The Odorant (R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46

Journal of Agricultural and Food Chemistry

Volumn 66, Issue 10, 2018, Pages 2301-2311

  Suess, Barbara ^a   Brockhoff, Anne ^b   Meyerhof, Wolfgang ^b   Hofmann, Thomas ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b GERMAN INSTITUTE OF HUMAN NUTRITION   (Germany)

Author keywords

bitterness inhibition; caffeine; citronellal; monoterpenes; TAS2R; taste modulation

Indexed keywords

ALDEHYDES; CELLS; CHAINS; CYTOLOGY; MONOTERPENES; ODORS;

ALIPHATIC ALDEHYDES; ALLOSTERIC INHIBITOR; CITRONELLAL; INHIBITORY ACTIVITY; LOW CONCENTRATIONS; STRUCTURE DEPENDENT; TAS2R; VOLATILE FRACTIONS;

CAFFEINE;

ALDEHYDE; CAFFEINE; CITRONELLAL; FRAGRANCE; G PROTEIN COUPLED RECEPTOR; TASTE RECEPTORS, TYPE 2; TERPENE;

CHEMISTRY; GENETICS; HUMAN; METABOLISM; TASTE;

ALDEHYDES; CAFFEINE; HUMANS; MONOTERPENES; ODORANTS; RECEPTORS, G-PROTEIN-COUPLED; TASTE;

EID: 85043773358     PISSN: 00218561     EISSN: 15205118     Source Type: Journal    
DOI: 10.1021/acs.jafc.6b03554     Document Type: Article

References (48)

