Taste and chirality: L-glucose sweetness is mediated by TAS1R2/TAS2R3 receptor

Nitzan Dubovski, Yaron Ben Shoshan-Galeczki, Einav Malach, Masha Y. Niv*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Naturally occurring sugars usually have D-chirality. While a change in chirality typically affects ligand–receptor interaction, non-caloric L-glucose was reported as sweet for humans. Here we show that L- and D-glucose have similar sensory detection thresholds (0.041 ± 0.006 M for D-glucose, and 0.032 ± 0.007 M for L-glucose) and similar sweetness intensities at suprathreshold concentrations. We demonstrate that L-glucose acts via the sweet taste receptor TAS1R2/TAS1R3, eliciting a dose-dependent activation in cell-based functional assays. Computational docking of glucose to the VFT domain of TAS1R2 suggests two sub-pockets, each compatible with each of the enantiomers. While some polar residues (Y103, D142, N143, S144, Y215) are unique for sub-pocket A and others (D307, T326, E382, R383) for sub-pocket B, no interaction is unique for only one enantiomer. The many options for creating hydrogen bonds with the hydroxyl moieties of glucose explain how both enantiomers can fit each one of the sub-pockets.

Original languageAmerican English
Article number131393
JournalFood Chemistry
StatePublished - 30 Mar 2022

Bibliographical note

Funding Information:
The study was supported by ISF grant #1129/19 and UHJ-France and the Foundation Scopus.

Funding Information:
The authors thank Mr. Tomer Green for help with sensory detection threshold experiments and for critical reading of the manuscript, Dr. Tsafi Danieli for help and advice with the cell-culture and transfection. We thank Dr. R. F. Margolskee for the pcDNA3 of chimeric G?16gust44 and Dr. Maik Behrens for the pcDNA3 of TAS1R3, and for the pcDNA5FRT PM of TAS1R2. Nitzan Dubovski is a recipient of the Robert H. Smith Fellowship for Excellence in Agriculture, Food and Environment. Masha Niv is a member of COST action ERNEST (CA18133). The study was supported by ISF grant #1129/19 and UHJ-France and the Foundation Scopus.

Publisher Copyright:
© 2021 Elsevier Ltd

Copyright © 2021 Elsevier Ltd. All rights reserved.


  • Enantiomer
  • GPCR
  • Stereospecificity
  • Sugar
  • Sweet
  • Taste
  • Receptors, G-Protein-Coupled/genetics
  • Hydrogen Bonding
  • Humans
  • Glucose
  • Sugars


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