1912:
887:. This part of the synthesis is catalyzed by enzyme domains that possess β-ketoacylsynthase, acyltransferase, C-methyltransferase and ketoacyl reductase activity. At the end of this stage, that is, after the first condensation of glutamate, the amino acid Adda is formed. The second part of the synthesis involves the condensation of the amino acids of which the microcystin is composed. Thus, in the case of microcystin-LR the consecutive condensation of the amino acids glutamic acid, methyldehydroalanine, alanine, leucine, methylaspartic acid and arginine leads to the coupled product. A nucleophilic attack of the nitrogen in the Adda residue results in the release of the cyclic microcystin-LR.
1731:
377:
242:
787:
868:
45:
601:
2192:
410:
InChI=1S/C49H74N10O12/c1-26(2)23-37-46(66)58-40(48(69)70)30(6)42(62)55-35(17-14-22-52-49(50)51)45(65)54-34(19-18-27(3)24-28(4)38(71-10)25-33-15-12-11-13-16-33)29(5)41(61)56-36(47(67)68)20-21-39(60)59(9)32(8)44(64)53-31(7)43(63)57-37/h11-13,15-16,18-19,24,26,28-31,34-38,40H,8,14,17,20-23,25H2,1-7,9-10H3,(H,53,64)(H,54,65)(H,55,62)(H,56,61)(H,57,63)(H,58,66)(H,67,68)(H,69,70)(H4,50,51,52)/b19-18+,27-24+/t28-,29-,30-,31+,34-,35-,36+,37-,38-,40+/m0/s1
400:
InChI=1S/C49H74N10O12/c1-26(2)23-37-46(66)58-40(48(69)70)30(6)42(62)55-35(17-14-22-52-49(50)51)45(65)54-34(19-18-27(3)24-28(4)38(71-10)25-33-15-12-11-13-16-33)29(5)41(61)56-36(47(67)68)20-21-39(60)59(9)32(8)44(64)53-31(7)43(63)57-37/h11-13,15-16,18-19,24,26,28-31,34-38,40H,8,14,17,20-23,25H2,1-7,9-10H3,(H,53,64)(H,54,65)(H,55,62)(H,56,61)(H,57,63)(H,58,66)(H,67,68)(H,69,70)(H4,50,51,52)/b19-18+,27-24+/t28-,29-,30-,31+,34-,35-,36+,37+,38-,40+/m0/s1
1994:
1340:. The WHO report states that microcystins are lethal to mice when they are exposed intraperitoneally to 25 to 150 μg/kg body weight. Perhaps due to poor absorption after exposure, orally administered microscytins are less toxic, as a lethal dose in mice is about 5 to 10 μg/kg body weight. Hepatotoxicity in the form of hepatic necrosis occurs within 60 minutes after an intraveneous dose. Blooms of
1374:
response to DNA damage after a 4-hour exposure. After 24 hours, the DNA damage-responsive genes were upregulated, which indicates that microcystin-LR is an indirect genotoxic agent. In China, the highest incidence of liver cancer occurs in areas with abundant cyanobacteria in the surface waters. Tumor development is associated with low-concentration exposure over a long period of time.
926:
carboxylic D-Glu site makes hydrogen bonds to metal-bound water molecules and the carboxyl group of the Masp site makes hydrogen bonds to conserved arginine and tyrosine residues in the PPP enzyme. Finally the methylene group at the Mdha site of microcystin-LR binds covalently to a S-atom of a cysteine residue, and the leucine residue packs closely to another conserved tyrosine residue.
693:
151:
910:) activities in the cytoplasm of liver cells. This leads to an increase in phosphorylation of proteins in liver cells. The interaction of microcystin-LR to the phosphatases includes the formation of a covalent bond between a methylene group of microcystin-LR and a cystine residue at the catalytic subunit of the
1087:
Data about the metabolism of microcystin-LR in humans is very scarce. Data about metabolism and disposition of the toxin in mice and rats is more widely available. In these animals microcystin-LR is rapidly concentrated in the liver. Intoxication of mice with microcystin-LR led to a decrease in the
1184:
For the assessment of possible chronic human health effects, studies involving repeated oral administration of pure microcystins at various dose levels are most desirable. In a mice study, pure mirocystin-LR was administered orally at doses 0, 40, 200 or 1000 μg/kg bodyweight. At the highest dose,
1037:
Cyanobacteria prefer to live in water bodies such as lake, ponds, reservoirs, and slow-moving streams. When the water is warm there are enough nutrients available for the bacteria to survive. Most cyanobacteria produce toxins, of which microcystin is only one group. When a cyanobacterium dies, its
1935:
Oberholster, P.J., Cloete, T.E., van Ginkel, C., Botha, A-M. & Ashton, P.J. 2008. The use of remote sensing and molecular markers as early warning indicators of the development of cyanobacterial hyperscum crust and microcystin-producing genotypes in the hypertrophic Lake
Hartebeespoort, South
1458:
from a river in southern China. The first published report of an incidence of cyanobacteria poisoning dates from the poisoning of an
Australian lake in 1878. Also, in China and Brasil, people died after drinking water from a lake. All these incidents have been attributed to cyanobacteria and the
1071:
Microcystin-LR is rapidly excreted from the blood plasma. Plasma half-lives for the α- and β-stages, corresponding to distribution and elimination, are respectively 0.8 and 6.9 minutes. The total clearance of the compound from the plasma is about 0.9 mL/min. The excretion of the compound takes
1100:
In phase 2 of the biotransformation the compound is conjugated with several different endogenous substances. Microcystin-LR is known to be excreted as glutathione conjugate, cysteine conjugate and an oxidized ADDA diene conjugate. The glutathione and cysteine conjugate with the Mda-moiety. The
925:
The active site of catalytic PPP enzymes represents three surface grooves: the hydrophobic groove, the acidic groove and the C-terminal groove, which are Y-shaped with the active site at the bifurcation point. The Adda side-chain of microcystin-LR is accommodated to the hydrophobic groove, the
1373:
The WHO states microcystin-LR has no mutagenic effect. However, the induction of DNA strand-breaks in lymphocytes has been observed in mice after single oral administration. The effect is time- and dose-dependent. There is no change in the expression of selected genes involved in the cellular
951:
There are no verifiable reports of human deaths known to have been specifically caused by microcystin-LR, although there are reports of health effects after exposure and there have been deaths attributed to microcystins in general. One of the most outstanding reports was an outbreak in
1219:
The IARC committee concluded that microcystin-LR is possibly carcinogenic to humans. So, microcystin-LR itself is not a carcinogen, but it stimulates tumor growth. Mice treated with the carcinogenic compound dimethylbenzathracene showed an increased number and weight of skin tumors.
