Identification of Odorant-Receptor Interactions by Global Mapping of the Human Odorome

Abstract

The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome.

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction

“…Some support for the contributions of genetic background comes from seeing that the controls for the PPND kindred, who were mutation-negative family members, cluster with PPND NMCs. Also, the apparent relationship between UPSIT odors having significant contributions to PC2 and nodes in the human odorome [52] supports the hypothesis that this separation may reflect differences in either the subjects’ odorant receptor repertoire and/or differential connectivity patterns among brain regions involved in olfaction. The influence of shared genetic background on phenotypes in kindreds with mutations causing neurodegenerative disease has been highlighted previously.…”

“…UPSIT odors contributing to PC2 seem related to a subset of nodes within the human odorome network [52]. The odors with appreciable positive loadings [ pizza (loading = 0.24), paint thinner (0.18), cheddar cheese (0.17) and natural gas (0.16)] seem related to the nodes odorless-cheese-sour and medicine-phenol-harsh .…”

“…Inconsistent patterns of odor identification may reflect variation in the spectrum, distribution and density of olfactory receptors coupled with variability in the functional activation of single receptors due to the unequal intensities of odorants presented in different tests of olfactory function, including the UPSIT and BSIT. Not only are odorants often composed of multiple chemical compounds, single odorant receptors respond to multiple chemical compounds and multiple odorant receptors are activated by single chemical odorants [52]. Given the “many-to-many” mapping of odorants to receptors, it would be useful to understand whether single-compound odorants have greater consistency or reliability than multiple-compound odorants, assuming that multiple-compound odorants target a broader array of receptor types.…”

“…Yet perceived odors, even those associated with single odorant molecules, are often described using multiple terms related to contextual memories, reflecting their perception as an “ensemble of components” [52]. They can be associated with specific experiences or objects through retrieving information from semantic memory.…”

Study of Structure Activity Relationship to Determine of Aroma Compound Characteristic through Molecular Docking Testing

“…Pada level molekuler, senyawa aroma dapat berinteraksi secara spesifik terhadap beberapa olfaktori reseptor (g) yang terikat pada membran fosfolipid sel saraf. Hubungan interaksi antara senyawa aroma dan area ikatan olfaktori reseptor yang melibatkan sifat psikokimia dari keduanya terdefinisikan sebagai aktivasi selektif suatu sel saraf [4]. Olfaktori reseptor (OR) termasuk ke dalam kelompok G-protein coupled receptor (GPCR) dan memiliki karakteristik struktur berpilin (helix) dengan tujuh transmembran [5].…”