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

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

doi:10.1016/j.foodchem.2021.131393

Cited by 14 publications

(15 citation statements)

References 63 publications

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“…Rreproducing our previous findings (Dubovski N, Y Ben Shoshan-Galeczki, et al, 2022), we show that both D- and L-glucose evoked activation of T1R2/T1R3 HEK293T cells in a dose response manner, also in the usage of the WT T1R2 (Figure 4). In order to determine the role of T1R2 and T1R3 in the activation by D- and L-glucose, we transformed partial transfections of either of the two components, along with Gα 16gus44 .…”

Section: Resultssupporting

confidence: 89%

“…In our previous study (Dubovski N, Y Ben Shoshan-Galeczki, et al, 2022) we used a T1R2 plasmid received from colleagues several years ago. Following recommendations from Smith et al (Smith NJ et al, 2021), we sequenced the plasmid and found that this is the original reference sequence (RefSeq) (NM_152232.1), and contains 4 SNPs compared to the updated release RefSeq of T1R2 (NM_152232.4, which we will refer to as wild type, WT).…”

Section: Resultsmentioning

confidence: 99%

“…However, it is not metabolized and hence considered as a non-caloric sugar (Levin GV et al, 1995). In our previous study, we have proved for the first time that L-glucose sweetness is mediated by T1R2/T1R3 (Dubovski N, Y Ben Shoshan-Galeczki, et al, 2022). Here we studied the contribution of each of the sweet receptor subunits, T1R2 and T1R3, in D- and L-glucose recognition, and evaluated the effects of SNPs found in the current vs original reference sequences of T1R2.…”

Section: Introductionmentioning

confidence: 93%

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Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers

Dubovski

Galezcki

Malach

et al. 2022

Preprint

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We have previously shown that L-glucose, the non-caloric enantiomer of D-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here we show that D- and L-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either L or D-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM_152232.1) is less sensitive by almost an order of magnitude than reference sequence at the time this study was performed (NM_152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in-vitro. It is important both for practical assay sensitivity, and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and of the partial transfections were similar for D and L enantiomers, their dose response curves remained distinct, with L-glucose reaching an early plateau.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

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Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers

Dubovski

Galezcki

Malach

et al. 2022

Preprint

Self Cite

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“…Both configurations bind to the same region of TAS1R2 and no point mutations have been identified which would affect one and not the other. Moreover, the subjective perception in sweet taste tests revealed no significant difference between the enantiomers (Dubovski et al, 2022). In silico simulations showed that sucrose has a binding site mediated by hydrogen bonds close to the D142 and E302 residues.…”

Section: Introductionmentioning

confidence: 93%

TAS1 receptors. An overview of their functions, expression and genetic variations

Opriță¹,

Babeș²,

Domocoș³

2022

Rev. Biol. Biomed. Sci.

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Heteromeric G protein-coupled receptors are essential in taste transduction, a characteristic important for vertebrates. Type 1 taste receptors mediate sweet and umami sensing via two heterodimers: TAS1R2/TAS1R2 and TAS1R1/TAS1R3. Evidently, these heterodimers are expressed in taste buds, but also in several other tissues like the gastrointestinal tract, bone, pancreas and bladder. Because of its role in transducing the sweet taste, there have been plenty of investigations regarding genetic variations associated with obesity or dental caries.

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“…Some people have hesitations toward “artificial” sweeteners, and although this is poorly grounded from a scientific viewpoint, there is a drive toward finding “natural” low-calorie sweeteners. l -glucose has been investigated in this regard, − and we took interest in measuring l -glucose in aqueous buffers and blood samples. Monitoring of blood d -glucose is important for the treatment of diabetes, and various devices are available for fast d -glucose measurements, using “strips” with handy glucometers for spot checks of d -glucose in small blood samples (finger pricks), or using small electrodes that are inserted under the skin, for continuous d -glucose readings over days or weeks.…”

Section: Introductionmentioning

confidence: 99%

Diboronate Fluorophore for the Measurement of l-Glucose and Other Carbohydrates and Its Interaction with Albumin

et al. 2022

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l -Glucose has recently been investigated as an artificial sweetener, but no facile method is established for the measurement of l -glucose. The commercial probe Eversense employs a fluorescent diboronate in a small device for the optical monitoring of d -glucose in people with diabetes. Being achiral, the Eversense probe should be able to detect l -glucose as well as native d -glucose, but the probe is designed for fixation under the skin, and our attempts to use the probe at laboratory conditions failed, as the probe was resetting when moved between compartments. We thus designed a water-soluble anthracene diboronate 8 similar to the fluorophore used in Eversense and found 8 to respond well to l -glucose and other carbohydrates and artificial sweeteners, thus enabling measurements of l -glucose with the limit of quantification of 12 μM. Notably, the fluorescent signal of diboronate 8 was largely quenched in buffers with the physiological concentration of albumin (0.5 mM), so the given analytical method would need more optimization to be useful for measuring l -glucose and other carbohydrates in blood samples. We suspect that other diboronate fluorophores from the literature may be similarly quenched if applied in the presence of albumin.

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

Cited by 14 publications

References 63 publications

Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers

Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers

TAS1 receptors. An overview of their functions, expression and genetic variations

Diboronate Fluorophore for the Measurement of l-Glucose and Other Carbohydrates and Its Interaction with Albumin

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