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New Research Digs Into the Bitter Truth About Coffee

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For better or worse, one of the defining tastes of coffee — the life-giving elixir that makes the world go ’round — is bitterness

A new study involving researchers at the University of North Carolina at Chapel Hill offers a molecular-level look at why coffee tastes bitter, showing how the body detects certain bitter compounds in the cup.

Published April 20 in Nature Structural & Molecular Biology, the research shows how the human bitter taste receptor TAS2R43 recognizes caffeine and other compounds naturally found in roasted, brewed coffee. 

Bitterness in Coffee

The work is not a tasting trial or a brewing study. Instead, it is structural biology.

The team used cryo-electron microscopy — a technique that flash-freezes biological molecules and uses electrons to create detailed 3D images — to capture the structure of TAS2R43. The receptor has been identified as key for detecting coffee’s bitterness, including from caffeine, cafestol and mozambioside.

“Before this study, we did not know how coffee bitterness is initiated at the molecular level, because there was no three-dimensional structure showing how the bitter taste receptor TAS2R43 recognizes bitter tastants,” study first author Yoojoong Kim said in an announcement from the university. 

Perhaps most importantly for coffee, the study confirmed that TAS2R43 responds not just to caffeine but to a broader set of coffee-derived compounds.

Cafestol and kahweol, the oily diterpenes prominent in unfiltered coffee preparations such as French press and Turkish coffee, activated the receptor at particularly high levels, as did catechol and chlorogenic acid. The findings support the idea that coffee’s bitterness involves multiple compounds acting on TAS2R43, not caffeine alone.

Broader Research Implications

Looking beyond the taste of coffee, the research team suggested the work could potentially help lead to practical applications in the field of medicine. Bitter taste receptors are known to be helpful in humans in naturally detecting toxins, pathogens or harmful bacteria.

According to senior and corresponding author Bryan L. Roth of the UNC School of Medicine, bitter taste receptors like TAS2R43 are expressed throughout the body, “where they have been proposed to act as both defense mechanisms against potentially toxic substances and for metabolic regulation.”

Roth said the discovery of the molecular mechanisms explaining interactions between coffee compounds and bitter taste receptors could help “provide new therapeutic strategies for a number of diseases.”

In the study’s “competing interests” section, Roth declared affiliations with numerous pharmaceutical companies. He is listed as the co-founder of ImprintBio, Lassogen and Epiodyne and as a scientific advisory board member to Septerna and Lassogen. The work was supported by the National Institute of Mental Health Psychoactive Drug Screening Program


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