Research Reveals How We Perceive Bitter Taste

by Stephanie Feuer

Bitter is the of the five different tastes (sweet, sour, salty, bitter, and umami) that we can identify on our tongues using taste receptors. Our ability to detect bitter taste serves an important biological function, acting as a defense mechanism to prevent the ingestion of potentially toxic or poisonous substances. Humans have 26 different taste receptors, known as type 2 taste receptors, or TAS2Rs. One of these receptors, TAS2R14, is especially important, as it is capable of detecting 100 distinct bitter tastants. But until now, we haven’t known exactly how this works.

In a new study, published in the journal Nature, researchers at the UNC School of Medicine have revealed just how we perceive bitter. They found that when bitter tastants come into contact with TAS2R14 receptors, the chemicals wedge themselves into a specific spot on the receptor called an allosteric site. This causes the receptor to change its shape and activates the attached G protein.

This then triggers a series of biochemical reactions that activate the receptor and cause it to send signals via nerve fibers through the cranial nerves in the face to the gustatory cortex. It is there that the brain processes and perceives the signals as bitterness.

One unexpected finding was that the research team found cholesterol inside the TAS2R14 receptor binding site – the part of a molecule where it attaches to another molecule. The researchers suspect that cholesterol primes TAS2R14 so that it can be easily activated.

“Cholesterol was residing in another binding site called the orthosteric pocket in TAS2R14, while the bitter tastant binds to the allosteric site,” said Yoojoong Kim, PhD, a coauthor of the study. “Through molecular dynamics simulations, we also found that the cholesterol puts the receptor in a semi-active state, so it can be easily activated by the bitter tastant.”

Scientists have known that bile acids produced by the liver can bind to and activate the TAS2R14 receptor. Bile acids share a similar chemical structure with cholesterol. Leveraging the newly determined structure of TAS2R14, researchers discovered that bile acids might bind to the same orthosteric pocket as cholesterol does. While the precise function of bile acid or cholesterol binding to TAS2R14 is still unclear, it may be involved in the metabolism of these compounds or relate to metabolic disorders like obesity or diabetes.

In addition to the unexpected role of cholesterol, researchers found TAS2R14 outside the tongue, in places including the cerebellum in the brain, the thyroid, and the pancreas. They plan to further study the function these receptors may have outside of the mouth.

With these new insights into the mechanics of where and how bitter substances bind to TAS2R14 and understanding its activation mechanism, scientists have laid the groundwork for developing treatments that could regulate taste receptors to address conditions like obesity and diabetes.