Editing Umami (section)

==Taste receptors==
{{See also|Taste receptor#Savory or glutamates (Umami)}}
Most [[taste bud]]s on the tongue and other regions of the mouth can detect umami taste, irrespective of their location. (The [[tongue map]] in which different tastes are distributed in different regions of the tongue is a common misconception.) [[Biochemical]] studies have identified the [[taste receptor]]s responsible for the sense of umami as modified forms of [[Metabotropic glutamate receptor 4|mGluR4]], [[Metabotropic glutamate receptor 1|mGluR1]], and [[taste receptor]] type 1 ([[TAS1R1]] + [[TAS1R3]]), all of which have been found in all regions of the tongue bearing taste buds.<ref name = "Chaudhari_2000">{{cite journal | vauthors = Chaudhari N, Landin AM, Roper SD | title = A metabotropic glutamate receptor variant functions as a taste receptor | journal = Nature Neuroscience | volume = 3 | issue = 2 | pages = 113–9 | date = February 2000 | pmid = 10649565 | doi = 10.1038/72053 | s2cid = 16650588}}
*{{cite press release |date=February 2000 |title=Umami taste receptor identified |website=Nature Neuroscience |url=http://www.nature.com/neuro/press_release/nn0200.html |archive-url=https://web.archive.org/web/20130305013817/http://www.nature.com/neuro/press_release/nn0200.html |archive-date=2013-03-05}}</ref><ref name="Nelson_2002"/><ref>{{cite journal | vauthors = San Gabriel A, Uneyama H, Yoshie S, Torii K | title = Cloning and characterization of a novel mGluR1 variant from vallate papillae that functions as a receptor for L-glutamate stimuli | journal = Chemical Senses | volume = 30 Suppl 1 | issue = Suppl | pages = i25-6 | date = January 2005 | pmid = 15738140 | doi = 10.1093/chemse/bjh095 | doi-access = free}}</ref> These receptors are also found in some regions of the [[duodenum]].<ref name="Sasano_2015">{{Cite journal| vauthors = Sasano T, Satoh-Kuriwada S, Shoji N |date=2015-01-26|title=The important role of umami taste in oral and overall health |journal= Flavour|volume=4|issue=1|pages=10|doi=10.1186/2044-7248-4-10|s2cid=14562283|issn=2044-7248|doi-access=free}}</ref> A 2009 review corroborated the acceptance of these receptors, stating, "Recent molecular biological studies have now identified strong candidates for umami receptors, including the heterodimer TAS1R1/TAS1R3, and truncated type 1 and 4 metabotropic glutamate receptors missing most of the N-terminal extracellular domain (taste-mGluR4 and truncated-mGluR1) and brain-mGluR4."<ref name="Symposium">{{cite book |editor-last1=Finger |editor-first1=Thomas E.  |year=2009 |title=International Symposium on Olfaction and Taste |language=English |volume=1170 |edition=1st |location=Hoboken, NJ |publisher=Wiley-Blackwell |isbn=978-1573317382}}</ref>

Receptors mGluR1 and mGluR4 are specific to glutamate whereas TAS1R1 + TAS1R3 are responsible for the synergism already described by Akira Kuninaka in 1957. However, the specific role of each type of receptor in taste bud cells remains unclear.<ref name=Diepeveen/> All three receptors work together to produce the taste sensation.<ref>{{cite journal |last1=Yasumatsu |first1=K |last2=Manabe |first2=T |last3=Yoshida |first3=R |last4=Iwatsuki |first4=K |last5=Uneyama |first5=H |last6=Takahashi |first6=I |last7=Ninomiya |first7=Y |title=Involvement of multiple taste receptors in umami taste: analysis of gustatory nerve responses in metabotropic glutamate receptor 4 knockout mice. |journal=The Journal of Physiology |date=15 February 2015 |volume=593 |issue=4 |pages=1021–34 |doi=10.1113/jphysiol.2014.284703 |pmid=25529865|pmc=4398535 }}</ref>