849:, coined 'modules', that each have their own specific enzymatic function. Although the enzyme systems involved in the biosynthesis of microcystins is not identical among all cyanobacteria, there are large similarities and most of the essential enzymes are conserved.
1096:
and an increase in cytochrome P420, to which CYP450 is converted. Together with the fact that mice with an induced higher concentration CYP450 are less affected by the toxin, this suggest that CYP450 plays an important role in the detoxification of the compound.
1004:
Acute microcystin-LR intoxication may result in long-term injury, while chronic low-level exposure may cause adverse health effects. From animal studies, it is proven that there will be chronic liver injury from oral exposure to microcystin-LR. It might even be
938:
Microcystin-LR is toxic for both humans and animals. There are epidemiological results from studies that have shown symptoms of poisoning attributed to the presence of cyanotoxins in drinking water. The effects are divided in short-term and long-term effects.
1021:
Microcystin-LR had effects on all animals, not only the domestic animals from swimming in a river of drinking water with cyanobacteria blooms. Symptoms in domestic animal poisoning include diarrhea, vomiting, weakness, recumbency and are fatal in most cases
960:, in 1996. 116 patients experienced multiple effects: visual disturbance, nausea, vomiting and muscle weakness. One hundred developed acute liver failure and 52 suffered from symptoms of what is now called "Caruaru Syndrome." The syndrome was caused by
794:
More than 250 microcystins have been identified to date, representing differences in the two variable residues and some modifications in the other amino acids. These modifications include demethylation of Masp and Mdha and methylesterification of
980:
compounds; therefore, noticeable toxic effects are not immediate. Most of the toxicity studies have been done with mice that received intra-peritoneal injections. The most common effect is liver damage, Two of the most commonly seen symptoms are
609:
581:
1206:
Mice showed neoplastic liver nodules after 100 oral administrations at 20 μg/kg bodyweight. The nodules observed were up to 5mm in diameter. However, no mice showed liver nodules after 100 administrations of 80 μg/kg.
1171:
of both the olfactory and respiratory zones were suffering from necrosis. Even liver lesions were noticed after oral administration. The LD50 for nasal administration is equal to the intraperitoneal administration.
1348:
of the liver. There results are, however, ambiguous. By the oral route, microcystin-LR displays acute toxicity in rodents. It is apparent that a significant amount of the oral dose passes the intestinal barrier.
1042:
of this toxin is 3 weeks at pH 1 and 40 °C. At typical conditions in the environment, however, the half-life is 10 weeks. Microcystin-LR water contamination is resistant to boiling and microwave treatments.
992:
In an experiment with mice, the animals died within a few hours after injection of a lethal dose of micocystin-LR. Liver damage could be noticed in 20 minutes. Within a few hours, liver cells died.
771:-β-Me-isoAsp). Furthermore, microcystins contain two variable residues, which make the differentiation between variants of microcystins. These two variable functionalities are always standard
1153:. Because of the differences in lipophilicity and polarity between the different microcystins, it cannot be presumed that the i.p. LD50 will predict toxicity after oral administration.
1344:
did not cause increased tumor rates in groups of mice treated for up to one year. It is shown that mice given 20 μg/kg body weight 4 times a week during a period of 28 weeks developed
1976:
Matthews, M.W., & Barnard, S. 2015. Eutrophication and
Cyanobacteria in South Africa's Standing Water Bodies: A View from Space. In South African Journal of Science. Vol. 111. No. 5/6.
1949:
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primarily place via the feces and urine. After 6 days approximately 24% of the intake is excreted from the body, of which about 9% is excreted via the feces and 14.5% via the urine.
