Sweet and Umami Taste: Natural Products, Their Chemosensory Targets, and Beyond

Behrens, Maik; Meyerhof, Wolfgang; Hellfritsch, Caroline; Hofmann, Thomas

doi:10.1002/anie.201002094

Cited by 167 publications

(165 citation statements)

References 198 publications

(308 reference statements)

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“…that interacts with the ATD of hT1R2 (12). As expected, mT1R2-mT1R3 did not respond to acidic stimulation after MCL preincubation, whereas hT1R2-hT1R3 did (Fig.…”

Section: Resultssupporting

confidence: 74%

“…It has been reported that the acid-induced sweetness of MCL is diminished by a sweet taste inhibitor, lactisole (11), which inhibits hT1R2-hT1R3 by interacting with the transmembrane domain (TMD) of the hT1R3 subunit (12). This finding strongly indicates that MCL acts through the hT1R2-hT1R3.…”

Section: Resultsmentioning

confidence: 98%

“…T1R is composed of three domains: an ATD, a cysteine-rich domain (CRD), and a TMD and it is known that hT1R2-hT1R3 possesses multiple ligand-binding sites for different sweeteners (12). Here, we identified which part of hT1R2-hT1R3 is involved in the response to MCL.…”

Section: Resultsmentioning

confidence: 99%

“…6B shows a docking model in which the intermolecular interactions occur at this region. Although the interface on hT1R2 probably extends outside of this region and some conserved residues between human and mouse may be involved in the binding and the activation, the MCL binding site is clearly different from the hinge region of hT1R2 ATD, to where representative low molecular-weight sweeteners are bound (12).…”

Section: Resultsmentioning

confidence: 99%

“…4). These sweeteners are known to interact with different regions of hT1R2-hT1R3: aspartame and D-Trp interact with hT1R2 ATD, NCL interacts with hT1R3 ATD, brazzein interacts with hT1R3 CRD, and cyclamate and neohesperidin dihydrochalcone (NHDC) interact with hT1R3 TMD (12,26). It is to be noted that the region required for the response to MCL, the 448 to 494 aa in hT1R2 ATD is clearly different from the hinge regions of ATD that binds low-molecular sweeteners (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Human sweet taste receptor mediates acid-induced sweetness of miraculin

Koizumi¹,

Tsuchiya²,

Nakajima³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pHdependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity.G protein-coupled receptor | positive allosteric modulator | taste-modifying protein | calcium imaging

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“…that interacts with the ATD of hT1R2 (12). As expected, mT1R2-mT1R3 did not respond to acidic stimulation after MCL preincubation, whereas hT1R2-hT1R3 did (Fig.…”

Section: Resultssupporting

confidence: 74%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Human sweet taste receptor mediates acid-induced sweetness of miraculin

Koizumi¹,

Tsuchiya²,

Nakajima³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Bitter Taste Sensitivity in Humans and Chimpanzees

Behrens

Meyerhof

2013

Encyclopedia of Life Sciences

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Bitter taste receptors (TAS2Rs) serve an important function during evolution. They are designed to detect toxic plant metabolites before ingestion. With respect to bitter taste receptors the genetic repertoire of animal species is highly diverse reflecting the species differences in their metabolic requirements, the variety of habitats and evolutionary history. Over the recent years, an incredible amount of data on human bitter taste receptor pharmacology, biochemistry and structural features has accumulated. It became apparent that TAS2R gene expression is not restricted to the oral cavity, but includes several nongustatory tissues, thus expanding the presumed roles of TAS2Rs. By comparing the bitter taste receptor genes of humans with our closest relative, the chimpanzee, we learn about some of the evolutionary forces that shaped the development of modern human beings. This article discusses the current knowledge on bitter taste physiology, TAS2R function and evolutionary conservation of human and chimpanzee TAS2R genes. Key Concepts: Taste physiology and hedonics of bitter taste appear similar in humans and chimpanzees. Human bitter taste receptors can be grouped into generalists and specialists depending on their tuning breadth. Similar to the human situation, bitter tasting abilities of the chimpanzee are in some instances individual. Dynamic evolution of human and chimpanzee TAS2R genes is earmarked by regional diversification. The rate of TAS2R gene pseudogenisation indicates relaxed evolutionary constraints in the primate lineage.

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New Developments in Sweeteners

Servant¹,

Rosenberg²

2012

Sweeteners and Sugar Alternatives in Food Technology

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Sweet and Umami Taste: Natural Products, Their Chemosensory Targets, and Beyond

Cited by 167 publications

References 198 publications

Human sweet taste receptor mediates acid-induced sweetness of miraculin

Human sweet taste receptor mediates acid-induced sweetness of miraculin

Bitter Taste Sensitivity in Humans and Chimpanzees

New Developments in Sweeteners

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