Theories of smell – Molecule Shape and Smell

Vibrational theory

In the screencast, we mention the two proposed theories for the mechanics of scent recognition; vibration theory and shape theory (or the lock and key model). The mechanics behind both of these theories still aren’t fully understood and there are unanswered questions surrounding both theories.

How does vibrational theory work?

Our noses have olfactory receptors that are used to distinguish different scents. The vibrational theory explanation for how this occurs is that atoms are joined together by bonds that are able to vibrate at specific frequencies; these vibration frequencies must be turned into, and delivered to the brain, as electrical signals. The ability to distinguish between different scents occurs due to the activation of specific olfactory pathways by the specific vibration energies of different bonds within different odour molecules.

Therefore, while the lock and key model proposes that if molecules have similar structures they will smell the same, the vibrational model states that molecules with bonds that have similar frequency vibrations will have the same scent.

A recent study

Recent studies examining the extent of isotopomer discrimination in honeybees, suggest that shape theory might not be enough to fully explain the ability of the honeybees to distinguish between odour compounds. Isotopomers (also known as isotopic isomers) are versions of the same molecule, with identical numbers of each element and isotope, but with differences in their positions. Isotopomer discrimination is the ability to register differences in the isotopomer odour molecules.

The study used undeuterated and deuterated versions of the same molecules. One of these odour molecules was acetophenone; shown below are the undeuterated (contains H atoms) and fully deuterated (all H atoms replaced by D atoms) versions of acetophenone.

Deuterated molecules are molecules where some, or all, of the hydrogen atoms (H) in the compound are replaced with deuterium (D), which is a stable isotope of hydrogen. The mass of deuterium is approximately double that of hydrogen, which leads to the deuterated and undeuterated molecules having almost identical shapes but significant differences in the stretching frequencies of the C–H and C–D bonds. This results in the C–H and C–D bonds having different specific vibration energies, suggesting that the undeuterated and deuterated molecules will activate different olfactory pathways to the brain, hence registering as different scents.

This was found to be the case when the scientists studied the effects of deuterated and fully undeuterated versions of acetophenone on the activation pathways in honeybees. The analysis determined that there were differences in pathway activation when deuterated molecules of acetophenone were used compared to the undeuterated version; leading to the conclusion that the lock and key model of olfaction might not be able to explain the observed distinction between deuterated and undeuterated acetophenone odour molecules by honeybees.

This study doesn’t provide conclusive proof that vibrational theory is the mechanism of odourant reception, as the deuteration ultimately affects more than the vibrational spectrum of the odour molecules. However, it does provide a basis for the assumption that the vibrations of molecules play a part in the odourant-receptor interactions. The true mechanism of scent reception is still indefinable, but this study does suggest that vibration theory is not to be sniffed at!

Cracking the olfactory code

In 2015, a $15 million project, sponsored by the National Science Foundation and the White House Brain Initiative, called Cracking the Olfactory Code was initiated. Scientists hope to unravel how smell (the oldest guidance system in the world) works. Then, the team aims to teach robots how to smell!

A life changing experience

If we don’t have receptors for an odour molecule, can new ones be created? We know there is large genetic variability within and between populations for our ability to detect odours. For example, research has shown that populations from Africa tend to be able to smell androstenone (a steroid found in boar’s saliva), while those from the northern hemisphere tend not to. To smell androstenone people need a gene that produces the OR7D4 receptor. Statistical analysis of the OR7D4 gene from around the world suggest that the different forms of this gene might have been subject to natural selection. Such research shows how global studies of our genes can give an insight into how our taste for different foods may have been influenced by variation in our ability to smell. So, yes, human receptors can evolve.

Keen sense of smell

So, who has the keenest sense of smell, dogs or humans? Research suggests that, in some cases, our sense of smell rivals that in dogs. For example, we are more sensitive to amyl acetate (pentyl ethanoate), CH₃CO₂(CH₂)₄CH₃, in bananas than dogs. This is likely explained by identifying ripe fruit being more important to our own ancestors and irrelevant to those of dogs.

On a related subject, have you heard about canine cancer detection? Recently, four Beagles were shown to be able to distinguish, by smell, between the blood of healthy people and those with lung cancer with ~97% accuracy. Cancerous cells have been reported to emit unique odours (for example, heptanal, CH₃CH₂CH₂CH₂CH₂CH₂CHO, in blood, urine or breath is often quoted as being indicative of certain types of cancers) and it is thought that these can be detected by the dogs. However, more work is needed to verify these and related results. It also raises the intriguing possibility of being able to recognise a specific disease from a breath-print of exhaled substances – perhaps, in the future, this will provide a suitable and reliable method of diagnosing an illness. (Rodent fans may also like to know that rats are now being used to detect tuberculosis from sputum samples. They are much quicker and more accurate (and cheaper!) than a lab technician with a microscope.)

Finally, on the subject of blood, the metallic aroma is caused by a compound called trans-4,5-epoxy-(E)-2-decenal, or TED. Interestingly, the odour of TED is attractive to top predators like tigers and wolves (perhaps this helps them find their prey), but it is aversive to prey species like mice and rats (perhaps this conveys information about predation and injury). TED is a chiral compound. Both enantiomers have been prepared separately in the lab and each has been smell tested. A panel of flavour scientists perceived each enantiomer to smell similarly, but one to be much more pungent than the other. The results using mice were particularly interesting as the individual enantiomers of TED did not communicate fear in the mice – it was only when they were mixed together that the mice became scared. Fascinating!