Copyright 1997 Mark Thorson

Super Blue Green (registered trademark, Cell Tech brand) algae is the species known as _Aphanizomenon_flos-aquae_.

The remainder of this file is divided into five parts:

PART I. What are microcystins?

Quoting from _Toxicon_, volume 32, number 12, "Use of a Colorimetric Protein Phosphatase Inhibition Assay and Enzyme Linked Immunosorbent Assay for the Study of Microcystins and Nodularins.", by An and Carmichael, 1994, pages 1495 and 1496:

"Microcystins are monocyclic heptapeptide liver toxins produced by species of cyanobacteria within the genera _Microcystis_, _Anabaena_, _Oscillatoria_, and _Nostoc_ (Carmichael, 1992). The toxins contain two variable L-amino acids plus three D-amino acids plus the unusual amino acids, N-methyldehydroalanine and 3-amino-9-methoxy- 10-phenyl-2,6,8-trimethyl-deca-4(E)6(E)-dienoic acid (Adda) (Reinhart _et_al_, 1988)."

[A peptide is a small protein. A heptapeptide is a protein composed of seven amino acids. Monocyclic means it's a one-ring loop. A microcystin is a seven-member ring of amino acids, containing three D-amino acids and two weird amino acids, neither kind normally being found in human food. Amino acids can have two mirror-image forms, called D and L. All amino acids used to build proteins in the human body are L-amino acids, except glycine which is reflection-symmetric (i.e. neither D nor L). D-amino acids are nutritionally inert, and they may contribute towards the ability of microcystins to survive the digestive process intact and get absorbed.]

Quoting from page 1497:

"Recently, both microcystin and nodularin have been found to be potent inhibitors of protein phosphatase types 1 and 2A (Yoshizawa _et_al_, 1990) as well as tumor promoters in laboratory animals (Nishiwaka-Matsushima _et_al_, 1992b; Falconer, 1991). They are also suspected to be involved with promotion of primary liver cancer in humans exposed to long-term low doses of these cyclic peptide toxins through drinking water (Carmichael, 1994; Yu, 1989)."

PART II. Where do microcystins come from?

Quoting from "A Cell Tech Statement Regarding _Microcystis_ in Klamath and Agency Lakes", Cell Tech press release, September 1996:

"Cell Tech also closely monitors algal blooms in Klamath and Agency Lakes by regularly performing species identification and quantification."

"Our test results indicate that there is currently a high level of _Microcystis_aeruginosa_ in certain parts of the lake, particularly Agency Lake."

[Cell Tech claims their standard is no more than 1% non-_Aphanizomenon_ species in SBGA.]

Quoting from "A Message from Christian Drapeau", a file posted by Jim Fentress ( on April 8, 1996,:

"Microcystins are regularly found, but only in non- significant amounts (specifically, 0.1-0.2 mcg/g of SBGA)."

Quoting from a posting made on May 25, 1997, <>, from Bluuegreen :

From Wright State University, Dept. of Bio. Sciences,


(513-873-2655 FAX: 513-873-3320)

ELISA assay for ... microcystins:

Measurable levels of microsystin or nodularin were found

in samples QA-9638 - QA-9643 (ug/g):

638    1.1

639    0.4

640     1.3

641     1.0

642     1.7

643     0.7

[Note that these numbers are about ten times higher than those admitted in the previous quote.]

Quoting from "Response to Vegetarian Times", a letter from Marta Kollman, October 31, 1996, available on Cell Tech's fax-on-demand service (800/565-5092) as document #151:

"We know from rigorous testing over the years that _Microcystis_ has always existed in Klamath Lake at very low levels."

[But how low is low enough? Read on!]

PART III. What do microcystins do?

