Olfaction: Does the key still fit the lock?

Welcome back, Beer Readers! I’ll kick off 2011 with a brief [read: “half-assed”] discussion about the current level of understanding about how smell works.

Frankly, the sensation of smell is poorly understood. Specifically, the uncertainty is focused on how the receptors are stimulated by the odorant; the actual mechanisms behind how the resulting signal is carried to the brain is fairly well established (we’ll discuss gustducin and G-protein-coupled receptors more in the future).

For many years, olfaction has been described as a receptor-based system with aromatic molecules stimulating specific receptors in the olfactory bulb. This system has been called the “lock and key” model, since each receptor responds to only one “key” molecule. In this model, the differences in size and shape of a molecule is what allows the receptors to differentiate between odorants. There are some shortcomings in this model, however. Some molecules which are very similar in size and shape can have startlingly different aromas. Also, if one receptor matches one odorant, then how is it that can we identify many thousands of individual aromas when the human genome only has 350 genes which code for olfactory receptors? [By comparison, mice have 900 olfactory receptor genes which code for about 1200 individual receptors; or about 1200 different aromas, in the lock and key model.]

New research (and by “new” I mean within the last 15 years) descibes a much more complex picture of what is going on, and some follow-up research demonstrates that this new model has some real potential. What the new model posits is that, when the odorant molecule binds to the receptor, inelastic electron tunneling takes place where an electron is transferred from the from the donor molecule to the receptor, in a non-redox process (it can do this due to its ability to act like both a wave and a particle). This “activates” the receptor and allows it to “read” the vibrational energy within the odorant molecule. These vibrations can apparently vary rather significantly due to very slight changes in the structure of the molecule, which agrees with the observations that similar molecules can show different characteristic aromas. This could theoretically imply that a single receptor could might be able to associate with a number of different molecules, each one being seen as unique due to the differing amounts of vibrational energy they carry. But this quantum physics stuff starts to get a bit over my head (I’m more of a chemist), so I’ll just let this other WordPress blog post from 12/2006 describe this research.

I just love it when we find out that things are far more interesting, complex, and nuanced than we previously thought. It just re-affirms that we can’t become complacent about our level of understanding of the world, since you never know when the apple cart will be upturned and years of scientific understanding need to be re-assessed.

Happy New Year, hope your holidays went well, and see you next time! Prost!


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