860:
enzyme. In a series of reactions, catalysed by different enzyme modules as well as different enzymes, microcystin-LR is formed. The entire biosynthesis pathway of microcystin-LR in
1156:
Microcystins are hepatotoxins. After acute exposure, severe liver damage is noticeable by a disruption of liver cell structure. The liver weight will increase due to intrahepatic
1038:
cell wall degrades while the toxins are released in the water. Microcystins are extremely stable in water and withstand chemical breakdown such as hydrolysis or oxidation. The
1463:(WHO) issued a guideline for microcystins in drinking water. The WHO guideline for microcystins in drinking water, based on microcystin-LR, is 1 μg/L. With the high levels of
706:
1185:
almost all mice showed liver changes and chronic inflammation and a few other symptoms. In female mice only changes in transaminases were observed at the highest dose.
1503:
Computational study of the covalent bonding of microcystins to cysteine residues - a reaction involved in the inhibition of the PPP family of protein phosphatases
914:(PPP) family of serine/threonine-specific phosphatases, like PP1 and PP2A. When microcystin-LR binds directly to the catalytic center of the PPP enzymes, they
918:
the access of the substrate to the active site completely and inhibition of the enzyme takes place. In this way the protein phosphatase is inhibited and more
423:
93:)-15--18--1,5,12,19-tetramethyl-2-methylidene-8-(2-methylpropyl)-3,6,9,13,16,20,25-heptaoxo-1,4,7,10,14,17,21-heptazacyclopentacosane-11,22-dicarboxylic acid
1025:
Mircocystin-LR is toxic for all animals, including the animals consumed by humans. Fishes and birds are also at risk for microcystin-LR poisoning.
1454:
The
Chinese general Zhu-Ge Liang was the first to observe cyanobacteria poisoning about 1000 years ago. He reported the death of troops who drank
1137:. Microcystins are generally associated with hepatotoxicity. The toxic effect of microcystins is due to their inhibition of protein phosphatases.
1009:. Cancers have been found during animal studies. Microcystin-LR itself does not cause cancer, but it may stimulate the growth of cancer cells.
2028:
1946:
1636:
Cyanobacterial toxins: Microcystin-LR in drinking-water. Background document for preparation of WHO Guidelines for drinking-water quality
1536:
Structural organization of microcystin biosynthesis in
Microcystis aeruginosa PCC7806: an integrated peptide-polyketide synthetase system
431:
CC1C(NC(=O)C(NC(=O)C(C(NC(=O)C(NC(=O)C(NC(=O)C(=C)N(C(=O)CCC(NC1=O)C(=O)O)C)C)CC(C)C)C(=O)O)C)CCCN=C(N)N)C=CC(=CC(C)C(CC2=CC=CC=C2)OC)C
1562:
Polyketide
Synthase Gene Coupled to the Peptide Synthetase Module Involved in the Biosynthesis of the Cyclic Heptapeptide Microcystin
391:
2236:
1235:
There is very little known about acute toxicity for humans, but there have been animal studies, showing the following results.
562:
278:
1046:
After release in the water, microcystins are actively absorbed by fish and birds from intoxicated water and thus enter the
2241:
334:
355:
1945:
Turton, A.R. 2015. Water
Pollution and South Africa's Poor. Johannesburg: South African Institute of Race Relations.
1801:
Kondo, F., Matsumoto, H., Yamada, S., Ishikawa, N., Ito, E., Nagata, S., Ueno, Y., Suzuki, M. and Harada, K.-I. 1996
1578:
Microcystins: A brief overview of their toxicity and effects, with special reference to fish, wildlife and livestock.
1828:
2068:
911:
713:
2021:
1998:
1964:
Turton, A.R. 2016. South Africa and the
Drought that Exposed a Young Democracy. In Water Policy (18); 210 – 227.
1872:"Degradation of [Dha7]MC-LR by a Microcystin Degrading Bacterium Isolated from Lake Rotoiti, New Zealand"
1460:
1333:
1150:
986:
761:
249:
2216:
799:-Glu. Different microcystins have different toxicity profiles, with microcystin-LR found to be the most toxic.
772:
543:
756:. The seven amino acids that are involved in the structure of a microcystin include the unique amino acids
237:
2221:
1947:
http://irr.org.za/reports-and-publications/occasional-reports/files/water-pollution-and-south-africas-poor
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Somdee, Theerasak; Thunders, Michelle; Ruck, John; Lys, Isabelle; Allison, Margaret; Page, Rachel (2013).
817:
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The first steps of the synthesis involve the insertion of several carbon- and oxygen atoms between the
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2195:
2014:
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Distribution of
Microcystis aeruginosa peptide toxin and interactions with hepatic microsomes in mice
1759:
Toxic cyanobacteria in water; A guide to their public health consequences, monitoring and management.
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922:
proteins in the liver cells are left, which is responsible for the hepatotoxicity of microcystin-LR.
812:
1965:
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Clinical and pathologic findings of blue-green algae (Microcystis aeruginosa) intoxication in a dog.
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Microcystin-LR is mostly concentrated in the liver. Other tissues get exposed at much lower levels.
2162:
1329:
826:
372:
117:
976:
There are few short-term effects caused by exposure to microcystin-LR. Microcystins are primarily
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Health hazards for terrestrial vertebrates from toxic cyanobacteria in surface water ecosystems.
