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Science is perception: what can our sense of smell tell us about ourselves and the world around us?

Brookes JC - Philos Trans A Math Phys Eng Sci (2010)

Bottom Line: These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that ... smells.Most importantly, I draw links and comparisons as to how better understanding of how small (10's of atoms) molecules can interact so specially with large (10,000's of atoms) proteins in a way that is so integral to healthy living.Repercussions of this work are not just important in understanding a basic scientific tool used by us all, but often taken for granted, it is also a step closer to understanding generic mechanisms between drug and receptor, for example.

View Article: PubMed Central - PubMed

Affiliation: The London Centre for Nanotechnology, University College London, Gower Street, London WC1E 6BT, UK. ucapjcb@ucl.ac.uk

ABSTRACT
Human sensory processes are well understood: hearing, seeing, perhaps even tasting and touch--but we do not understand smell--the elusive sense. That is, for the others we know what stimuli causes what response, and why and how. These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that ... smells. I report, here, the status quo theories for olfaction, highlighting what we do not know, and explaining why dismissing the perception of the input as 'too subjective' acts as a roadblock not conducive to scientific inquiry. I outline the current and new theory that conjectures a mechanism for signal transduction based on quantum mechanical phenomena, dubbed the 'swipe card', which is perhaps controversial but feasible. I show that such lines of thinking may answer some questions, or at least pose the right questions. Most importantly, I draw links and comparisons as to how better understanding of how small (10's of atoms) molecules can interact so specially with large (10,000's of atoms) proteins in a way that is so integral to healthy living. Repercussions of this work are not just important in understanding a basic scientific tool used by us all, but often taken for granted, it is also a step closer to understanding generic mechanisms between drug and receptor, for example.

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Related in: MedlinePlus

(a) (4R)-(−)-carvone with the isopropenyl group axial to the ring. (b) (4R)-(−)-carvone with the isopropenyl group equatorial to the ring; adapted from Brookes et al. (2009). (c) The ‘twist’ , ‘boat’ and ‘chair’ states (and deviations inbetween) in cyclohexane; adapted from Juaristi (1995). Also, the difference (or lack of) between two-dimensional structures of (d) 5α-diH- and (e) 5β-diH-progesterone is shown.
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RSTA20100117F4: (a) (4R)-(−)-carvone with the isopropenyl group axial to the ring. (b) (4R)-(−)-carvone with the isopropenyl group equatorial to the ring; adapted from Brookes et al. (2009). (c) The ‘twist’ , ‘boat’ and ‘chair’ states (and deviations inbetween) in cyclohexane; adapted from Juaristi (1995). Also, the difference (or lack of) between two-dimensional structures of (d) 5α-diH- and (e) 5β-diH-progesterone is shown.

Mentions: Mirror image molecules are of interest because they exemplify the importance of shape in receptor detection, while still leaving the rules of shape selectivity obscure. They clearly show that the positions of atoms matter, though we still lack a scientific explanation as to why. A recent study by Brookes et al. (2009), which categorizes a suite of mirror image molecules documented by Leffingwell and associates, finds that, by categorizing the odorants by their scent descriptors and physical attributes, a simple rule can be determined. The rule is that odorant molecules of an enantiomer pair will smell alike (type 1) when they are rigid, and will smell different (type 2) when they are flexible (Brookes et al. 2009). This study of flexibility determined that those odorant molecules containing six-membered rings can twist and pseudo-rotate between ‘twist’-, ‘boat’- and ‘chair’-like configurations, similar to the flexibility seen in cylcohexane (figure 4), or have cis–trans stereo-isomeric flexibilities. This begs the question: which structure is it that is recognized by the receptor? It is perhaps more relevant to ask which shape turns the receptor ‘on’ as opposed to which shape allows the odorant (ligand) to get there. Note that the degree of flexibility will affect recognition at the site (affinity) but also the signalling or switching (efficacy/actuation). I propose that the evidence of differentiable mirror image odorants determines the importance of flexibility in olfactory actuation. It is common in the relevant literature these days to propose that flexibility aids the affinity a ligand has for a receptor site. This would imply, however, that two mirror image related molecules, equal in degrees of flexibility, would activate an equal set of receptors and smell the same, when they often do not. The inference that greater flexibility determines a more promiscuous ligand is not valid here. Flexibility could be as much a hindrance as an aid when it comes to ligand–receptor actuation.


