Module 2 - taste

Question 1

Sweet

Answer 1

2 receptors

T1R2/TIR3

Question 2

Umami (savoury)

Answer 2

2-4 receptors

T1R1/T1R3

Question 3

Sour

Answer 3

PDK1L3, PDK2L1

Question 4

Bitter

Answer 4

3-49 receptors

T2R

Question 5

Type I cell

Answer 5

Support
Degrade/absorb NTs
May clear EC K+

Question 6

Type II

Answer 6

GPCR, expresses related to sweet, bitter
Sensory
Requires Type III to transmit taste perception
Activated by sweet, bitter and umami taste comounds - induce them to release ATP

Question 7

Type III

Answer 7

Synapsis, forms synapses with afferent nerve
Presynaptic
Release serotonin (5-HT)&raquo_space; inhibits receptor cells

Question 8

Taste transduction

Answer 8

Ligand binding to receptor causes G Protein to activate and phosphorylate PLCB2. Converted to IP3 and DAG. IP3 releases IP3R3 which activates rc at ER. Calcium is released and activates TRPM5, Na is released and causes depolarisation, causing a burst of APs which then result in the release of NTs (ATP)

Question 9

T2Rs

Answer 9

Do not co-localise with T1Rs
Always co-localise with GalphaGustducin
Express PLCBeta2 and TrpM5

Question 10

T1R2 + T1R3

Answer 10

Sweet receptor

expressing taste cells express Galpha14

Question 11

Taste and hunger satiety cycle

Answer 11

Taste-rc cells in tongue - stimuli triggers synapses w/ nerve fibers&raquo_space; info to hindbrain

In enteroendocrine cells - trigger release of signalling molecules i.e. satiation peptides

Question 12

Orthosteric agonists

Answer 12

L-aa, divalent cations, sugars
Activate LBD, excite rc and then taste
Goes to main LBD

Question 13

Allosteric enhancers

Answer 13

L-aa, divalent cations
Also purinic nucleotides
Gd3+, Ca2+?
Does not stimulate rc - doesn’t go to main LBD - but needs main agonist to ENHANCE the sensitivity. Absence of agonist results in no signal.

Question 14

Allosteric agonists

Answer 14

Brazzein

Ligands do not excite the main LBD, stimulate rc through other sites

Question 15

Allosteric modulator

Answer 15

Drug-like small molecules

Question 16

Allosteric activation of the Human Sweet Taste Receptor (T1R2/T1R3)

Answer 16

???

Question 17

Negative allosteric modulation - lactisole

Answer 17

Binds human T1R3, inhibits activation of T1R1-T1R3 umami faste rc but lower affinity than with sweet taste receptor. Changes conformation and are no longer activated by sugars.
Inhibitory effect of it on umami is blocked when MSG is mixed with GMP/IMP

Question 18

Venus Fly Trap Domain - umami

Answer 18

Big binding pocket. Glutamate (activator) goes deep inside it and induces closure. IMP binds close to the opening and helps stabilise the closed conformation of the rc. They both interact with VFT domain of T1R1 but at different binding sites. L-glutamate and purinic nucleotides synergise with each other. Allosteric enhancers further increase the sensitivity of the umamim taste rc.

Question 19

Miraculin case study

Answer 19

Normally not sweet, however pH decreases, conformation of protein of mraculin changes, stimulates/activates TIR2 and transforms acidity into sweetness.

Question 20

Taste of carbonation

Answer 20

Requires PDK2L1-sour cells and Carbonic Anhydrase (Car4). CO2 also stimulates somatosensory system.

DZA = Dorzolamide, a carbonic anhydrase blocker

Question 21

Taste of NaCl (salt)

Answer 21

Salt taste = NaCl in humans
High Na consumption = HTN, CVD and stroke, therefore reduction is ideal
Two models: A = tetrameric assembly of ENaC subunits around the central pore (a, b, y, o)