1442:. This particular enzyme turns microcystins into products with a 160-fold decrease in toxicity.
1903:
1722:
1102:
757:
219:
1893:
1883:
1712:
1405:
1401:
915:
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microcystin-LR is synthesized by proteins that encoded by a 55 kb microcystin-gene cluster (
446:
127:
1701:"Microwave oven and boiling waterbath extraction of hepatotoxins from cyanobacterial cells"
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2177:
1953:
1841:
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Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil
1050:. Humans are also exposed to microcystins by performing activities in intoxicated water.
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Tissue distribution, excretion and hepatic biotransformation of microcystin-LR in mice
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The different microcystins are all synthesized by the same enzymes as microcystin-LR.
2210:
2152:
2147:
1700:
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Human intoxication by microcystins during renal dialysis treatment in
Caruaru-Brazil.
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2007:
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https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/microcystin_508.pdf
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Stability of microcystins from cyanobacteria. III. Effect of pH and temperature
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Robinson, N.A., Pace, J.G., Matson, C.F., Miura, G.A. and Lawrence, W.B. 1991
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Microcystin Biosynthesis in Planktothrix: Genes, Evolution, and Manipulation
1415:
1345:
44:
1907:
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649:
1993:
1888:
867:
1408:. Mutagenicity does not appear to occur for purified toxins derived from
1336:, they localize in the liver. This appears to be the result of uptake by
1157:
780:
24:
1936:
Africa. Pretoria: Council for Scientific and Industrial Research (CSIR).
645:
953:
790:
The chemical composition of microcystin-LR, id made up of 7 amino acids
776:
753:
503:
310:
250:
1649:
Atypical pulmonary thrombosis caused by a toxic cyanobacterial peptide
1855:
Microcystin-LR induced DNA damage in human periphal blood lymphocytes
1487:
Structural Diversity, Characterization and Toxicology of Microcystins
957:
884:
880:
633:
190:
825:) that contains 6 large (over 3 kb) genes that encode proteins with
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Except where otherwise noted, data are given for materials in their
1803:
Detection and identification of metabolites of microcystins formed
298:
170:
150:
140:
1966:
http://wp.iwaponline.com/content/ppiwawaterpol/18/S2/210.full.pdf
637:
1397:
1258:
902:
Microcystin-LR inhibits protein phosphatase type 1 and type 2A (
866:
289:
2006:
1467:
in South Africa, typical exposures can be as high as 10 μg/L.
629:
1516:
Molecular Mechanisms of Microcystin Toxicity in Animal Cells
1392:
studies showed that microcystin-LR is a potent inhibitor of
360:
1361:
Microcystins do not appear to show developmental toxicity.
2010:
1638:. Geneva, World Health Organization WHO/SDE/WSH/03.04/57).
1459:
toxic compound microcystin-LR. That is the reason why the
1827:
National Toxicology Program Microcystin Toxicity report,
1580:
Department of Water Resources, California. January 2009.
1842:
http://www.sigmaaldrich.com/catalog/product/sigma/m2912
964:
therapy with water that had not been properly treated.
701:
1668:
Journal of Veterinary Diagnostic Investigation, 1993.
486:
1505:, FEBS Journal, doi: 10.1111/j.1742-4658.2011.08454.x
277:
1163:After nasal administration of microcystin-LR, the
829:activity, nonribosomal peptide synthase activity (
856:begins with the coupling of phenylacetate to the
845:). These large proteins are made up of different
322:
1160:, haemodynamic shock, heart failure and death.
126:
2120:
2087:
2044:
1823:
1821:
1819:
1817:
1815:
2022:
1699:Metcalf, James S.; Codd, Geoffrey A. (2000).
1501:S. Pereira, V. Vasconcelos & A. Antunes,
428:
396:
1779:, J.Pharmacol. Exp. Ther., 256(1), 176-182.
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2015:
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1518:, Int. J. Mol. Sc., 11(1), pp. 268-287
871:The biosynthesis of microcystin-LR by
852:The biosynthesis of microcystin-LR in
231:
1809:Chem. Res. Toxicol., 9(8), 1355-1359.
403:Key: ZYZCGGRZINLQBL-JCGNTXOTSA-N
198:
178:
27:From Wikipedia, the free encyclopedia
1792:Pharmacol. Toxicol., 60(3), 187-191.
1551:, J. Bacteriol., 185(2), pp. 564-572
1237:
1840:Sigma Aldrich product information,
1438:, among other locations, is called
1101:oxidized ADDA is conjugated at the
313:
297:
2208:
1718:10.1111/j.1574-6968.2000.tb09021.x
35:
1788:Brooks, W.P. and Codd, G.A. 1987
1745:Phycologia, 1996. 35(6) pp. 83-88
1564:, J. Biochem., 127(5), pp.779-789
1538:, Chem. Biol., 7(10), pp. 753-764
1434:enzyme isolated from bacteria at
2191:
2190:
1992:
1514:A. Campos & V. Vasconcelos,
1479:
691:
599:
464:
458:
43:
1857:. Mutation Research 725(2011).
