When you think of a toxin or poison, what do you think of? Anthrax? Ricin? Venom? How about a amino acid? Twenty-one years ago this month, Christopher McCandless died due to being poisoned by an amino acid, beta-N-oxalyl-L-alpha-beta diaminopropionic acid, which is a structural analogue to glutamate.Who is Christopher McCandless? He was the inspiration for the book "Into the Wild," and for many years was thought to have died from strictly starvation. In one of his last journal entries, Mr McCandles speaks of feeling weak and ill and blames is on the "Pot[ato] seed" he was ingesting. This fact was originally discredited as plant toxins are often come in the forms of an alkaloid. The seeds of the wild potato, Hedysarum alpinum, were tested no toxic alkaloids were found.
So, no alkaloid no toxin right? Wrong. What Hedysarum alpinum does have is .394 percent beta-N-oxalyl-L-alpha-beta diaminopropionic acid, more commonly known as ODAP, by weight. This compound affects each individual differently, however, the group at highest risk is physically active young males with a limited diet. Christopher unknowingly sealed his own fate by being a young male, living meagerly off the land, being physically active (hiking, hunting, etc) and ingesting a plant that was thought to be non- toxic.
However, this compound is not new. Records show that the Nazi Concentration camp Vapniarca experimented with a similar amino acid of the wild grass pea. The seeds were made into bread and fed to the inmates. The prisoners over time developed paralysis from over stimulation of neurons. Sadly, once the condition started, it could not be reversed. This condition is referred to as "neurolathyrism", or more commonly, “lathyrism.”Although what happened to Mr. McCandless is very sad, it is a good reminder of how much we do not yet understand about the world around us.
References/Further readings:
http://www.christophermccandless.info/Ronald-Hamilton/ronald-hamilton-intothewild1.html
http://www.scribd.com/doc/166341536/The-Silent-Fire
http://www.newyorker.com/books/page-turner/how-chris-mccandless-died
James this is very interesting! The first thing that I was thinking about is the mode of beta-N-oxalyl-L-alpha-beta diaminopropionic acid inhibition since it is a structural analog to glutamate. It seems like because it may have a higher affinity for the target receptor it competitively inhibits glutamate but irreversibly. Also surprising was that this compound leads to paralysis due to overstimulation because we typically think of paralysis as the failure to transmit a signal for a number of reasons. Though this amino acid is toxic, I wonder if experimentally it could have beneficial effects at lower doses just like the botulinum toxin. Overall as you mentioned, this just goes to show you that we still have a lot more learning to do about the world around us whether it involves discovering toxic or therapeutic compounds.
ReplyDeleteI too found this article to be pretty interesting, especially among the realm of structural analogs to compounds found in our body. As you may be aware, glutamate is the most prominent neurotransmitter found in our body, and is mainly excitatory. I had no idea that certain precursors and analogs that are needed in our body could also be found to exhibit negative effects, such as beta-N-oxalyl-L-alpha-beta-diaminopropionic acid. What is also interesting is the fact that these precursors and analogs have been found to affect individuals differently, especially based on one's lifestyle.
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