1. Behrens, M.; Meyerhof, W.; Hellfritsch, C.; Hofmann, T. Sweet and umami taste: natural products, their chemosensory targets, and beyond. Angew. Chem., Int. Ed. 2011, 50, 2220-2242, 10.1002/anie.201002094
2. Meyerhof, W.; Batram, C.; Kuhn, C.; Brockhoff, A.; Chudoba, E.; Bufe, B.; Appendino, G.; Behrens, M. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem. Senses 2010, 35, 157-170, 10.1093/chemse/bjp092
3. Meyerhof, W.; Born, S.; Brockhoff, A.; Behrens, M. Molecular biology of mammalian bitter taste receptors. A review. Flavour Fragrance J. 2011, 26, 260-268, 10.1002/ffj.2041
4. Behrens, M. The human taste receptor hTAS2R14 responds to a variety of different bitter compounds. Biochem. Biophys. Res. Commun. 2004, 319, 479-485, 10.1016/j.bbrc.2004.05.019
5. Born, S.; Levit, A.; Niv, M. Y.; Meyerhof, W.; Behrens, M. The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands. J. Neurosci. 2013, 33, 201-213, 10.1523/JNEUROSCI.3248-12.2013
6. Brockhoff, A.; Behrens, M.; Massarotti, A.; Appendino, G.; Meyerhof, W. Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. J. Agric. Food Chem. 2007, 55, 6236-6243, 10.1021/jf070503p
7. Behrens, M.; Foerster, S.; Staehler, F.; Raguse, J. D.; Meyerhof, W. Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells. J. Neurosci. 2007, 27, 12630-12640, 10.1523/JNEUROSCI.1168-07.2007
8. Behrens, M.; Brockhoff, A.; Batram, C.; Kuhn, C.; Appendino, G.; Meyerhof, W. The human bitter taste receptor hTAS2R50 is activated by the two natural bitter terpenoids andrographolide and amarogentin. J. Agric. Food Chem. 2009, 57, 9860-9866, 10.1021/jf9014334
9. Thalmann, S.; Behrens, M.; Meyerhof, W. Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol. Biochem. Biophys. Res. Commun. 2013, 435, 267-273, 10.1016/j.bbrc.2013.04.066
10. Roland, W. S.; van Buren, L.; Gruppen, H.; Driesse, M.; Gouka, R. J.; Smit, G.; Vincken, J. P. Bitter taste receptor activation by flavonoids and isoflavonoids: modeled structural requirements for activation of hTAS2R14 and hTAS2R39. J. Agric. Food Chem. 2013, 61, 10454-10466, 10.1021/jf403387p
11. Bufe, B.; Breslin, P. A.; Kuhn, C.; Reed, D. R.; Tharp, C. D.; Slack, J. P.; Kim, U. K.; Drayna, D.; Meyerhof, W. The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr. Biol. 2005, 15, 322-327, 10.1016/j.cub.2005.01.047
12. Bufe, B.; Hofmann, T.; Krautwurst, D.; Raguse, J. D.; Meyerhof, W. The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides. Nat. Genet. 2002, 32, 397-401, 10.1038/ng1014
13. Behrens, M.; Meyerhof, W. Bitter taste receptor research comes of age: from characterization to modulation of TAS2Rs. Semin. Cell Dev. Biol. 2013, 24, 215-221, 10.1016/j.semcdb.2012.08.006
14. Ley, J. P.; Blings, M.; Paetz, S.; Krammer, G. E.; Bertram, H.-J. New bitter-masking compounds: hydroxylated benzoic acid amides of aromatic amines as structural analogues of homoeriodictyol. J. Agric. Food Chem. 2006, 54, 8574-8579, 10.1021/jf0617061
15. Ley, J. P.; Paetz, S.; Blings, M.; Hoffmann-Lücke, P.; Bertram, H.-J.; Krammer, G. E. Structural analogues of homoeriodictyol as flavor modifiers. Part III: short chain gingerdione derivatives. J. Agric. Food Chem. 2008, 56, 6656-6664, 10.1021/jf8006536
16. Guadagni, D. G.; Maier, V. P.; Turnbaugh, J. G. Effect of neodiosmin on threshold and bitterness of limonin in water and orange juice. J. Food Sci. 1976, 41, 681-684, 10.1111/j.1365-2621.1976.tb00697-41-3.x
17. Ley, J. P.; Krammer, G. E.; Reinders, G.; Gatfield, I. L.; Bertram, H.-J. Evaluation of bitter masking flavanones from Herba Santa (Eriodictyon californicum (H. & A.) Torr., Hydrophyllaceae. J. Agric. Food Chem. 2005, 53, 6061-6066, 10.1021/jf0505170
18. Ley, J. P.; Dessoy, M.; Paetz, S.; Blings, M.; Hoffmann-Lücke, P.; Reichelt, K. V.; Krammer, G. E.; Pienkny, S.; Brandt, W.; Wessjohann, L. Identification of enterodiol as a masker for caffeine bitterness by using a pharmacophore model based on structural analogues of homoeriodictyol. J. Agric. Food Chem. 2012, 60, 6303-6311, 10.1021/jf301335z
19. Soldo, T.; Blank, I.; Hofmann, T. (+)-(S)-Alapyridaine-a general taste enhancer?. Chem. Senses 2003, 28, 371-379, 10.1093/chemse/28.5.371
20. Soldo, T.; Hofmann, T. Application of hydrophilic interaction liquid chromatography/comparative taste dilution analysis for identification of a bitter inhibitor by a combinatorial approach based on Maillard reaction chemistry. J. Agric. Food Chem. 2005, 53, 9165-9171, 10.1021/jf051701o
21. Gravina, S. A.; McGregor, R. A.; Nossoughi, R.; Kherlopian, J.; Hofmann, T. Biomimetic in vitro assay for the characterization of bitter tastants and identification of bitter taste blockers. In Challenges in Taste Chemistry and Biology; Hofmann, T., Ho, C.-H., Pickenhagen, W., Eds.; ACS Symposium Series 867; American Chemical Society: Washington, DC, USA, 2003; 91-101.
22. Kuhn, C.; Bufe, B.; Winnig, M.; Hofmann, T.; Frank, O.; Behrens, M.; Lewtschenko, T.; Slack, J. P.; Ward, C. D.; Meyerhof, W. Bitter taste receptors for saccharin and acesulfame K. J. Neurosci. 2004, 24, 10260-10265, 10.1523/JNEUROSCI.1225-04.2004
23. Slack, J. P.; Brockhoff, A.; Batram, C.; Menzel, S.; Sonnabend, C.; Born, S.; Galindo, M. M.; Kohl, S.; Thalmann, S.; Ostopovici-Halip, L.; Simons, C. T.; Ungureanu, I.; Duineveld, K.; Bologa, C. G.; Behrens, M.; Furrer, S. M.; Oprea, T. I.; Meyerhof, W. Modulation of bitter taste perception by a small molecule hTAS2R antagonist. Curr. Biol. 2010, 20, 1104-1109, 10.1016/j.cub.2010.04.043