1328:When microcystins are injected
687:(at 25 °C , 100 kPa).
19:
1151:intraperitoneal administration
864:is illustrated in the figure.
775:- In microcystin-LR these are
736:. It is the most toxic of the
563:Occupational safety and health
470:
452:
1:
1761:London: E & FN Spon,1999.
1489:, doi: 10.3390/toxins11120714
1149:Many studies took place with
1121:are very diverse and include
1757:Chorus, I., and J. Bartram,
1176:Repeated oral administration
1576:Bulter, N., Carlisle, J.C.
1414:, although the toxins were
1406:cyclic AMP-dependent kinase
659:or concentration (LD, LC):
2258:
1844:(accessed on 1 March 2012)
1241:Method of administration
1054:Disposition and metabolism
912:phosphoprotein phosphatase
2186:
1924:Poisonous Australian lake
1705:FEMS Microbiology Letters
1461:World Health Organization
987:cholestatic liver disease
773:proteinogenic amino acids
732:) is a toxin produced by
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1606:Jochimsen, E.M. et al.,
1547:G. Christiansen et al.,
752:Microcystins are cyclic
105:-Arginine-microcystin LA
1926:Nature 18, 11-12 (1878)
1831:(accessed 1 March 2012)
1807:in mouse and rat livers
1664:DeVries, S.E., et al.,
1647:Slatkin, D.N., et al.,
1418:for human lymphocytes.
1400:, but has no effect on
1211:Interaction with tumors
1141:Acute subacute toxicity
837:) and 4 smaller genes (
811:Microcystins are small
2237:Phosphatase inhibitors
1741:Harada, K.I., et al.,
1681:Briand, J.F., et al.,
1610:. N Engl J Med, 1998.
1589:Azevedo, S.M. et al.,
1342:Microcystis aeruginosa
876:
873:Microcystis aeruginosa
862:Microcystis aeruginosa
854:Microcystis aeruginosa
818:Microcystis aeruginosa
791:
765:-β-methyl-isoaspartate
1560:T. Nishizawa et al.,
1394:protein phosphatase 1
1353:Developmental effects
894:Mechanism of toxicity
870:
813:nonribosomal peptides
789:
2001:at Wikimedia Commons
1456:green coloured water
2242:Covalent inhibitors
2163:Debromoaplysiatoxin
1889:10.1155/2013/596429
1534:D. Tillett et al.,
827:polyketide synthase
490: g·mol
39:
2097:Cylindrospermopsin
1952:2017-03-12 at the
1853:Zegura. B, et al.
1655:(4604): p. 1383-5.
1593:Toxicology, 2002.
1308:0.0325 mg/kg
1227:animal experiments
968:Short-term effects
877:
792:
714:Infobox references
37:
2204:
2203:
1997:Media related to
1876:ISRN Microbiology
1651:. Science, 1983.
1334:intraperitoneally
1326:
1325:
1198:Microcystin alone
996:Long-term effects
798:
770:
764:
722:Chemical compound
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719:
624:Hazard statements
356:CompTox Dashboard
152:Interactive image
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1402:protein kinase C
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1322:0.06 mg/kg
1299:Intraperitoneal
1294:0.05 mg/kg
1285:Intraperitoneal
1271:Inhalation, 10h
1238:
1232:
1231:
1216:
1215:
1203:
1202:
1194:
1193:
1181:
1180:
1146:
1145:
1114:
1113:
1084:
1083:
1068:
1067:
1059:
1058:
1034:
1033:
1018:
1017:
1001:
1000:
973:
972:
948:
947:
943:Human poisonings
935:
934:
899:
898:
808:
807:
796:
768:
762:
749:
748:
704:
698:
695:
694:
651:
647:
643:
639:
635:
631:
603:
576:extremely toxic
489:
487:
472:
466:
460:
454:
447:Chemical formula
380:
379:
364:
362:
346:
326:
315:
301:
281:
252:
244:
233:
222:
202:
182:
165:MC-LR, MCYST-LR
154:
130:
102:
47:
40:
2257:
2256:
2252:
2251:
2250:
2248:
2247:
2246:
2217:Cyclic peptides
2207:
2206:
2205:
2200:
2182:
2178:Aetokthonotoxin
2116:
2083:
2040:
2035:
2005:
1989:
1986:
1985:
1980:
1975:
1971:
1963:
1959:
1954:Wayback Machine
1944:
1940:
1934:
1930:
1921:
1917:
1869:
1868:
1864:
1852:
1848:
1839:
1835:
1826:
1813:
1800:
1796:
1787:
1783:
1774:
1765:
1756:
1749:
1740:
1736:
1698:
1697:
1693:
1689:(4): p. 361-77.
1685:Vet Res, 2003.
1680:
1676:
1663:
1659:
1646:
1642:
1633:
1618:
1614:(13): p. 873-8.
