Thanks to copper, sulfur’s stink repels us

DUKE (US) — Copper ions may be the cause of our sensitivity to sulfurous odors, like skunks, volcanic gases, and armpits.

When Hiroaki Matsunami, associate professor at Duke University, set out to study a chemical in male mouse urine called MTMT that attracts female mice, he didn’t think he would stumble into a new field of study.

But the research has led scientists to the discovery that it’s the copper in our bodies that makes mammals recoil from sulfurous chemical smells.

Working with Eric Block, professor of chemistry at the University of Albany, Matsunami’s team looked at reasons why mammals, including people, can detect even trace amounts of sulfur-containing substances, like MTMT.

“While we were doing our experiments, on even very dilute specimens of MTMT, our neighbors on the lab hallway complained,” Matsunami says with a laugh. He is an associate professor in the departments of molecular genetics and microbiology and of neurobiology.

The Duke laboratory ran a high-throughput test of several hundred mammalian odor receptors, and found that one receptor that bound copper ions resulted in superior detection of even trace amounts of sulfur.

Underarm odors from bacteria, skunk spray, volcanic gases, and odorized natural gas (for leak detection) are examples of sulfurous substances.

“We learned that copper was the metal that allowed for detection of all the sulfur-containing compounds we tested, and it was Eric Block’s idea that metal ions must be involved,” Matsunami says.

“Further, I see no reason why the mouse receptor activity would be different from human receptors, because we have the same kind of olfactory receptors.”

Block and colleagues created several dozen sulfur-containing compounds for testing.

The odor impact of the sulfur-containing molecule MTMT can be reduced by manipulating the copper concentration in the nasal mucus. The team did experiments using a chemical that binds to copper in the mouse nose, so that copper wasn’t available to the receptors, and the mice didn’t detect the MTMT, Matsunami says.

“This study establishes for the first time the key role of a metal, namely copper, in the activity of an olfactory receptor,” Block says.

“What’s also exciting is that, because olfactory receptors are transmembrane G protein-coupled receptors (GPCRs) of the same type as receptors for drugs, our discovery suggests a possibility that some drug-receptor responses may also be enhanced in the presence of copper or other metal ions.”

The senior authors on the paper were Matsunami and Shaozhong Zhuang, formerly of Duke, now of the University of Albany. Other authors include researchers at University of Albany, University of Pennsylvania School of Medicine, and Ruijin Hospital in China.

This research is supported by National Natural Science Foundation of China, the Shanghai Pujiang Program, the Shanghai Municipal Education Commission, and the Shanghai Education Development Foundation.

The U.S. National Institutes of Health (NIH), National Basic Research Program of China, U.S. National Science Foundation, and NIH/National Institute on Deafness and Other Communication Disorders also funded the work.

More news from Duke University: