Hepatotoxicity cyanobacterial

Fig. 5.1 Common cyanobacterial hepatotoxins. (a) Generalized structure of microcystin, a cyclic heptapeptide. Note that X and Z are L-amino acids. For example, microcystin-LR possesses lysine and arginine residues at X and Z, respectively, (b) Cylindrospermopsin, a hepatotoxic alkaloid from Cylindrospermopsis raceborskii...

Park, H.-D, Kim, B., Kim, E., and Okino, T. 1998. Hepatotoxic microcystins and neurotoxic anatoxin-a in cyanobacterial blooms from Korean lakes. Environ Toxicol Water Qual 13, 225-234. 

One of the invariant amino acids is a unique P-amino acid called Adda (2S,3S,8S,9S)-3 amino-9 methoxy-2,6,8-trimethyl-10-phei5fldeca-4,6-dienoic acid is the most unusual structure in this group of cyanobacterial cyclic peptide toxins). A two-letter suffix (XY) is ascribed to each individual toxin to denote the two variant amino acids (Carmichael 1988). X is commonly leucine, arginine, or tyrosine. Y is arginine, alanine, or methionine. Variants of all the invarianf amino acids have now been reported, e.g., desmethyl amino acids and/or replacement of the 9-methoxy group of Adda by an acetyl moiety. Currently there are in excess of 60 variants of microcystin that have been characterized (Rinehart 1994 Sivonen and Jones 1999). Of these 60 compounds, microcystin-LR would appear to be the microcystin most commonly found in cyanobacteria. It is also common for more than one microcystin to be found in a particular strain of cyanobacterium (Namikoshi 1992 Lawton 1995). The microcystin variants may also differ in toxicity (Carmichael 1993). The literature indicates that hepatotoxic blooms ofM aeruginosa containing microcystins occur commonly worldwide. 

The most important of the peptidic phosphatase inhibitors are the microcystins and nodularin. Mycrocystins are heptapeptides characterised by the sequence cyclo(D-Ala-X-D-e/>,r/iro-(3-methylisoAsp-Y-Adda-D-isoGlu-A-methyldehydroAla), where X and Y are different L-aminoacids, and Adda is the abbreviation of the (3-aminoacid [2 ,3S,8S,9S]-3-aniino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E),6(E)-dienoic acid. In the most common microcystin, namely microcystin-LR, X is Leu and Y is Arg. This kind of compounds was considered to be the highly hepatotoxic principle of the cyanobacterial genera Microcystis, Anabaena and Oscillatoria. Apart from the variations represented by X and Y, other differences arising from the demethylation of aminoacids, lead to the existence to more than fifty microcystins. The rare add Adda is also... 

There have been many biological methods developed for cyanotoxins that use the bioactivity of these toxins, such as potent hepatotoxicity, neurotoxicity, cytotoxicity, enzymatic activity, and immunological interactions. All these methods, although they are useful for sensitive screening of cyanotoxins, cannot detect and quantitate individual cyanobacterial toxins. Bioassays are recommended if any of these conditions are fulfilled [5] ... 

Namikoshi, M. Rinehart, K.L. Sakai, R. Sivonen, K. Carmichael, W.W. Stractures of three new cyclic hepato-toxins produced by the cyanobacterium (blue-green algae) Nostoc sp. strain 152. J. Org. Chem. 1990, 55, 6135-6141. Sivonen, K. Carmichael, W.W. Namikoshi, M. Rinehart, M.L. Dahlem, A.M. Niemela, S.I. Isolation and characterization of hepatotoxic microcystin homologues from the filamentous freshwater cyanobacterium Nostoc sp. strain 152. Appl. Environ. Microbiol. 1991, 56, 2650-2657. Sivonen, K. Jones, G. In Toxic Cyanobacteria in Water, Chorus, I., Bartram, J., Eds. E FN Spon London, 1999 41. BeU, S.G. Codd, G.A. Cyanobacterial toxins and human health. Rev. Med. Microbiol. 1994, 5, 256-264. 

Moroder, L. and Rudolph-Bohner, S. (1998) Microcystins and nodularins, hepatotoxic cyclic peptides of cyanobacterial origin, in Studies in Natural Product Chemistry (ed. Atta-Ur-Rahman), vol. 20, pp. 887-920. 

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