1605:
1601:
1588:
1584:
1575:
1568:
1559:
1555:
1546:
1542:
1533:
1522:
1513:
1509:
1500:
1493:
1485:
1481:
1477:
1474:
1473:
1452:
1449:
1448:
1432:metalloprotease
1428:
1425:
1424:
1387:
1384:
1383:
1371:
1368:
1367:
1359:
1356:
1355:
1233:
1230:
1229:
1217:
1214:
1213:
1204:
1201:
1200:
1195:
1192:
1191:
1189:Carcinogenicity
1182:
1179:
1178:
1147:
1144:
1143:
1115:
1112:
1111:
1103:conjugated bond
1090:cytochrome P450
1085:
1082:
1081:
1069:
1066:
1065:
1060:
1057:
1056:
1035:
1032:
1031:
1029:Exposure Routes
1019:
1016:
1015:
1002:
999:
998:
983:gastroenteritis
974:
971:
970:
949:
946:
945:
936:
933:
932:
900:
897:
896:
847:protein domains
809:
806:
805:
750:
747:
746:
723:
716:
711:
710:
709: ?)
700:
696:
692:
688:
674:
668:
626:
612:
596:
573:
548:
545:
485:
475:
469:
463:
457:
449:
435:
432:
427:
426:
415:
412:
411:
405:
404:
401:
395:
394:
383:
365:
358:
349:
329:
316:
304:
284:
271:
262:
225:
205:
185:
157:
144:
133:
120:
106:
94:
38:Microcystin-LR
33:
32:
29:
28:
23:
22:
17:
16:
14:
13:
9:
8:
3:
2255:
2253:
2245:
2244:
2239:
2234:
2229:
2224:
2219:
2209:
2202:
2201:
2199:
2198:
2187:
2184:
2183:
2181:
2180:
2175:
2170:
2168:Lyngbyatoxin-a
2165:
2160:
2155:
2150:
2145:
2140:
2135:
2130:
2124:
2122:
2118:
2117:
2115:
2114:
2109:
2106:Microcystin-LR
2099:
2093:
2091:
2085:
2084:
2082:
2081:
2076:
2071:
2066:
2061:
2056:
2050:
2048:
2042:
2041:
2036:
2034:
2033:
2026:
2019:
2011:
2004:
2003:
2002:
1999:Microcystin-LR
1984:
1983:External links
1981:
1979:
1978:
1969:
1957:
1938:
1928:
1915:
1862:
1846:
1833:
1811:
1794:
1781:
1763:
1747:
1734:
1711:(2): 241–246.
1691:
1674:
1657:
1640:
1616:
1599:
1582:
1566:
1553:
1540:
1520:
1507:
1491:
1478:
1472:
1469:
1465:Eutrophication
1447:
1444:
1440:microcystinase
1423:
1422:Biodegradation
1420:
1382:
1376:
1366:
1363:
1354:
1351:
1324:
1323:
1320:
1317:
1314:
1310:
1309:
1306:
1303:
1300:
1296:
1295:
1292:
1289:
1286:
1282:
1281:
1280:18 mg/kg
1278:
1275:
1272:
1268:
1267:
1264:
1261:
1256:
1252:
1251:
1248:
1245:
1242:
1228:
1222:
1212:
1209:
1199:
1196:
1190:
1187:
1177:
1174:
1142:
1139:
1135:chemical burns
1127:hepatotoxicity
1117:Toxic effects
1110:
1107:
1080:
1077:
1064:
1061:
1055:
1052:
1030:
1027:
1014:
1013:Animal effects
1011:
997:
994:
969:
966:
944:
941:
931:
928:
920:phosphorylated
895:
892:
804:
801:
745:
742:
726:Microcystin-LR
721:
718:
717:
712:
690:
689:
685:standard state
682:
679:
678:
675:
666:
664:
661:
660:
653:
652:
627:
622:
619:
618:
613:
608:
605:
604:
597:
592:
589:
588:
578:
577:
574:
571:
568:
567:
558:
557:
553:
552:
549:
546:administration
542:
539:
538:
534:
533:
530:
521:
520:
517:
510:
509:
506:
500:
499:
496:
492:
491:
483:
477:
476:
473:
467:
461:
455:
450:
445:
442:
441:
437:
436:
434:
433:
430:
422:
421:
420:
417:
416:
414:
413:
409:
408:
406:
402:
399:
398:
390:
389:
388:
385:
384:
382:
381:
368:
366:
354:
351:
350:
348:
347:
339:
337:
331:
330:
328:
327:
319:
317:
309:
306:
305:
303:
302:
294:
292:
286:
285:
283:
282:
274:
272:
267:
264:
263:
261:
260:
256:
254:
246:
245:
235:
227:
226:
224:
223:
215:
213:
207:
206:
204:
203:
195:
193:
187:
186:
184:
183:
175:
173:
167:
166:
163:
162:Abbreviations
159:
158:
156:
155:
147:
145:
138:
135:
134:
132:
131:
123:
121:
116:
113:
112:
108:
107:
100:
96:
95:
60:
54:
53:
49:
48:
34:
31:
30:
26:
25:
21:
20:
18:
15:
12:
11:
10:
7:
6:
5:
4:
2:
2254:
2243:
2240:
2238:
2235:
