Shape theory of olfaction
Encyclopedia
The Shape theory of smell
states that a molecule's particular smell is due to a 'lock and key' mechanism by which a scent molecule
fits into olfactory receptor
s in the nasal
epithelium
.
's notion of shape-based molecular interactions to propose a shape-based theory of odor. This superseded the older vibration theory of olfaction
and remains the mainstream theory, in both commercial fragrance chemistry and academic molecular biology. Three years after Moncrieff proposed the theory, John Amoore speculated further that the over ten thousand smells distinguishable by the human olfaction system resulted from the combination of seven basic primary odors correlating to odor receptors for each, much as the spectrum of perceived colors in visible light is generated by the activation of three primary color receptors. Amoore's seven primary odors included sweaty, spermous, fishy, malty, urinous and musky. His most convincing work was done on the camphoraceous odor, for which he posited a hemispherical socket in which spherical molecules, such as camphor
, cyclooctane
, and naphthalene
could bind.
When Linda Buck and Richard Axel
published their Nobel Prize
winning research on the olfactory receptors in 1991, they identified in mice 1,000 G-protein-coupled receptors used for olfaction. Since all types of G-protein receptors currently known are activated through binding of molecules with highly specific conformations, or shape, it is assumed that olfactory receptors operate in a similar fashion. Further research on human olfaction systems identified 347 olfactory receptors.
The most recent shape theory, also known as odotope theory
or Weak Shape Theory, holds that a combination of activated receptors is responsible for any one smell, as opposed to the older model of one receptor, one shape, one smell. Receptors in the odotope model recognize only small structural features on each molecule, and the brain is responsible for processing the combined signal into an interpreted smell. Much current work on shape theory focuses on neural processing, rather than the specific interaction between odorant and receptor that generates the original signal http://www.hhmi.org/research/nobel/buck.html.
A study by Leslie B. Vosshall
and Andreas Keller, published in Nature Neuroscience
in 2004, tested several key predictions of the competing vibration theory and found no experimental support for it. The data were described by Vosshall as "consistent with the shape theory," although she added that "they don't prove the shape theory."
Olfaction
Olfaction is the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates...
states that a molecule's particular smell is due to a 'lock and key' mechanism by which a scent molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
fits into olfactory receptor
Olfactory receptor
Olfactory receptors expressed in the cell membranes of olfactory receptor neurons are responsible for the detection of odor molecules. Activated olfactory receptors are the initial player in a signal transduction cascade which ultimately produces a nerve impulse which is transmitted to the brain...
s in the nasal
Human nose
The visible part of the human nose is the protruding part of the face that bears the nostrils. The shape of the nose is determined by the ethmoid bone and the nasal septum, which consists mostly of cartilage and which separates the nostrils...
epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
.
History
In 1949, R.W. Moncrieff published an article in American Perfumer called "What is odor: a new theory," which used Linus PaulingLinus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
's notion of shape-based molecular interactions to propose a shape-based theory of odor. This superseded the older vibration theory of olfaction
Vibration theory of olfaction
The Vibration theory of smell proposes that a molecule's smell character is due to its vibrational frequency in the infrared range. The theory is opposed to the more widely accepted shape theory of olfaction, which proposes that a molecule's smell character is due to its shape.-Introduction:The...
and remains the mainstream theory, in both commercial fragrance chemistry and academic molecular biology. Three years after Moncrieff proposed the theory, John Amoore speculated further that the over ten thousand smells distinguishable by the human olfaction system resulted from the combination of seven basic primary odors correlating to odor receptors for each, much as the spectrum of perceived colors in visible light is generated by the activation of three primary color receptors. Amoore's seven primary odors included sweaty, spermous, fishy, malty, urinous and musky. His most convincing work was done on the camphoraceous odor, for which he posited a hemispherical socket in which spherical molecules, such as camphor
Camphor
Camphor is a waxy, white or transparent solid with a strong, aromatic odor. It is a terpenoid with the chemical formula C10H16O. It is found in wood of the camphor laurel , a large evergreen tree found in Asia and also of Dryobalanops aromatica, a giant of the Bornean forests...
, cyclooctane
Cyclooctane
Cyclooctane is a cycloalkane with the molecular formula 8. It is a simple colourless hydrocarbon, but it is often a reference compound for saturated eight-membered ring compounds in general.- Conformation :...
, and naphthalene
Naphthalene
Naphthalene is an organic compound with formula . It is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08 ppm by mass. As an aromatic hydrocarbon, naphthalene's structure consists of a fused pair of benzene rings...
could bind.
