Abstract
Background Gymnemic acids, triterpene glycosides, are known to act as human-specific sweet inhibitors. The long-lasting effect of gymnemic acids is diminished by γ-cyclodextrin. Here, we focus on the molecular mechanisms underlying the interaction between gymnemic acids and sweet taste receptor and/or γ-cyclodextrin by a sweet taste receptor assay in transiently transfected HEK293 cells. Highlight Application of gymnemic acids inhibited intracellular calcium responses to sweet compounds in HEK293 cells expressing human TAS1R2+TAS1R3 but not in those expressing the mouse sweet receptor Tas1r2+Tas1r3 after application of gymnemic acids. The effect of gymnemic acids was reduced after rinsing cells with γ-cyclodextrin. Based on species-specific sensitivities to gymnemic acids, we showed that the transmembrane domain of hTAS1R3 is involved in the sensitivity to gymnemic acids. Point mutation analysis in the transmembrane domain of hTAS1R3 revealed that gymnemic acids shared the same binding pocket with another sweet inhibitor, lactisole. Sensitivity to sweet compounds was also reduced by mixtures of glucuronic acid, a common gymnemic acid. In our molecular models, gymnemic acids interacted with a binding site formed in the transmembrane domain of hTAS1R3. Conclusion Gymnemic acids inhibit sweet responses in humans through an interaction between the glucuronosyl group of gymnemic acids and the transmembrane domain of hTAS1R3. Our molecular model provides a foundation for the development of taste modifiers.
| Original language | English |
|---|---|
| Pages (from-to) | 127-130 |
| Number of pages | 4 |
| Journal | journal of oral biosciences |
| Volume | 59 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Aug 1 2017 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Dentistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Binding properties between human sweet receptor and sweet-inhibitor, gymnemic acids. / Sanematsu, Keisuke; Shigemura, Noriatsu; Ninomiya, Yuzo.
In: journal of oral biosciences, Vol. 59, No. 3, 01.08.2017, p. 127-130.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Binding properties between human sweet receptor and sweet-inhibitor, gymnemic acids
AU - Sanematsu, Keisuke
AU - Shigemura, Noriatsu
AU - Ninomiya, Yuzo
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Background Gymnemic acids, triterpene glycosides, are known to act as human-specific sweet inhibitors. The long-lasting effect of gymnemic acids is diminished by γ-cyclodextrin. Here, we focus on the molecular mechanisms underlying the interaction between gymnemic acids and sweet taste receptor and/or γ-cyclodextrin by a sweet taste receptor assay in transiently transfected HEK293 cells. Highlight Application of gymnemic acids inhibited intracellular calcium responses to sweet compounds in HEK293 cells expressing human TAS1R2+TAS1R3 but not in those expressing the mouse sweet receptor Tas1r2+Tas1r3 after application of gymnemic acids. The effect of gymnemic acids was reduced after rinsing cells with γ-cyclodextrin. Based on species-specific sensitivities to gymnemic acids, we showed that the transmembrane domain of hTAS1R3 is involved in the sensitivity to gymnemic acids. Point mutation analysis in the transmembrane domain of hTAS1R3 revealed that gymnemic acids shared the same binding pocket with another sweet inhibitor, lactisole. Sensitivity to sweet compounds was also reduced by mixtures of glucuronic acid, a common gymnemic acid. In our molecular models, gymnemic acids interacted with a binding site formed in the transmembrane domain of hTAS1R3. Conclusion Gymnemic acids inhibit sweet responses in humans through an interaction between the glucuronosyl group of gymnemic acids and the transmembrane domain of hTAS1R3. Our molecular model provides a foundation for the development of taste modifiers.
AB - Background Gymnemic acids, triterpene glycosides, are known to act as human-specific sweet inhibitors. The long-lasting effect of gymnemic acids is diminished by γ-cyclodextrin. Here, we focus on the molecular mechanisms underlying the interaction between gymnemic acids and sweet taste receptor and/or γ-cyclodextrin by a sweet taste receptor assay in transiently transfected HEK293 cells. Highlight Application of gymnemic acids inhibited intracellular calcium responses to sweet compounds in HEK293 cells expressing human TAS1R2+TAS1R3 but not in those expressing the mouse sweet receptor Tas1r2+Tas1r3 after application of gymnemic acids. The effect of gymnemic acids was reduced after rinsing cells with γ-cyclodextrin. Based on species-specific sensitivities to gymnemic acids, we showed that the transmembrane domain of hTAS1R3 is involved in the sensitivity to gymnemic acids. Point mutation analysis in the transmembrane domain of hTAS1R3 revealed that gymnemic acids shared the same binding pocket with another sweet inhibitor, lactisole. Sensitivity to sweet compounds was also reduced by mixtures of glucuronic acid, a common gymnemic acid. In our molecular models, gymnemic acids interacted with a binding site formed in the transmembrane domain of hTAS1R3. Conclusion Gymnemic acids inhibit sweet responses in humans through an interaction between the glucuronosyl group of gymnemic acids and the transmembrane domain of hTAS1R3. Our molecular model provides a foundation for the development of taste modifiers.
UR - http://www.scopus.com/inward/record.url?scp=85020789362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020789362&partnerID=8YFLogxK
U2 - 10.1016/j.job.2017.05.004
DO - 10.1016/j.job.2017.05.004
M3 - Review article
VL - 59
SP - 127
EP - 130
JO - Journal of Oral Biosciences
JF - Journal of Oral Biosciences
SN - 1349-0079
IS - 3
ER -