title: The Odorant ( R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46.
abstract: Sensory studies showed the volatile fraction of lemon grass and its main constituent, the odor-active citronellal, to significantly decrease the perceived bitterness of a black tea infusion as well as caffeine solutions. Seven citronellal-related derivatives were synthesized and shown to inhibit the perceived bitterness of caffeine in a structure-dependent manner. The aldehyde function at carbon 1, the ( R)-configuration of the methyl-branched carbon 3, and a hydrophobic carbon chain were found to favor the bitter inhibitory activity of citronellal; for example, even low concentrations of 25 ppm were observed to reduce bitterness perception of caffeine solution (6 mmol/L) by 32%, whereas ( R)-citronellic acid (100 pm) showed a reduction of only 21% and ( R)-citronellol (100 pm) was completely inactive. Cell-based functional experiments, conducted with the human bitter taste receptors TAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46 reported to be sensitive to caffeine, revealed ( R)-citronellal to completely block caffeine-induced calcium signals in TAS2R43-expressing cells, and, to a lesser extent, in TAS2R46-expressing cells. Stimulation of TAS2R43-expressing cells with structurally different bitter agonists identified ( R)-citronellal as a general allosteric inhibitor of TAS2R43. Further structure/activity studies indicated 3-methyl-branched aliphatic aldehydes with a carbon chain of ≥4 C atoms as best TAS2R43 antagonists. Whereas odor-taste interactions have been mainly interpreted in the literature to be caused by a central neuronal integration of odors and tastes, rather than by peripheral events at the level of reception, the findings of this study open up a new dimension regarding the interaction of the two chemical senses.
authors: Chair of Food Chemistry and Molecular Sensory Science , Technische Universität München , Lise-Meitner-Straße 34 , D-85354 Freising-Weihenstephan , Germany.
authors: Barbara
authors: B
authors: Suess
authors: Department of Molecular Genetics , German Institute of Human Nutrition (DIFE) Potsdam-Rehbrücke , Arthur-Scheunert-Allee 114-116 , 14558 Nuthetal , Germany.
authors: Anne
authors: A
authors: Brockhoff
authors: Department of Molecular Genetics , German Institute of Human Nutrition (DIFE) Potsdam-Rehbrücke , Arthur-Scheunert-Allee 114-116 , 14558 Nuthetal , Germany.
authors: Wolfgang
authors: W
authors: Meyerhof
authors: Chair of Food Chemistry and Molecular Sensory Science , Technische Universität München , Lise-Meitner-Straße 34 , D-85354 Freising-Weihenstephan , Germany.
authors: Thomas
authors: T
authors: Hofmann
mesh_terms: D000080462:Acyclic Monoterpenes; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism*; D006801:Humans; D039821:Monoterpenes / Q000737:chemistry / Q000378:metabolism*; D009812:Odorants / Q000032:analysis*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013649:Taste; D000098706:Taste Receptors, Type 2
chemical_list: D000080462:Acyclic Monoterpenes; D000447:Aldehydes; D039821:Monoterpenes; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D002110:Caffeine; C108217:citronellal
keywords: TAS2R; bitterness inhibition; caffeine; citronellal; monoterpenes; taste modulation