger. 1991. Effect of route of exposure and repeated doses on the acute toxicity in mice of the cyanobacterial nicotinic alkaloid anatoxin-a. Toxicon. 29(1):134-138

Viaggiu, E., S. Melchiorre, F. Volpi et al. 2004. Anatoxin-a toxin in the cyanobacterium Planktothrix rubescens from a fishing pond in northern Italy. Environ. Toxicol. 19(3):191-197.

Photos:

  1. Anabaena circinalis By Bdcarl - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19074360.
  2. Oscillatoria. Photo: Otago Regional Council & Landcare Research.
  3. Planktothrix rubescens. By Kristian Peters http://www.korseby.net/outer/flora/algae/index.html - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9432593