Reactome | Sensory perception of sweet, bitter, and umami (glutamate) taste

Sensory perception of sweet, bitter, and umami (glutamate) taste

Stable Identifier

R-HSA-9717207

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Sensory perception of sweet, bitter, and umami (glutamate) taste

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Taste receptors for bitter compounds, sweet compounds, and umami compounds (L-glutamate in humans, several amino acids in mice) are G protein-coupled receptors located in type II taste bud cells that signal through a common downstream pathway (reviewed in Margolskee 2002, Kinnamon 2009, Kurihara 2015, Roper and Chauhari et al. 2017, Kinnamon and Finger 2019, Servant et al. 2020). Umami ("savoury", L-glutamate) taste receptors are heterodimers of the plasma membrane proteins TAS1R1 and TAS1R3. TAS1R1:TAS1R3 heterodimers also bind 5' nucleotides such as 5' IMP which synergistically augment umami taste. The glutamate receptors GRM1 (mGluR1) and GRM4 (mGluR4) act in an alternative pathway for sensing glutamate in taste cells (reviewed in Chaudhari et al. 2009). Sweet taste receptors are heterodimers of the plasma membrane proteins TAS1R2 and TAS1R3 (reviewed in Yang et al. 2021). The glucose transporters SGLT1 and GLUT4 are expressed in type II taste cells and may provide an alternative pathway for sensing glucose (reviewed in von Molitor et al. 2020). Bitter receptors are a large family of monomeric plasma membrane proteins, the TAS2R proteins.
TAS1R-containing sweet and umami receptors and TAS2R bitter receptors are each physically associated with a particular heterotrimeric G protein complex, the gustducin complex, containing GNAT3 (gustducin), GNB1 or GNB3, and GNG13. Upon binding an agonist ligand, the receptor activates the alpha subunit, GNAT3, to exchange GDP for GTP, which results in a conformational change in GNAT3 that causes the receptor-gustducin complex to dissociate, yielding GNAT3:GTP, GNB1,3:GNG13, and the receptor:ligand. The GNB1,3:GNG13 complex binds and activates Phospholipase C beta-2 (PLCB2), which then hydrolyzes phosphoinositol 4,5-bisphosphate (PI(4,5)P2) to yield diacylglycerol and inositol 1,4,5-trisphosphate (I(1,4,5)P3). I(1,4,5)P3 binds and activates the calcium channel IP3-gated Ca-channel type 3 (ITPR3) and ITPR3 then releases calcium ions from the endoplasmic reticulum into the cytosol. The increased cytosolic calcium activates the TRPM5 cation channels, which then transport sodium ions along the concentration gradient from the extracellular region to the cytosol (reviewed in Aroke et al. 2020). The depolarization activates SCN2A, SCN3A, and SCN9A channels, which transport further sodium ions from the extracellular region to the cytosol. The depolarization of the plasma membrane opens CALHM1:CALHM3 channels, which transport ATP, a neurotransmitter in the olfactory system, from the cytosol to the extracellular region.
Taste receptors were initially discovered in taste buds of the tongue and have now been found in several other tissues including nasal epithelium (Barnham et al. 2015, inferred from rodent homologs in Tizzano et al. 2011), the respiratory system, pancreatic islet cells, sperm (Governini et al. 2020), leukocytes (Malki et al. 2015), and enteroendocrine cells of the gut (inferred from rat and mouse homologs in Wu et al. 2002).

Literature References

PubMed ID	Title	Journal	Year
32185015	Recent advances in taste transduction and signaling Kinnamon, SC, Finger, TE	F1000Res	2019
31963712	Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm Governini, L, Semplici, B, Pavone, V, Crifasi, L, Marrocco, C, De Leo, V, Arlt, E, Gudermann, T, Boekhoff, I, Luddi, A, Piomboni, P	J Clin Med	2020
32824721	Taste the Pain: The Role of TRP Channels in Pain and Taste Perception Aroke, EN, Powell-Roach, KL, Jaime-Lara, RB, Tesfaye, M, Roy, A, Jackson, P, Joseph, PV	Int J Mol Sci	2020
26247011	Umami the Fifth Basic Taste: History of Studies on Receptor Mechanisms and Role as a Food Flavor Kurihara, K	Biomed Res Int	2015
23404938	Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa Barham, HP, Cooper, SE, Anderson, CB, Tizzano, M, Kingdom, TT, Finger, TE, Kinnamon, SC, Ramakrishnan, VR	Int Forum Allergy Rhinol	2013
32607758	Current Progress in Understanding the Structure and Function of Sweet Taste Receptor Yang, L, Cui, M, Liu, B	J Mol Neurosci	2021
11696554	Molecular mechanisms of bitter and sweet taste transduction Margolskee, RF	J Biol Chem	2002
19571230	Taste receptors for umami: the case for multiple receptors Chaudhari, N, Pereira, E, Roper, SD	Am J Clin Nutr	2009
19571214	Umami taste transduction mechanisms Kinnamon, SC	Am J Clin Nutr	2009
33030576	An alternative pathway for sweet sensation: possible mechanisms and physiological relevance von Molitor, E, Riedel, K, Krohn, M, Rudolf, R, Hafner, M, Cesetti, T	Pflugers Arch	2020
32416872	The function and allosteric control of the human sweet taste receptor Servant, G, Kenakin, T, Zhang, L, Williams, M, Servant, N	Adv Pharmacol	2020
28655883	Taste buds: cells, signals and synapses Roper, SD, Chaudhari, N	Nat Rev Neurosci	2017
25624459	Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes Malki, A, Fiedler, J, Fricke, K, Ballweg, I, Pfaffl, MW, Krautwurst, D	J Leukoc Biol	2015