2233:
2230:
2228:
2225:
2223:
2222:Cyanobacteria
2220:
2218:
2215:
2214:
2212:
2197:
2189:
2188:
2185:
2179:
2176:
2174:
2171:
2169:
2166:
2164:
2161:
2159:
2156:
2154:
2153:Cyanopeptolin
2151:
2149:
2148:Cyanobacterin
2146:
2144:
2141:
2139:
2136:
2134:
2131:
2129:
2126:
2125:
2123:
2119:
2113:
2110:
2107:
2103:
2100:
2098:
2095:
2094:
2092:
2090:
2086:
2080:
2077:
2075:
2072:
2070:
2067:
2065:
2062:
2060:
2057:
2055:
2052:
2051:
2049:
2047:
2043:
2039:
2032:
2027:
2025:
2020:
2018:
2013:
2012:
2009:
2000:
1995:
1991:
1990:
1982:
1973:
1970:
1967:
1961:
1958:
1955:
1951:
1948:
1942:
1939:
1932:
1929:
1925:
1919:
1916:
1909:
1905:
1900:
1895:
1890:
1885:
1881:
1877:
1873:
1866:
1863:
1860:
1856:
1850:
1847:
1843:
1837:
1834:
1830:
1824:
1822:
1820:
1818:
1816:
1812:
1808:
1804:
1798:
1795:
1791:
1785:
1782:
1778:
1772:
1770:
1768:
1764:
1760:
1754:
1752:
1748:
1744:
1738:
1735:
1728:
1724:
1719:
1714:
1710:
1706:
1702:
1695:
1692:
1688:
1684:
1678:
1675:
1671:
1667:
1661:
1658:
1654:
1650:
1644:
1641:
1637:
1631:
1629:
1627:
1625:
1623:
1621:
1617:
1613:
1609:
1603:
1600:
1596:
1592:
1586:
1583:
1579:
1573:
1571:
1567:
1563:
1557:
1554:
1550:
1544:
1541:
1537:
1531:
1529:
1527:
1525:
1521:
1517:
1511:
1508:
1504:
1498:
1496:
1492:
1488:
1483:
1480:
1470:
1468:
1466:
1462:
1457:
1445:
1443:
1441:
1437:
1433:
1421:
1419:
1417:
1413:
1412:
1407:
1403:
1399:
1395:
1391:
1380:
1377:
1375:
1364:
1362:
1352:
1350:
1347:
1343:
1339:
1335:
1331:
1330:intravenously
1321:
1318:
1315:
1312:
1311:
1307:
1304:
1301:
1298:
1297:
1293:
1290:
1287:
1284:
1283:
1279:
1276:
1273:
1270:
1269:
1266:5 mg/kg
1265:
1262:
1260:
1257:
1254:
1253:
1249:
1246:
1243:
1240:
1239:
1236:
1226:
1223:
1221:
1210:
1208:
1197:
1188:
1186:
1175:
1173:
1170:
1166:
1161:
1159:
1154:
1152:
1140:
1138:
1136:
1132:
1128:
1124:
1123:neurotoxicity
1120:
1108:
1106:
1104:
1098:
1095:
1094:cytochrome b5
1091:
1078:
1076:
1073:
1062:
1053:
1051:
1049:
1044:
1041:
1028:
1026:
1023:
1012:
1010:
1008:
995:
993:
990:
988:
984:
979:
967:
965:
963:
959:
955:
942:
940:
929:
927:
923:
921:
917:
913:
909:
905:
893:
891:
888:
886:
882:
874:
869:
865:
863:
859:
855:
850:
848:
844:
840:
836:
832:
828:
824:
820:
819:
814:
802:
800:
788:
784:
782:
778:
774:
766:
759:
755:
754:heptapeptides
743:
741:
739:
735:
734:cyanobacteria
731:
727:
715:
708:
703:
686:
680:
676:
672:
663:
662:
658:
654:
628:
625:
621:
620:
617:
614:
611:
607:
606:
602:
598:
595:
591:
590:
586:
584:
579:
575:
570:
569:
565:
564:
559:
554:
550:
547:
541:
540:
537:Pharmacology
535:
531:
529:
528:
523:
522:
518:
515:
512:
511:
507:
505:
502:
501:
497:
494:
493:
484:
482:
479:
478:
451:
448:
444:
443:
438:
429:
425:
418:
407:
397:
393:
386:
378:
374:
373:DTXSID3031654
370:
369:
367:
357:
353:
352:
345:
341:
340:
338:
336:
333:
332:
325:
321:
320:
318:
312:
308:
307:
300:
296:
295:
293:
291:
288:
287:
280:
276:
275:
273:
270:
266:
265:
258:
257:
255:
253:
248:
247:
243:
239:
236:
234:
232:ECHA InfoCard
229:
228:
221:
217:
216:
214:
212:
209:
208:
201:
197:
196:
194:
192:
189:
188:
181:
177:
176:
174:
172:
169:
168:
164:
161:
160:
153:
149:
148:
146:
142:
137:
136:
129:
125:
124:
122:
119:
115:
114:
109:
97:
92:
88:
84:
80:
76:
72:
68:
64:
59:
55:
50:
46:
41:
2173:Microviridin
2128:Aplysiatoxin
2105:
2102:Microcystins
2089:Hepatotoxins
2064:Antillatoxin
1972:
1960:
1941:
1931:
1923:
1922:Francis, G.