Science is perception: what can our sense of smell tell us about ourselves and the world around us?

Brookes JC - Philos Trans A Math Phys Eng Sci (2010)

(a) (4R)-(−)-carvone with the isopropenyl group axial to the ring. (b) (4R)-(−)-carvone with the isopropenyl group equatorial to the ring; adapted from Brookes et al. (2009). (c) The ‘twist’ , ‘boat’ and ‘chair’ states (and deviations inbetween) in cyclohexane; adapted from Juaristi (1995). Also, the difference (or lack of) between two-dimensional structures of (d) 5α-diH- and (e) 5β-diH-progesterone is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2944383&req=5

RSTA20100117F4: (a) (4R)-(−)-carvone with the isopropenyl group axial to the ring. (b) (4R)-(−)-carvone with the isopropenyl group equatorial to the ring; adapted from Brookes et al. (2009). (c) The ‘twist’ , ‘boat’ and ‘chair’ states (and deviations inbetween) in cyclohexane; adapted from Juaristi (1995). Also, the difference (or lack of) between two-dimensional structures of (d) 5α-diH- and (e) 5β-diH-progesterone is shown.
Mentions: Mirror image molecules are of interest because they exemplify the importance of shape in receptor detection, while still leaving the rules of shape selectivity obscure. They clearly show that the positions of atoms matter, though we still lack a scientific explanation as to why. A recent study by Brookes et al. (2009), which categorizes a suite of mirror image molecules documented by Leffingwell and associates, finds that, by categorizing the odorants by their scent descriptors and physical attributes, a simple rule can be determined. The rule is that odorant molecules of an enantiomer pair will smell alike (type 1) when they are rigid, and will smell different (type 2) when they are flexible (Brookes et al. 2009). This study of flexibility determined that those odorant molecules containing six-membered rings can twist and pseudo-rotate between ‘twist’-, ‘boat’- and ‘chair’-like configurations, similar to the flexibility seen in cylcohexane (figure 4), or have cis–trans stereo-isomeric flexibilities. This begs the question: which structure is it that is recognized by the receptor? It is perhaps more relevant to ask which shape turns the receptor ‘on’ as opposed to which shape allows the odorant (ligand) to get there. Note that the degree of flexibility will affect recognition at the site (affinity) but also the signalling or switching (efficacy/actuation). I propose that the evidence of differentiable mirror image odorants determines the importance of flexibility in olfactory actuation. It is common in the relevant literature these days to propose that flexibility aids the affinity a ligand has for a receptor site. This would imply, however, that two mirror image related molecules, equal in degrees of flexibility, would activate an equal set of receptors and smell the same, when they often do not. The inference that greater flexibility determines a more promiscuous ligand is not valid here. Flexibility could be as much a hindrance as an aid when it comes to ligand–receptor actuation.

Bottom Line: These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that ... smells.Most importantly, I draw links and comparisons as to how better understanding of how small (10's of atoms) molecules can interact so specially with large (10,000's of atoms) proteins in a way that is so integral to healthy living.Repercussions of this work are not just important in understanding a basic scientific tool used by us all, but often taken for granted, it is also a step closer to understanding generic mechanisms between drug and receptor, for example.

View Article: PubMed Central - PubMed

Affiliation: The London Centre for Nanotechnology, University College London, Gower Street, London WC1E 6BT, UK. ucapjcb@ucl.ac.uk

ABSTRACT
Human sensory processes are well understood: hearing, seeing, perhaps even tasting and touch--but we do not understand smell--the elusive sense. That is, for the others we know what stimuli causes what response, and why and how. These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that ... smells. I report, here, the status quo theories for olfaction, highlighting what we do not know, and explaining why dismissing the perception of the input as 'too subjective' acts as a roadblock not conducive to scientific inquiry. I outline the current and new theory that conjectures a mechanism for signal transduction based on quantum mechanical phenomena, dubbed the 'swipe card', which is perhaps controversial but feasible. I show that such lines of thinking may answer some questions, or at least pose the right questions. Most importantly, I draw links and comparisons as to how better understanding of how small (10's of atoms) molecules can interact so specially with large (10,000's of atoms) proteins in a way that is so integral to healthy living. Repercussions of this work are not just important in understanding a basic scientific tool used by us all, but often taken for granted, it is also a step closer to understanding generic mechanisms between drug and receptor, for example.

Show MeSH
Related in: MedlinePlus