When Linda Buck and Richard Axel
Richard Axel
Richard Axel is an American neuroscientist whose work on the olfactory system won him and Linda B. Buck, a former post-doctoral scientist in his research group, the Nobel Prize in Physiology or Medicine in 2004....
published their Nobel Prize
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
winning research on the olfactory receptors in 1991, they identified in mice 1,000 G-protein-coupled receptors used for olfaction. Since all types of G-protein receptors currently known are activated through binding of molecules with highly specific conformations, or shape, it is assumed that olfactory receptors operate in a similar fashion. Further research on human olfaction systems identified 347 olfactory receptors.
The most recent shape theory, also known as odotope theory
Odotope theory
Odotope theory, also known as weak shape theory, is a theory of how olfactory receptors bind to odor molecules. The theory proposes that a combination of shape factors determine the coupling. The word itself is an analogy to epitopes.- References :...
or Weak Shape Theory, holds that a combination of activated receptors is responsible for any one smell, as opposed to the older model of one receptor, one shape, one smell. Receptors in the odotope model recognize only small structural features on each molecule, and the brain is responsible for processing the combined signal into an interpreted smell. Much current work on shape theory focuses on neural processing, rather than the specific interaction between odorant and receptor that generates the original signal http://www.hhmi.org/research/nobel/buck.html.
Support
Numerous studies have been conducted to elucidate the complex relationship between the shape of an odorous molecule and its perceived smell character, and fragrance chemists have proposed structure models for the smells of amber, sandalwood, and camphor, among others.A study by Leslie B. Vosshall
Leslie B. Vosshall
-Biography:Leslie Birgit Vosshall, Ph.D., is an American neurobiologist who is well known for her contributions in the field of olfaction, particularly for the discovery and subsequent characterization of the insect olfactory receptor family. She received her Ph.D...
and Andreas Keller, published in Nature Neuroscience
Nature Neuroscience
Nature Neuroscience is a monthly scientific journal published by Nature Publishing Group. Its focus is original research papers relating specifically to neuroscience and was established in May 1998. According to the Journal Citation Reports, Nature Neuroscience has a 2009 impact factor of 14.345,...
in 2004, tested several key predictions of the competing vibration theory and found no experimental support for it. The data were described by Vosshall as "consistent with the shape theory," although she added that "they don't prove the shape theory."
Challenges
- Despite numerous studies, shape theory has yet to discover shape-odor relations with great predictive power. http://www3.interscience.wiley.com/cgi-bin/abstract/113314071/ABSTRACT?CRETRY=1&SRETRY=0.
- Similarly shaped molecules with different molecular vibrations have different smells (metalloceneMetalloceneA metallocene is a compound typically consisting of two cyclopentadienyl anions bound to a metal center in the oxidation state II, with the resulting general formula 2M. Closely related to the metallocenes are the metallocene derivatives, e.g. titanocene dichloride, vanadocene dichloride...
experiment and deuteriumDeuteriumDeuterium, also called heavy hydrogen, is one of two stable isotopes of hydrogen. It has a natural abundance in Earth's oceans of about one atom in of hydrogen . Deuterium accounts for approximately 0.0156% of all naturally occurring hydrogen in Earth's oceans, while the most common isotope ...
replacement of molecular hydrogenHydrogenHydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
). - Differently shaped molecules with similar molecular vibrations have similar smells (replacement of carbonCarbonCarbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
double bonds by sulfurSulfurSulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
atoms and the disparate shaped amber odorants). - Hiding functional groupFunctional groupIn organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
s does not hide the group's characteristic odor. - Very small molecules of similar shape, which seem most likely to be confused by a shape-based system, have extremely distinctive odors, such as hydrogen sulfideHydrogen sulfideHydrogen sulfide is the chemical compound with the formula . It is a colorless, very poisonous, flammable gas with the characteristic foul odor of expired eggs perceptible at concentrations as low as 0.00047 parts per million...
. - Some studies seem to show that human beings and animals can distinguish between isotopes by smell, despite their identical shapes http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6R-42G0KG3-B&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ee322cf64e5ae26015b2c5bf70b9f492http://flexitral.com/research/Meloan_1995.pdf.
- Odor descriptions in the olfaction literature correlate more strongly with their vibrational frequencies than with their molecular shape http://www.rsc.org/Publishing/Journals/OB/article.asp?doi=B409802A.