The swipe card model of odorant recognition

Abstract

Just how we discriminate between the different odours we encounter is not completely understood yet. While obviously a matter involving biology, the core issue isa matter for physics: what microscopic interactions enable the receptors in our noses-small protein switches—to distinguish scent molecules? We survey what is and is not known about the physical processes that take place when we smell things, highlighting the difficulties in developing a full understanding of the mechanics of odorant recognition. The main current theories, discussed here, fall into two major groups. One class emphasises the scent molecule's shape, and is described informally as a "lock and key" mechanism. But there is another category, which we focus on and which we call "swipe card" theories:the molecular shape must be good enough, but the information that identifies the smell involves other factors. One clearly-defined "swipe card" mechanism that we discuss here is Turin's theory, in which inelastic electron tunnelling is used to discern olfactant vibration frequencies. This theory is explicitly quantal, since it requires the molecular vibrations to take in or give out energy only in discrete quanta. These ideas lead to obvious experimental tests and challenges. We describe the current theory in a form that takes into account molecular shape as well as olfactant vibrations. It emerges that this theory can explain many observations hard to reconcile in other ways. There are still some important gaps in a comprehensive physics-based description of the central steps in odorant recognition. We also discuss how far these ideas carry over to analogous processes involving other small biomolecules, like hormones, steroids and neurotransmitters. We conclude with a discussion of possible quantum behaviours in biology more generally, the case of olfaction being just one example. This paper is presented in honour of Prof. Marshall Stoneham who passed away unexpectedly during its writing.

Figure 1.

Contrast these three odorants: according to shape theory, which would you predict smell the same? From left to right; cis -ketone (4-(4-tert-butylcyclohexyl)-4-methylhexan-2-one), cis-nor-ketone (4-(4-tert-butylcyclohexyl)-4-methylpentan-2-one) and 5α-androst-16-en-3-one . Cis -ketone and 5α-androst-16-en-3-one have the same “penetrating urine odour” and cis-nor-ketone is practically/totally odourless [21].

Figure 2.

A scheme for the proposal of electron transfer in the olfactory receptor. Only 5 transmembrane helices (of the 7 in total) for the olfactory receptor are shown (cylinders) here for clarity. (a) The odorant approaches the receptor, meanwhile an electron moves to position RD on a helix; (b) The odorant docks at the ligand binding domain, the overall configuration of receptor and odorant changes, meanwhile the electron tunnels within the protein to D and it spends some time there; (c) The electron jumps from D to A causing the odorant to vibrate; (d) The odorant is expelled from the ligand binding domain and the electron tunnels within the protein to site RA. Signal transduction is initiated with the G-protein release.

Figure 3.

A scheme for the proposal of electron transfer in the olfactory receptor with intra-protein electron transfer. Only 5 transmembrane helices for the olfactory receptor are shown (cylinders) here for clarity. (a) The odorant approaches the receptor, meanwhile an electron is present at donor site D; (b) The odorant docks at the ligand binding domain, the overall configuration of receptor and odorant changes (c) The electron jumps from D to A, causing the odorant to vibrate (d) The odorant is expelled from the ligand binding domain.

Figure 4.

A configuration coordinate diagram to show the initial state (the left curve) and the final state (the right curves) where there are two options: the inelastic (n = 1) versus the elastic (n = 0) route.

Figure 5.

A plot to show the time (s) for an inelastic transmission (red, thin line) versus the elastic transmission (pink, thick line) all parameters given in the table are constant, the variable is the reorganization energy λ.

Figure 6.

Acetophenone and acetophenone-d8.

Figure 7.

Sulphur compounds p-menthene-1-en-8-thiol and a stereoisomer. The latter smells 100,000 times weaker [55].

Figure 8.

Eugenol (EG) (left) is an agonist of olfactory receptor MOR-EG, methyl-isoeugenol (MIEG) (middle) is an antagonist and methyl-eugenol (MEG) (right) is an agonist.

Figure 9.

Hydrogen sulphide (left) and decaborane (right). Both smell sulphurous.

Figure 10.

Ferrocene (left) smells “spicy” versus nickelocene (right) smells “oily-chemical”.

Figure 11.

Hexanal, smell changes with increasing concentration.

Figure 12.

2 Nootkatones: the 4R, 4aS, 6R(+) enantiomer (left) smells of grapefruit (odor threshold 0.8 ppm) and its mirror is “woody, spicy” (threshold 600 ppm) [60]. Note also the (+)-enantiomer is around 750 times more potent odorant than the (−)-enantiomer [61].

Figure 13.

Type 1, tetrahydronootkatones smell “dusty-woody, fresh, green, sour, spicy, herbal, slightly fruity, animal, erogenic” on the left is (4R,4aS,6R,8aS)-(+)-tetrahydronootkatone and on the right its mirror image (4S,4aR,6S,8aR)-(−)-tetrahydronootkatone.