Recognizing foods, predators, and pests by their smell is of key evolutionary significance in many species, including humans. Smell relies on molecular recognition—the precise binding of a volatile molecule emanating from the source to a specific receptor protein in the nasal lining of an organism.

Pyrazines are such volatile cues. Some are key food odorants (KFOs) and others are semiochemicals—chemicals that convey signals from one organism to another to modify behavior in recipients.

The receptor protein in mammals that can detect pyrazines had not been known, until now.

In a new study, scientists at the Leibniz Institute for Food Systems Biology in Germany and their collaborators screened 616 human odorant receptors against a pyrazine that acts as a KFO and a semiochemical (2,3,5-trimethylpyrazine) and a pyrazine associated with fear (2,5-dihydro -2,4,5-trimethylthiazoline) to identify the only responsive receptor, OR5K1.

The authors tested the new receptor against 178 KFOs and identified 18 pyrazines and 2 non-pyrazines that bind to OR5K1. The researchers have also identified OR5K1 orthologs in mouse and domesticated species that bind to pyrazines in a similar manner as in humans. This, the authors note, suggests co-evolution of the receptor through domestication.

These findings are published in The FASEB Journal article, An evolutionary conserved olfactory receptor for foodborne and semiochemical alkylpyrazines.” The study offers insights into the molecular mechanisms underlying how we perceive food and communicate through smell.

Despite intensive research, the specific odorant spectrum detected by nearly 80 percent of human receptors for smell is still unknown. Findings such as those reported in this study can provide insights into the physiological functions of these receptors that go beyond the sensory perception of food and help develop bio-based artificial noses that can be used to monitor the sensory quality and authenticity of food.

Franziska Haag, PhD and Dietmar Krautwurst, PhD, in front of the high-throughput pipetting and measuring robot (TECAN Fluent) they use to investigate odorants that human olfactory receptors sense [Leibniz-LSB@TUM]
“In particular, odorants such as pyrazines are interesting in this regard. This is because some of them, as key odorants, shape the typical aroma of food and, at the same time, play a major role as volatile signaling substances in olfactory communication of animals. A good example is wolves, which leave scent messages in their territory via their urine and thus mark it,” says Dietmar Krautwurst, PhD, who heads the program in Chemoreception & Biosignaling of the Leibniz Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany.

Trimethylpyrazine is formed during roasting. Its scent is reminiscent of baked potatoes, roasted nuts and cocoa and is frequently used as a flavoring agent in the food industry. It is also present in the urine of foxes and wolves and alerts mice and other prey.

That the human olfactory receptors can detect pyrazines was not known. The research team used a new cellular assay system established at the institute to investigate the responses of over human receptor variants to trimethylpyrazine.

Patrick Marcinek, PhD, first author on the study, analyzes cells with a flow cytometer at the Leibniz Institute for Food Systems Biology at the Technical University of Munich [C. Schranner / Leibniz-LSB@TUM]
“Strikingly, those pyrazines, which activate the receptor most potently, function both as food odorants and signaling substances in the animal kingdom,” says Franziska Haag, PhD, of the Leibniz Institute of Food Systems Biology at the Technical University of Munich, who, together with first author Patrick Marcinek, PhD, played a key role in the study.

Veronika Somoza, PhD, director of the Leibniz Institute says, “In the future, we will use our unique, extensive odorant and receptor collection at the institute to decipher the function of human olfactory receptors.”