24. Brockhoff, A.; Behrens, M.; Roudnitzky, N.; Appendino, G.; Avonto, C.; Meyerhof, W. Receptor agonism and antagonism of dietary bitter compounds. J. Neurosci. 2011, 31, 14775-14782, 10.1523/JNEUROSCI.2923-11.2011
25. Roland, W. S. U.; Gouka, R. J.; Gruppen, H.; Driesse, M.; van Buren, L.; Smit, G.; Vincken, J.-P. 6-Methoxyflavanones as bitter taste receptor blockers for hTAS2R39. PLoS One 2014, 9, e94451, 10.1371/journal.pone.0094451
26. Fletcher, J. N.; Kinghorn, A. D.; Slack, J. P.; McCluskey, T. S.; Odley, A.; Jia, Z. In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31. J. Agric. Food Chem. 2011, 59, 13117-13121, 10.1021/jf204359q
27. Greene, T. A.; Alarcon, S.; Thomas, A.; Berdougo, E.; Doranz, B. J.; Breslin, P. A. S.; Rucker, J. B.; Matsunami, H. Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One 2011, 6, e20123, 10.1371/journal.pone.0020123
28. Pydi, S. P.; Jaggupilli, A.; Nelson, K. M.; Abrams, S. R.; Bhullar, R. P.; Loewen, M. C.; Chelikani, P. Abscisic acid acts as a blocker of the bitter taste G protein-coupled receptor T2R4. Biochemistry 2015, 54, 2622-2631, 10.1021/acs.biochem.5b00265
29. Pydi, S. P.; Sobotkiewicz, T.; Billakanti, R.; Bhullar, R. P.; Loewen, M. C.; Chelikani, P. Amino acid derivatives as bitter taste receptor (T2R) blockers. J. Biol. Chem. 2014, 289, 25054-25066, 10.1074/jbc.M114.576975
30. Green, B. G.; Nachtigal, D.; Hammond, S.; Lim, J. Enhancement of retronasal odors by taste. Chem. Senses 2012, 37, 77-86, 10.1093/chemse/bjr068
31. Engel, W.; Bahr, W.; Schieberle, P. Solvent assisted flavour evaporation (SAFE) new and versatile technique for the careful and direct isolation of aroma compounds from complex food matrices. Eur. Food Res. Technol. 1999, 209, 237-241, 10.1007/s002170050486
32. Yamaguchi, S.; Yoshikawa, T.; Ikeda, S.; Ninomiya, T. Measurement of the relative taste intensity of some l -α-amino acids and 5′-nucleotides. J. Food Sci. 1971, 36, 846-849, 10.1111/j.1365-2621.1971.tb15541.x
33. Festring, D.; Hofmann, T. Systematic studies on the chemical structure and umami enhancing activity of Maillard-modified guanosine 5′-monophosphates. J. Agric. Food Chem. 2011, 59, 665-676, 10.1021/jf103849e
34. Festring, D.; Brockhoff, A.; Meyerhof, W.; Hofmann, T. Stereoselective synthesis of amides sharing the guanosine 5′-monophosphate scaffold and umami enhancement studies using human sensory and hT1R1/rT1R3 receptor assays. J. Agric. Food Chem. 2011, 59, 8875-8885, 10.1021/jf202202h
35. 2-arylthiomethylation of guanosine 5′-monophosphates. J. Agric. Food Chem. 2014, 62, 11429-11440, 10.1021/jf504686s
36. Defrancq, E.; Leterme, A.; Pelloux, N.; L'homme, M.-F.; L'homme, J. Arylamidation de la guanosine par un agent cancérogène, le 2-aminofluorène. Approche intramoléculaire. Tetrahedron 1991, 47, 5725-5736, 10.1016/S0040-4020(01)86525-X
37. Dess, D. B.; Martin, J. C. A useful 12-I-5 triacetoxyperiodinane (the Dess-Martin periodinane) for the selective oxidation of primary or secondary alcohols and a variety of related 12-I-5 species. J. Am. Chem. Soc. 1991, 113, 7277-7287, 10.1021/ja00019a027
38. Zhu, J.; Ma, D. Total synthesis of microsclerodermin E. Angew. Chem., Int. Ed. 2003, 42, 5348-5351, 10.1002/anie.200352423
39. Ueda, T.; Ugawa, S.; Yamamura, H.; Imaizumi, Y.; Shimada, S. Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells. J. Neurosci. 2003, 23, 7376-7380
40. Schmidt, C. Influence of Proteins on the Tastants in Black Tea Infusions (in German). Dissertation, Technical University of Munich, 2012.
41. Stone, S. C.; Vasconcellos, F. A.; Lenarda o, E. J.; do Amaral, R. C.; Jacob, R. G.; Leivas Leite, F. P. Evaluation of potential use of Cymbopogon sp. essential oils, (R)-citronellal and N -citronellylamine in cancer chemotherapy. Int. J. Appl. Res. Nat. Prod. 2013, 6, 11-15
42. Brockhoff, A.; Behrens, M.; Niv, M. Y.; Meyerhof, W. Structural requirements of bitter taste receptor activation. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 11110-11115, 10.1073/pnas.0913862107
43. Christopoulos, A.; Kenakin, T. G protein-coupled receptor allosterism and complexing. Pharmacol. Rev. 2002, 54, 323-374, 10.1124/pr.54.2.323
44. Dunkel, A.; Steinhaus, M.; Kotthoff, M.; Nowak, B.; Krautwurst, D.; Schieberle, P.; Hofmann, T. Nature's chemical signatures in human olfaction: a foodborne perspective for future biotechnology. Angew. Chem., Int. Ed. 2014, 53, 7124-7143, 10.1002/anie.201309508
45. Frank, R. A.; Byram, J. Taste-smell interactions are tastant and odorant dependent. Chem. Senses 1988, 13, 445-455, 10.1093/chemse/13.3.445
46. Prescott, J.; Johnstone, V.; Francis, J. Odor-taste interactions: effects of attentional strategies during exposure. Chem. Senses 2004, 29, 331-340, 10.1093/chemse/bjh036
47. Schifferstein, H. N. J.; Verlegh, P. W. J. The role of congruency and pleasantness in odor-induced taste enhancement. Acta Psychol. 1996, 94, 87-105, 10.1016/0001-6918(95)00040-2
48. Stevenson, R. J.; Prescott, J.; Boakes, R. A. Confusing tastes and smells: how odours can influence the perception of sweet and sour tastes. Chem. Senses 1999, 24, 627-635, 10.1093/chemse/24.6.627