Tuesday, August 5, 2008

Hear me now, smell me later

From a very cool 2007 review of current findings in olfaction: The scent of life. The exquisite complexity of the sense of smell in animals and humans
(EMBO reports 8, 7, 629–633 (2007) doi:10.1038/sj.embor.7401029)

CO2-sensitive neurons expressing Gr21a (green) and Gr63a (red), proteins that together are necessary for CO2 detection in Drosophila. The neurons target a specific region of the fly brain, which is dedicated to processing the smell of CO2. Credit: Vosshall Laboratory, Rockefeller University. Reprinted with permission from Macmillian Publishers Ltd [Nature, Jones et al, 2007].

Participation in the Vosshall lab's study on the Physiological Effects of Androstadienone Exposure is open on the RUCares site. I haven't had a chance to participate in any of her experiments but they sound like a great way to get in touch with one's own olfactory perception.

The scent of life
article offers an excellent summary of the controversy surrounding Luca Turin's controversial model for understanding odorant receptors.

The major model is the odotope theory where the shape of the odorant determines the selective binding to the receptor. Only a small portion of the odorant binds so it is possible for different odorant molecules to activate the same receptor, and potentially for a single odorant molecule to activate multiple receptors depending on the contact point.

In contrast, Luca Turin's model proposes that when an odorant comes in contact with a receptor with a congruent vibrational pattern, the electrons jump to a higher energy state activating the receptor. I confess that I don't know much about electron tunneling, the main phenomenon behind his theory, but I have never heard of it as part of a biological phenomenon. Electron tunneling offers extremely cool applications in bio-imaging, and electron excitation is the physics behind modern fluorescence microscopy, but I have never heard of it as part of a biological system - which doesn't mean that it's not true, but it's significantly more complicated than the predominant model and does not seem to explain certain biological phenomena. For example, it doesn't seem to explain why the chirality of molecules would have such a large impact on our perception of their odor.

R Carvone smells like spearmint, S Carvne smells like carraway.

For example, let's look at Carvone , a simple ring structure that's frequently used in Organic Chemistry texts as an example of chirality or "handedness". When a molecule and it's mirror image (or enantiomer) cannot be superimposed, they are said to be chiral. For example, looking at your left hand, your right hand would be it's mirror image or enantiomer, but you can't superimpose them. Right hand sure looks like the left hand, but they are not conformationally the same as anyone who's ever tried to jam their left hand into their right glove will attest. And this can at least in part explain the difference in odorant receptors - if you have a left glove shaped receptor protein, it's going to be activated preferentially by left hands, though as the jamming experiment dictates you might have some success trying to force a right hand in there.

So this is my simplistic understanding of odorant receptors - that we can smell thousands of scents based on the activation of only 400 types of odorant receptors because the specificity is low enough that many odorants activate multiple receptors. It's this pattern of activated receptors that is translated by the brain into what we understand as smell.

No discussion of science is ever complete without a picture of Jeff Goldbulm (or possibly Alan Alda. In this case, his role in The Fly is an homage to the humble Drosophila who have assisted the Vosshall lab in illuminating the neural anatomy of olfaction. Any and all tributes to Erik Kandel will feature Mr. Goldblum's famous line from Annie Hall: "I forgot my mantra."

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