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Title: Implausibility of the vibrational theory of olfaction

The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of these compounds in vitro. Furthermore, the mouse (methylthio)methanethiol (MTMT)-recognizing receptor, MOR244-3, and other selected human and mouse ORs, responded similarly to normal, deuterated, and ¹³C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d₃₀ lacks the 1,380-1,550 cm⁻¹ IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorantsmore » could be easily suppressed by quantum effects of non-odorant molecular vibrational modes. As a result, these and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [1] ;  [1] ;  [6] ;  [6] ;  [6] ;  [1] ;  [5] ;  [6] ;  [1] ;  [5] ;  [7]
  1. Univ. at Albany, State Univ. of New York, Albany, NY (United States)
  2. Yale Univ., New Haven, CT (United States); Brookhaven National Lab. (BNL), Upton, NY (United States)
  3. City Univ. of New York, Flushing, NY (United States)
  4. Duke Univ. Medical Center, Durham, NC (United States)
  5. Yale Univ., New Haven, CT (United States)
  6. Shanghai Jiaotong Univ. School of Medicine, Shanghai (China)
  7. Shanghai Jiaotong Univ. School of Medicine, Shanghai (China); Shanghai Jiao tong Univ. School of Medicine/Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai (China)
Publication Date:
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 0027-8424
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 112; Journal Issue: 21; Journal ID: ISSN 0027-8424
National Academy of Sciences, Washington, DC (United States)
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; olfaction; isotopomers; cyclopentadecanone; muscone; electron transfer