1918:
1879:
1875:
1865:
1858:
1854:
1849:
1836:
1806:
1802:
1797:
1789:
1784:
1776:
1758:
1742:
1737:
1708:
1704:
1694:
1686:
1682:
1677:
1672:(3): p. 403.
1669:
1665:
1660:
1652:
1648:
1643:
1635:
1611:
1607:
1602:
1594:
1590:
1585:
1577:
1561:
1556:
1548:
1543:
1535:
1515:
1510:
1502:
1486:
1482:
1453:
1436:Lake Rotorua
1429:
1409:
1389:
1388:
1378:
1372:
1365:Genotoxicity
1360:
1341:
1327:
1313:Intravenous
1234:
1224:
1218:
1205:
1183:
1162:
1155:
1148:
1131:cytotoxicity
1116:
1099:
1086:
1074:
1070:
1045:
1036:
1024:
1020:
1007:carcinogenic
1003:
991:
975:
950:
937:
924:
901:
889:
878:
872:
861:
857:
853:
851:
842:
838:
834:
830:
822:
816:
810:
803:Biosynthesis
793:
751:
738:microcystins
729:
725:
724:
656:
615:
582:
572:Main hazards
561:
526:
498:White solid
200:ChEMBL444092
111:Identifiers
99:Other names
90:
86:
82:
78:
74:
70:
66:
62:
2227:Cyanotoxins
2143:Coibamide A
2138:Caldoramide
2133:Apratoxin A
2046:Neurotoxins
2038:Cyanotoxins
1634:WHO (2003)
1597:: p. 441-6.
1416:clastogenic
1411:Microcystis
1396:(PP-1) and
1338:hepatocytes
1119:cyanotoxins
1063:Disposition
978:hepatotoxic
885:phenylgroup
671:median dose
657:Lethal dose
610:Signal word
566:(OHS/OSH):
516:in ethanol
508:1.299 g/cm
495:Appearance
440:Properties
238:100.150.186
128:101043-37-2
2211:Categories
2074:Kalkitoxin
2059:Guanitoxin
2054:Anatoxin-a
1471:References
1165:epithelium
1158:hemorrhage
1088:levels of
1079:Metabolism
1048:food chain
594:Pictograms
551:Ingestion
514:Solubility
481:Molar mass
344:EQ8332842Y
269:IUPHAR/BPS
211:ChemSpider
180:CHEBI:6925
139:3D model (
118:CAS Number
58:IUPAC name
2158:Cyclamide
2112:Nodularin
2079:Saxitoxin
1346:neoplasms
1244:Toxicity
1167:of nasal
1040:half-life
744:Structure
585:labelling
544:Routes of
259:621-323-9
251:EC Number
2196:Category
1950:Archived
1908:23936728
1727:10713428
1390:In vitro
1379:In vitro
1247:Species
1109:Toxicity
962:dialysis
781:arginine
677:5 mg/kg
556:Hazards
519:1 mg/mL
324:24896778
1899:3712209
1882:: 1–8.
1859:116-122
1805:in vivo
1595:181-182
1446:History
1381:studies
1225:In vivo
954:Caruaru
930:Effects
777:leucine
707:what is
705: (
504:Density
488:995.189
311:PubChem
220:4941647
2104:(e.g.
1906:
1896:
1725:
1319:Mouse
1305:Mouse
1277:Mouse
1263:Mouse
1250:Value
1169:mucosa
958:Brazil
883:- and
881:acetyl
831:mcyA-E
702:verify
699:
616:Danger
532:-1.44
424:SMILES
299:C05371
191:ChEMBL
52:Names
2232:Algae
2121:Other
1316:LD50
1302:LD50
1288:LD50
1274:LC50
1255:Oral
1133:with
916:block
815:. In
730:MC-LR
392:InChI
171:ChEBI
141:JSmol
2069:BMAA
1904:PMID
1880:2013
1723:PMID
1398:PP2A
1291:Rat
1259:LD50
1129:and
1092:and
985:and
908:PP2A
906:and
858:mcyG
841:and
839:mcyF
833:and
779:and
760:and
758:ADDA
650:H335
646:H319
642:H317
638:H315
634:H310
630:H300
525:log
335:UNII
290:KEGG
279:4735
1894:PMC
1884:doi
1713:doi
1709:184
1653:220
1612:338
1404:or
1332:or
904:PP1
843:H-J
823:mcy
583:GHS
361:EPA
314:CID
89:,22
85:,19
81:,18
77:,15
73:,12
69:,11
2213::
1902:.
1892:.
1878:.
1874:.
1814:^
1766:^
1750:^
1721:.
1707:.
1703:.
1687:34
1619:^
1569:^
1523:^
1494:^
1430:A
1125:,
1105:.
989:.
956:,
783:.
740:.
667:50
665:LD
648:,
644:,
640:,
636:,
632:,
587::
474:12
468:10
462:74
456:49
101:5-
65:,8
61:(5
2108:)
2030:e
2023:t
2016:v
1910:.
1886::
1729:.
1715::
1670:5
875:.
835:G
797:D
769:D
767:(
763:D
728:(
697:N
673:)
669:(
527:P
471:O
465:N
459:H
453:C
363:)
359:(
143:)
103:L
91:R
87:S
83:S
79:S
75:S
71:R
67:S
63:R
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