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Proc Natl Acad Sci U S A. 2015 May 26;112(21):E2766-74. doi: 10.1073/pnas.1503054112. Epub 2015 Apr 21.

Implausibility of the vibrational theory of olfaction.

Author information

  • 1Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222; eblock@albany.edu seogjoo.jang@qc.cuny.edu hiroaki.matsunami@duke.edu hanyizhuang@sjtu.edu.cn.
  • 2Department of Chemistry and Biochemistry, Queens College, and Graduate Center, City University of New York, Flushing, NY 11367; eblock@albany.edu seogjoo.jang@qc.cuny.edu hiroaki.matsunami@duke.edu hanyizhuang@sjtu.edu.cn.
  • 3Department of Molecular Genetics and Microbiology and Department of Neurobiology, Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC 27710; eblock@albany.edu seogjoo.jang@qc.cuny.edu hiroaki.matsunami@duke.edu hanyizhuang@sjtu.edu.cn.
  • 4Department of Chemistry, Yale University, New Haven, CT 06520;
  • 5Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;
  • 6Department of Chemistry, Yale University, New Haven, CT 06520; Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973;
  • 7Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; and.
  • 8Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; and Institute of Health Sciences, Shanghai Jiao tong University School of Medicine/Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai 200031, China eblock@albany.edu seogjoo.jang@qc.cuny.edu hiroaki.matsunami@duke.edu hanyizhuang@sjtu.edu.cn.

Abstract

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-recognizing receptor, MOR244-3, as well as other selected human and mouse ORs, responded similarly to normal, deuterated, and (13)C 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- to 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 odorants could be easily suppressed by quantum effects of nonodorant molecular vibrational modes. These and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.

KEYWORDS:

cyclopentadecanone; electron transfer; isotopomers; muscone; olfaction

PMID:
25901328
[PubMed - indexed for MEDLINE]
PMCID:
PMC4450420
Free PMC Article
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