Metals help sniff out offensive odors

October 4, 2016 § Leave a comment

Sketch by Hanyi Zhuang

Sketch by Hanyi Zhuang

What do skunks, decomposing cadavers and garlic have in common? Their odors contain sulfur. Humans are very sensitive to those odors. We’re able to pick up mere whiffs of them.

A team of researchers now report that they have found the olfactory receptor that gives us this exquisite sensitivity to sulfur-containing compounds. The receptor, known as OR2T11, requires metals for its activation. The finding, published in the Journal of the American Chemical Society, is the first to report the activation of a human olfactory receptor solely by metals.

Genetically speaking, olfactory receptors come in large numbers. There are about 400 genes for olfactory receptors in humans and 1,200 in mice. Figuring out which olfactory receptor picks up which scent is a challenge.

Finding OR2T11 demanded a multifaceted team. Victor Batista at Yale University, Lucky Ahmed and their group brought computational modeling expertise to the project. Eric Block at the University at Albany, State University of New York, is a chemist interested in organosulfur compounds and their smells. Jessica Burger at the National Institute of Standards and Technology in Boulder, Colorado, is a specialist in nuclear magnetic resonance spectroscopy. Hanyi Zhuang at the Shanghai Jiaotong University School of Medicine in China and colleagues are neuroscientists with expertise in olfactory receptors.

Zhuang’s laboratory has a cell-based system that can effectively express olfactory receptors. She says, “In this study, this platform enabled high-throughput screening of a human odorant receptor library and led to the discovery of the highly responsive thiol receptor OR2T11.”

The investigators discovered that OR2T11 was particularly sensitive to picking up tertiary-butyl mercaptan, also named 2-methyl-2-propanethiol, as well as ethanethiol. These two compounds are interesting because they are used in the fuel industry. With fuels, a very serious problem, called odor masking, occasionally arises. “Fuels sometimes cannot be smelled because of a combination of intermolecular and physiological interactions,” says Burger. “Utilities purchase fuel gas but, upon delivery, sometimes notice that there is little detectable or recognizable odor.”

Tertiary-butyl mercaptan is the main odorizing agent added to highly flammable natural gas, which is itself odorless. Ethanethiol gets added to liquified petroleum gas, which is also odorless and flammable. Both compounds give humans a warning smell if the fuels escape from containers.

The investigators also discovered that the receptor is activated by copper or silver. Although Zhuang says that the possible involvement of metal in olfaction has been proposed by chemists even before the cloning of the odorant receptors, Block adds, “there was only very limited experimental evidence for the role of metals in olfaction.”

The Batista group’s computations backed up the investigators’ experimental findings. The computations, Batista says, “enabled us to build a fully atomistic molecular model of the human odorant receptor with copper or silver binding sites for organosulfur compounds” that were consistent with experimental observations.

The investigators also were struck by how OR2T11 responds only to low-molecular-weight thiols — those with five or fewer carbon atoms — even though thiols with six or more carbons also have strong odors. Block says the finding indicates that size matters when dealing with particular classes of odorants interacting with their most responsive olfactory receptors.

Given that ionic and nanoparticulate silver can activate the receptor and enhance its sensitivity to sulfur-based compounds, Block notes there can be environmental issues. The finding “is a potentially important observation given that there are concerns about nanoparticulate metals in the environment, for example in bodies of water, which could impact olfaction in fish,” he says.

 

 

 

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