If Odor Is Lock-and-Key, What Happens When You Change All the Locks?
Material below summarizes the article Vibrational Detection of Odorant Functional Groups by Drosophila Melanogaster, published on October 26, 2017, in eNeuro and authored by Klio Maniati, Katherine-Joanne Haralambous, Luca Turin, and Efthimios M.C. Skoulakis.
We are interested in tests that could help decide between the vibrational theory of odor and the lock-and-key theory, a controversial question in the field of olfaction. Is odor character of a molecule determined by its shape or its vibrations?
In a shape theory, the smell of an odorant is encoded in the shape of the odorant molecule, which in turn determines the receptors in which it fits. This is a lock-and-key theory: the shapes of both locks and keys matter to the pattern of receptor activation.
Picture a thought experiment in which the shapes of the olfactory receptor binding sites are all altered, while leaving wiring identical to the brain. The receptor activation pattern will be different, and therefore odorants will be perceived to have a different smell or odor character.
In a vibration theory, the smell of an odorant is encoded in the molecular vibrations of the odorant itself. The large number of smell receptors present makes sure enough of them bind any given odorant so relevant bands of the odorant’s vibrational spectrum are probed, as in color vision.
Now do the same thought experiment and change the shape of all receptors. Odorants will now also bind to a different set of receptors, but if there are enough of them in each band binding the odorants, the spectrum bands will be correctly measured and the odor will remain the same.
This is a fundamental difference that could experimentally test the correctness of one or the other theory. Altering the binding sites of all receptors is not possible at the moment, because we do not exactly know where odorants bind. However, we can ask whether animals endowed with receptors of completely different shapes perceive odorants in a similar fashion.
Insect odorant receptors are completely different from mammalian ones: They have no sequence homology and a different topology. Do fruit flies smell things the way we do? Which odorants should be used to test this? To keep the test simple and reduce the problem to a single vibrational band, we used two remarkable observations taken from human olfaction.
(1) One of the most remarkable coincidences in olfaction is that both sulfur and boron hydrides (respectively known a thiols and boranes) — and nothing else in nature — smell sulfuraceous to us despite having no chemical properties in common. What they have in common, however, is a stretch (B-H vs S-H) vibrational frequency, around 2600 cm-1.
Do flies then perceive boranes to smell like sulfur? Our experiments show the answer appears to be yes, as flies trained to avoid boranes then avoid thiols and vice versa. This suggests that they are detecting a vibration at the same frequency.
(2) A second experiment involves the intensity, rather than the frequency, of a vibration. It is well known in cyanohydrins, chemical structures in which a nitrile (-CN) and a hydroxyl (-OH) group are attached to the same carbon, the distinctive CN stretch vibration shows up very weakly in spectrometers. Interestingly, cyanohydrins also lack the distinctive "nitrilic" odor character imparted to any odorant by the -CN group. If the -OH group is moved one carbon away, both the -CN vibration intensity and the -CN odor are restored.
We tested how flies trained to avoid a nitrile respond to a cyanohydrin and its displaced congener. Our results show flies, like us, do not perceive the nitrile in cyanohydrins but do perceive it when the -OH is moved.
We therefore conclude that in these two cases at least, odor character is determined not by shape but by molecular vibrations.
Vibrational Detection of Odorant Functional Groups by Drosophila Melanogaster. Klio Maniati, Katherine-Joanne Haralambous, Luca Turin, and Efthimios M C Skoulakis. eNeuro Oct 2017 DOI: https://doi.org/10.1523/ENEURO.0049-17.2017