Quoting from _Journal_of_Cancer_Research_and_Clinical_ _Oncology_, volume 118, "Liver Tumor Promotion by the Cyanobacterial Peptide Toxin Microcystin-LR", by Nishiwaki-Matsushima, Ohta, Nishiwaki, Suganuma, Kohyama, Ishikawa, Carmichael, and Fujiki, 1992, page 421:

"In two experiments, we found that microcystin-LR has a potent tumor-promoting activity in rat liver initiated with diethylnitrosamine (DEN) below the concentrations that do not release aminotransferase (transaminase) from the liver into the blood serum. Microcystin acts on the liver through the okadaic acid pathway and is one of the strongest liver tumor promoters found to date."

[DEN is a carcinogen used to seed cancer foci in the experimental animals. Once seeded, the experiment measured the promotion of these cancer foci by various suspected tumor promoters. Release of aminotransferase into the blood would be a sign of an acutely hepatotoxic reaction, which microcystins may cause. This set of experiments found potent liver tumor promotion at levels below those which are acutely or sub-acutely toxic to the liver, as indicated by the lack of release of aminotransferase.]

Quoting from page 423:

"The mechanism of action of microcystin in liver cells is similar to that of okadaic acid, and therefore most likely expressed through the okadaic pathway. We have found that the okadaic pathway, involving inhibition of protein phosphatase 1 and 2A activities, is a general mechanism of tumor promotion in various organs."

[Inhibition of PP1 and PP2A ain't good!]

PART IV. Is any level of microcystins safe?

Quoting from _Biochemical_Journal_, volume 306, "Inhibition of Specific Binding of Okadaic Acid to Protein Phosphatase 2A by Microcystin-LR, Calyculin-A and Tautomycin: Method of Analysis of Interactions of Tight-Binding Ligands with Target Protein", by Takai, Sakai, Nagai, Mieskes, Isobe, Isono, and Yasumoto, 1995, page 662:

"Of the protein phosphatase inhibitors examined, microcystin-LR exhibited the highest affinity to PP2A."

"Of the inhibitors examined, it was also microcystin-LR that exhibited the highest affinity for PP1."

[A tight-binding ligand is a molecule that holds on to a binding site of an enzyme so strongly it seldom lets go. In this paper, the rate constants for binding of toxins to PP2A were about 10 to 100 billion times greater than their dissociation constants.]

[That's a big difference in favor of binding! For all practical purposes, binding is irreversible. Even at low levels of exposure, the PP1 and PP2A enzymes suck up the toxin and keep it. Can any long-term exposure be safe, if liver enzymes are accumulating the toxin?]

Quoting from _Biochemical_and_Biophysical_Research_ _Communications_, volume 216, number 1, "_In_Vivo_ and _in_Vitro_ Binding of Microcystin to Protein Phosphatases 1 and 2A", by Runnegar, Berndt, Kong, Lee, and Zhang, 1995, page 162:

"Microcystins are normally cell impermeant, but they accumulate in the liver by specific carrier-mediated transport in hepatocytes which results in PP inhibition and toxicity."

[Hepatocytes are liver cells. Microcystins accumulate in liver cells.]

Quoting from pages 167 and 168:

"We have shown that microcystin, a potent and specific inhibitor of PP1 and PP2A activity, is covalently bound to both PP1 and PP2A catalytic subunits in hepatocytes incubated with the toxin."

[This paper explains why the binding of microcystins to liver enzymes is virtually irreversible. Most molecules bind to enzymes because of close fit. The enzyme will have a pocket shaped like the molecule, and the molecule will fit into that pocket like a key fitting into a lock. Microcystins are unusual in that they form covalent bonds to their binding sites on liver enzymes. This is like a key which not only fits the lock, but also proceeds to weld itself to the lock.]

PART V. How can algae users protect against microcystins?

Cell Tech claims to use sophisticated biochemical tests that can monitor the level of microcystins in the algae harvested from Klamath Lake. Cell Tech says every batch is tested to ensure it is "below guideline levels" of microcystins. But to my knowledge, Cell Tech has never stated publicly what these levels are. They're not zero, obviously, or Cell Tech would say they're zero. And how did Cell Tech establish these guideline levels? What literature can Cell Tech cite that says these levels are safe?

SBGA users who are concerned about the possibility of exposure to microcystins should ask their upline these questions.