OR51E1 is a receptor for fatty acids with 3-10 carbon atoms, particularly those with cheesy or sweaty perceptual notes. But this receptor is also sensitive to methyl eugenol, methyl salicylate, and menthol, none of which smell cheesy or sweaty. Previously it was hypothesized on the PrimaryOdors website that OR51E1 must encode a milky quality, since it is plausible that the three aforementioned non-acid agonists might have a milky note to their perceived odors. This article shows that in fact these agonists’ aromas do incorporate a cheesy note.
A mixture of OR51E1 agonists was prepared, consisting of: 0.75g butyl butyryl lactate; 0.45g methyl eugenol; 0.15g racemic menthol, 3% in EtOH; and 0.05g methyl salicylate. This mixture was labeled “+51E1”. To an identical mixture was added 0.45g bourgeonal, 15% in EtOH; and 0.45g hydroxycitronellal. The latter two compounds are OR51E1 antagonists, and the second mixture, labeled “-51E1”, serves as a control. Since all ingredients of the +51E1 mixture are also present in the -51E1 mixture, no aroma notes should be present in the former and absent in the latter unless they are masked by the antagonists.
The -51E1 mixture was smelled first. It has a smooth, plasticky, milky, muguet character with a minty undertone. This was compared to the +51E1 mixture which lacks the muguet note but has a distinctive sour cheesy overtone like artificial cheddar flavor. Once trained by this experiment to recognize this note, the author was able to detect the same note in all of the agonists, including the minty smelling ones. It is strongest in the lactate, weaker in the two aromatics, and weakest in the menthol, yet it is unmistakably present in all four. Further, when two scent strips were prepared with each a drop of butyl butyryl lactate and one with a drop of each of the antagonists, the scent strip without the antagonists smelled cheesy and buttery while the strip with the antagonists smelled like milk.
It’s important to rule out other possible antagonisms besides the target receptor. Bourgeonal and hydroxycitronellal are also antagonists of OR2W1, of which methyl salicylate is a weak agonist. Bourgeonal is also an OR5K1 antagonist while methyl eugenol is an agonist. Both bourgeonal and hydroxycitronellal are antagonists of OR5P3, OR51I2, and OR51L1, though none of the compounds used are agonists of OR5P3 or OR51L1, and are unlikely to be agonists of OR51L1. The proportion of methyl salicylate in the +51E1 mixture would cause only a slight stimulation of OR2W1, though the substantial quantity of methyl eugenol does add significant OR5K1 stimulation to the mixture’s odor.
OR5K1 is sensitive to substituted pyrazines and correlates strongly with nutty, roasted, earthy, and leguminous aromas (even licorice), and this pyrazinic note is easy to recognize for anyone familiar with pyrazine odors.
OR2W1 correlates with a diverse array of aroma notes, including herbal, fatty, sweet, tart, banana, orange, fresh, rancid, etc. Its sensitivity to the gas leak foulants ethanethiol and tert-butyl mercaptan, combined with its identity as the only known receptor for these compounds that is not heavily correlated with a sulfurous note, implies that the gas leak smell minus the sulfurous quality would be a pure OR2W1 note. Rancid vegetable would be a good way to describe such an odor.
However, menthol and methyl eugenol are not OR2W1 agonists, yet they definitely evoke the cheesy note in a side by side comparison of the compounds with and without the antagonists. Menthol and methyl salicylate are not OR5K1 antagonists, yet they definitely evoke the cheesy note in a side by side comparison. Only OR51E1 has the property of responding to all the agonists and being suppressed by the antagonists.
The author concludes that OR51E1’s contribution to the perceptual quality of odors is a cheddary/sour/buttery note similar to the odor of powdered artificial cheese.