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| Castor Bean Plant |
Ricin has recently been in the news because suspicious mail
was sent to Trump and top military advisors early in October. Initial tests of
the letters confirmed the presence of ricin, although there is conflicting
reporting on whether or not the compound identified was actually ricin or if it
contained “the natural ingredients to make ricin.” Nobody was hurt, and someone
was arrested for sending the letters, however, attempted ricin poisoning of
politicians is not uncommon.
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| The seeds of the castor plant: castor "beans" |
So, what is ricin and why is it toxic?
Ricin is a protein that comes from the castor bean plant.
The seeds of the plant, Ricinus communis,
are referred to as beans. When chewed, the seed releases ricin. It can also be
released when the seeds are processed for castor oil, but there is no ricin in
the oil. Ricin can be dangerous as a powder, pellet or mist. In fact, a
Bulgarian dissident was killed via a pellet of ricin shot into his leg. The
reason that ricin can be toxic via a letter is that the fine powder is easily
inhaled.
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| Ricin: a heterodimer protein. Chain A in purple. Chain B in orange. Disulfide linkage in green. PDB:2aai |
Ricin is a two-part toxin, meaning that one subunit of the
protein, the B chain, is the targeting mechanism, and the other subunit, the A
chain, is toxic. The B chain binds to carbohydrates on the surface of cells which
chaperone half of the protein into the cell. A disulfide bond between the A and
B chains is broken and only the A chain is transported into the cell. Once
inside the cell, ricin inactivates 1500 ribosomes per minute and kills the
cell. Average cells have anywhere from several thousand to 10 million
ribosomes, so ricin can take a few days to kill a human, but one molecule of
ricin can kill a whole cell.
An important feature of ribosomes that is essential for binding of elongation factors is called the sarcin/ricin loop. Ricin is a hydrolase which cuts off an adenine in the sarcin loop which permanently inactivates the ribosome. Ricin can then act on another ribosome until every single one in the cell is ruined. Some argue that depurination of ribosomes alone is not sufficient to account for the cytotoxicity of ricin, but there is little known about its exact mechanism.
Ricin isn’t all bad, though. Scientists can attach the ricin
A chain to an antibody that is specific for cancer cells. Only one immunotoxin
is approved for use in the treatment of cancer, specifically cutaneous T-cell
lymphoma. It contains a truncated version of the diphtheria toxin.
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| Antibody (yellow) linked to ricin A chains (red) PDB |
https://www.usatoday.com/story/news/2018/10/03/poisoned-letters-sent-white-house-had-ricin-element-arrest-made/1516061002/
R. J. Kreitman (2006) Immunotoxins for targeted cancer
therapy. AAPS Journal 8, E532- E551.
Ribosome Depurination Is Not Sufficient for
Ricin-Mediated Cell Death inSaccharomyces cerevisiae Xiao-Ping Li, Marianne
Baricevic, Hemalatha Saidasan, Nilgun E. Tumer
Very interesting topic. Very good title and graphics. Quite a good explanation of the chemistry. Interesting to note the chemotherapy application. It would be helpful to include links to your sources in the text. Good general interest source and good relevance to the news.
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