The senses constitute the primary vehicle through which humans interact with their surroundings. Take a simple cup of morning coffee! Everything that one enjoys about that coffee is enabled by our body’s highly evolved senses. The complex bitterness of a Colombian dark roast is facilitated by the interaction of caffeine molecules with bitterness receptors on our tongue. The sweetness of a rich frappé is due to the interaction of sugars like sucrose with sweetness receptors.

By Roshan G Bhaskar

We experience the hotness of freshly poured filter coffee and the coldness of an iced coffee because of the reaction of a family of heat and cold receptors on our tongue to changes in temperature. Every sense of ours — sight, hearing, taste, smell, touch, temperature, pain, itch, balance, and even mood — boils down to the interaction between stimuli (photochemical, mechanical, or chemical) from our environment and various receptors in the body.

Human sensory ability is an exciting area of chemical neuroscience with the field being the recipient of the 2021 Nobel Prize in Physiology and Medicine (David Julius and Ardem Patapoutian for their discovery of temperature and touch receptors). However, as fascinating as each sense of the human body is, the remainder of this article will focus primarily on the sense of taste.

So, how is a molecule of sucrose (sugar) on the tongue interpreted by our brain as ‘sweet’?

Receptors are specialised proteins in our body that detect external stimuli (such as the molecules in food) and consequently trigger specific sequences of chemical reaction (or “pathways”).

GPCRs (G Protein-Coupled Receptors) are a subfamily of receptors responsible for the detection of sweetness, bitterness, and umami. When a sweet molecule such as sucrose comes in contact with (or “binds” with) a sweetness-sensing GPCR on our tongue, the shape of the GPCR changes. This change in shape or “conformational change” activates a second protein (a “G Protein”) which in turn triggers further chemical events.

This cascade of chemical events (or pathway) ultimately leads to an increase of calcium ions (Ca2+) in the cells of our taste buds, which releases yet another molecule (a neurotransmitter in this case) that activates our nervous system. This neurotransmitter hits the sensory nerves, which carry the message of ‘sweetness’ to our brain in the form of electrical impulses.

Any molecule (simple sugar or not) that binds to a sweetness-sensing GPCR will induce the sensation of sweetness through this pathway. This is the principle behind the use of sugar substitutes in ‘diet’ drinks. Aspartame, one of the most common sugar substitutes, hits the same sweetness-sensing GPCRs that sucrose (sugar) does, but is metabolised into lower caloric, non-sugar byproducts.

Sweetness-sensing GPCRs can also be targeted by small proteins. Miraculin, a small protein found in the aptly named ‘Miracle fruit’, activates sweetness-sensing GPCRs only under acidic conditions. On its own, miraculin has no taste, but when paired with something sour (acidic), such as lemon juice, it makes the ordinarily sour lemon juice taste sweet through its conditional activation of sweetness-sensing GPCRs!

Miraculin currently has FDA (the United States Food and Drug Administration) approval as a food additive and research is ongoing into the use of miraculin as a potential low-calorie sweetener.

Analogous to ‘sweet’ molecules activating sweetness-sensing GPCRs, there are specific molecules that activate bitterness-sensing GPCRs. The unpleasantness that we associate with ‘bitterness’ is an evolutionary response against potentially toxic or poisonous molecules. For this reason, bitterness seems to have evolved as the most sensitive taste with there being 25 types of bitterness-sensing GPCRs relative to just the two types of sweetness-sensing GPCRs that exist in humans.

Molecules such as caffeine (found in coffee), ethanol (found in alcoholic beverages), absinthin (found in absinthe), and quinine exemplify the idea of the unpleasant sensation of bitterness having evolved as a defence mechanism to potentially toxic or poisonous molecules.

Andrographolide, a molecule isolated from the Ayurvedic plant Andrographys paniculata (King of Bitters), is one of the most bitter natural compounds known and works through the activation of these same bitterness-sensing GPCRs.

The sense of umami or savoury is perceived by the interaction between amino acids in food and umami-sensing GPCRs on our tongue. The most well-known molecule responsible for umami is the amino acid L-glutamate (the “G” in MSG or monosodium glutamate).

Another common food product associated with umami is matcha (Japanese green tea), the cultivation of which began during the 1100s in Japan. Fast forward to the twenty-first century where matcha is now a global phenomenon, appreciated for its complex, rich, and aromatic flavour profile. This complex flavour profile is due to a combination of “sweet” molecules that target sweetness-sensing GPCRs and umami molecules (L theanine and theogallin) that target umami-sensing GPCRs.

What humans perceive as the taste of saltiness is the detection of sodium ions (the “sodium” in sodium chloride or table salt) in food. Unlike that of sweetness, bitterness, and umami, the sensation of saltiness is not detected by a GPCR but by two different receptors – cation channels named ENaC and TRPV1t.

TRPV1t, in addition to being stimulated by sodium ions (or salt), is also stimulated by capsaicin (the molecule that makes chilli peppers spicy). This is why chilli peppers, in addition to being spicy, also taste salty.

Finally, sourness – arguably the least well-understood of the sensations of taste. Lemons, yoghurt, and vinegar – three conventionally sour foods – contain citric acid, lactic acid, and acetic acid respectively, suggesting that ‘acidity’ and sourness are related. The chemical definition of an acid is a molecule that can donate protons. The protons donated by citric acid, lactic acid, and acetic acid are detected by OTOP1 (the ‘sourness receptor’), resulting in our perception of lemons, yoghurt, and vinegar as sour.

We now know how our brain interprets the flavour of caffeine as bitter, that of sugar as sweet, that of lactic acid as sour, and that of L-theanine as umami when we drink a matcha green tea latté. The intricate dance of different molecules and receptors on our tongue gives rise to the complexity of flavours that we appreciate in good food.

However, taste is not the only sense involved in our experience with food; the perception of smell and temperature also play a key role. Much like taste, smell and temperature are also detected by their own host of receptors, detailed descriptions of which are beyond the scope of this article.

Suffice it to say that ongoing research into sensory receptors in our body (whether it be taste, smell, temperature, pain, light, touch, or balance receptors) continues to elucidate the various mysteries behind the interaction between humankind and the world we live in.

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