Microcystins and nodularins

These toxins are cyclic peptides with microcystins comprising seven amino acids while nodularins contain only five amino acids. A microcystin is depicted in the figure below. These toxins mediate their toxicity by inhibiting liver function. The amino acid composition of the individual microcystins or nodularins may vary the novel hydrophobic amino acid, 3-amino-9-methoxy-10-phenyl-2,6,8 trimethyl deca,4,6 dienoic acid (ADDA) is essential to its pharmacological activity. Like okadaic acid, which causes diarrhetic shellfish poisoning, microcystins and nodularins are potent inhibitors of the serine/threonine protein phosphatases, binding to the same site upon the enzymes as okadaic acid and may therefore act as tumour promoters.

Figure 6 Microcystis

Where these toxins are found

In freshwater, the blue green algae, Anabaena, Nodularia, Nostoc, Oscillatoria and Microcystis from which the microcystins derive their name. Over fifty microcystin analogues are known. Nodularin is found in the blue-green alga Nodulara spumigena which usually occurs in brackish waters such as that found in estuaries. There have been reports of microcystins in the marine shellfish, namely the blue mussel Mytilus edulis, although the source of the toxin was not identified. Of more prominent concern is the potential for these toxins to contaminate drinking water, a situation that may impact not only humans but also agricultural livestock and wildlife. It has been claimed by some that toxins from cyanobacteria contaminated water in a kidney dialysis clinic in Brazil and contributed to human deaths. Salmon, striped bass and shrimp have been found to harbour microcystins, with the fish usually dying from acute liver failure, the so-called net pen liver disease, while the toxins may be accumulated in the shrimp's tissues.

As mentioned above, these toxins inhibit serine/threonine protein phosphatases enzymes responsible for removing phosphate groups from other proteins, the process of dephosphorylation, which acts as a switch for the activity of the target of these phosphatases. The liver is particularly susceptible to these toxins because unlike many other cell types, these peptides are able to penetrate the liver cells and are specifically taken up through the bile acid transport pathway. These toxins damage the liver by affecting the maintenance by these phosphatases of the cytoskeleton, which is comprised of a network of protein filaments. In a healthy cell, although these protein filaments shrink, grow, and dissociate and associate on an ongoing basis, the general size of the cytoskeleton stays constant. Microcystins and nodularins cause the cytoskeleton to collapse then because the balance of phosphate groups on the cytoskeletal proteins is disrupted, and the liver cells implode. The liver cells, along with the capillary cells, pull apart releasing blood into the liver. Blood pooling occurs in the liver, and death results.

Of a more long term concern is that microcystins and nodularins are liver tumour promoters in test animals. Epidemiology suggests that there may be a positive correlation between levels of microcystin in fresh water supplies in certain areas of China and the number of human liver cancer cases.

Carmichael WW (1994) The toxins of cyanobacteria. Sci Am 270, 78-86.

Chen DZX, Boland MP, Smillie MA, Klix H, Ptak C, Andersen RJ & Holmes CF (1993) Identification of protein phosphatase inhibitors of the microcystin class in the marine environment. Toxicon 31, 1407-1414.

Jochimson EM, Carmichael WW, An JS, Cardo DM, Cookson ST, Holmes CEM, Autines MBD, Demelo DA, Lyra TM, Barreto VST, Azevedo SMFO & Jarvis WR(1998) Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. NE. J Med 338, 873-878.

MacKintosh C, Beattie KA, Klumpp S, Cohen P & Codd GA (1990) Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett 264, 187-1920.

Nishiwaki-Matsushima R, Nishiwaki S, Ohta T, Yoshizawa S, Suganuma M, Harada K, Watanabe MF & Fujiki H (1991) Structure-function relationships of microcystins, liver tumor promoters, in interaction with protein phosphatase. Jpn J Cancer Res 82, 993-996.

Williams DE, Dawe SC, Kent ML, Andersen RJ, Craig M & Holmes CFB (1997) Bioaccumulation and clearance of microcystins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues. Toxicon 35:1617-1625.

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Page last updated - December 18, 2008

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