=== Downstream signaling ===
==== TAS1R1 + TAS1R3 ====
The TAS1R1 + TAS1R3 receptor is a [[G protein-couple receptor]], much like the sweet and bitter receptors. It uses the same downstream signaling molecules, including [[G beta-gamma complex|G proteins beta-gamma]], [[PLCB2]] and [[Inositol triphosphate|IP<sub>3</sub>]], to ultimately cause a release of [[calcium]] (Ca<sup>2+</sup>) from intracellular stores.<ref name=Kinnamon>{{cite journal | author = Kinnamon SC | title = Taste receptor signalling – from tongues to lungs | journal = Acta Physiologica | volume = 204 | issue = 2 | pages = 158–68 | date = February 2012 | pmid = 21481196 | pmc = 3704337 | doi = 10.1111/j.1748-1716.2011.02308.x}}</ref> Calcium activates a so-called transient-receptor-potential cation channel [[TRPM5]] that leads to membrane [[depolarization]] and the consequent release of [[Adenosine triphosphate|ATP]] across a channel of [[CALHM1]] and [[CALHM3]].<ref name=Diepeveen>{{cite journal |last1=Diepeveen |first1=J |last2=Moerdijk-Poortvliet |first2=TCW |last3=van der Leij |first3=FR |title=Molecular insights into human taste perception and umami tastants: A review. |journal=Journal of Food Science |date=April 2022 |volume=87 |issue=4 |pages=1449–1465 |doi=10.1111/1750-3841.16101 |pmid=35301715|pmc=9314127 }}</ref>

The ATP released by the "Type II" cell is detected by P2X receptors on nearby afferent gustatory nerve fibers and P2Y receptors on adjacent taste cells. P2X appears to be indispensable for the transduction of umami, so this is probably the main route for umami signals.<ref name=Kinnamon/> "Type III" cells, which directly connect to the nerve synapses, also respond to the released ATP by releasing neurotransmitters. One of these neurotransmitters, [[serotonin]], regulates the release of ATP by the type II cells.<ref name=Kinnamon/>

==== mGluR1 and mGluR4 ====
Signal from these two receptors are conveyed in a manner independent of TRPM5. Single umami-sensitive fibres in mice are mostly either "sucrose-best" or "glutamate-best". Within each type there are two subtypes: one shows synergistic activation between monopotassium glutamate and inosine monophosphate, the other does not. The TAS1R1/3 + TRPM5 route uses the "sucrose-best" fibers with synergy, while mGluR1 and mGluR4 use both of the "glutamate-best" subtypes.<ref>{{cite journal |last1=Yasumatsu |first1=Keiko |last2=Ogiwara |first2=Yoko |last3=Takai |first3=Shingo |last4=Yoshida |first4=Ryusuke |last5=Iwatsuki |first5=Ken |last6=Torii |first6=Kunio |last7=Margolskee |first7=Robert F. |last8=Ninomiya |first8=Yuzo |title=Umami taste in mice uses multiple receptors and transduction pathways |journal=The Journal of Physiology |date=March 2012 |volume=590 |issue=5 |pages=1155–1170 |doi=10.1113/jphysiol.2011.211920 |pmid=22183726|pmc=3381822 }}</ref>

=== Beyond the tongue ===
The gut has its own umami taste receptors. The ATP taste signals are conveyed to the brain, probably through afferent branches of the [[vagus nerve]] or the afferent sensory nerves in the mouth. The brain uses this information to regulate behaviors and preferences in mice. This is an example of the [[gut-brain axis]].<ref name="Torii_2013"/>

=== In other animals ===
Cats have mutations in Tas1r1 and Tas1r3 that cause their receptor to not perceive glutamate and aspartate as umami. However, their rececptor responds to nucleotide, and some L-amino acids enhance the response to nucleotides. Cats probably perceive tuna as very umami due to it being rich in [[Inosinic acid|inosine monophosphate]] and L-histine.<ref name=McGrane>{{cite journal |last1=McGrane |first1=Scott J. |last2=Gibbs |first2=Matthew |last3=Hernangomez de Alvaro |first3=Carlos |last4=Dunlop |first4=Nicola |last5=Winnig |first5=Marcel |last6=Klebansky |first6=Boris |last7=Waller |first7=Daniel |date=August 8, 2023 |title=Umami taste perception and preferences of the domestic cat (Felis catus), an obligate carnivore |url=https://doi.org/10.1093/chemse/bjad026 |journal=Chemical Senses |volume=48 |doi=10.1093/chemse/bjad026 |pmid=37551788 |pmc=10468298 |access-date=September 21, 2023}}</ref>

The Tas1r1-Tas1r3 receptor of mice is activated by a wide range of free L-amino acids, but not acidic ones such as glutamate.<ref name=McGrane/>

The lineage of aquatic mammals including dolphins and sea lions have no functional Tas1r1, and neither do giant pandas. They cannot generate a functional Tas1r1-Tas1r3 receptor as a result.<ref name=":1">{{cite journal | vauthors = Jiang P, Josue J, Li X, Glaser D, Li W, Brand JG, Margolskee RF, Reed DR, Beauchamp GK |display-authors=3| title = Major taste loss in carnivorous mammals | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 13 | pages = 4956–61 | date = March 2012 | pmid = 22411809 | pmc = 3324019 | doi = 10.1073/pnas.1118360109 | doi-access = free }}</ref>