Scientists discovered that SAM plays a critical role in the production of methylmercury, a highly toxic compound that contaminates seafood. Their findings could aid efforts to reduce methylmercury’s environmental impact.
Mercury is highly toxic, but it becomes particularly dangerous when converted into methylmercury—a form so harmful that even a few billionths of a gram can cause severe and lasting neurological damage to a developing fetus. Unfortunately, methylmercury frequently enters our bodies through seafood, and once it contaminates our food and environment, there is no easy way to eliminate it.
Now, leveraging high-energy X-rays at the Stanford Synchrotron Radiation Lightsource (SSRL) at the U.S. Department of Energy’s SLAC National Accelerator Laboratory, researchers have identified an unexpected major player in methylmercury poisoning – a molecule called S-adenosyl-L-methionine (SAM).
The results, published in the Proceedings of the National Academy of Sciences, could help researchers figure out new ways to address methylmercury poisoning.
“Nobody knew how mercury is methylated biologically,” said Riti Sarangi, a senior scientist in SSRL’s Structural Molecular Biology program and co-author on the paper. “We need to understand that fundamental process before we can develop an effective methylmercury remediation strategy. This study is a step toward that.”
Challenges in Studying the Elusive HgcAB Protein
At issue in the new paper is a narrow but essential mystery concerning how methylmercury is produced. Scientists knew that most of the mercury we consume starts out as industrial emissions that make their way into bodies of water, where microbes convert it into methylmercury. That form concentrates in fish – and ultimately us – as it moves up the food web.
Still, researchers weren’t sure how microorganisms make methylmercury. A key confounding factor, Sarangi said, is that the protein system that converts mercury to methylmercury, called HgcAB, is present only in very small amounts in microbes, making it extremely difficult to gather and purify enough to study. It’s also extremely finicky: The slightest exposure to oxygen and light deactivates HgcAB.
In an effort spanning 10 years and collaborations across national laboratories and universities, University of Michigan professor Steve Ragsdale, his graduate student Katherine Rush, now an assistant professor at Auburn University, and postdoctoral associate Kaiyuan Zheng developed a new protocol to yield enough stable HgcAB to finally investigate how it transforms mercury into methylmercury.
“We’ve worked with a lot of very difficult proteins, but this one had everything you would not want to have in a protein if you wanted to purify it. It was very complicated,” Ragsdale said.
Once the team purified enough HgcAB, they transported the samples – cooled by liquid nitrogen and shielded from light – to SSRL for X-ray absorption spectroscopy measurements. There, SSRL associate scientist Macon Abernathy used a method called extended X-ray absorption fine structure spectroscopy to study HgcAB.
“SSRL’s X-ray spectroscopy facilities are especially equipped to study biological samples and have powerful detector systems that can resolve the extremely weak signals of ultra dilute protein samples like these,” Sarangi said.
A Surprising Role for SAM in Methylmercury Formation
While previous studies hypothesized that the methyl group in question came from methyltetrahydrofolate, a common methyl donor in cellular reactions, the new study finds that it was donated by SAM instead. The researchers said that the results, which narrow in on the main actors in the production of methylmercury, could aid in the development of environmental remediation strategies.
“No one has tried it yet, but perhaps analogs of SAM could be developed that could address methylmercury in the environment,” Ragsdale said.
Reference: “S-adenosyl-L-methionine is the unexpected methyl donor for the methylation of mercury by the membrane-associated HgcAB complex” by Kaiyuan Zheng, Katherine W. Rush, Swapneeta S. Date, Alexander Johs, Jerry M. Parks, Angela S. Fleischhacker, Macon J. Abernathy, Ritimukta Sarangi and Stephen W. Ragsdale, 15 November 2024, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2408086121
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2 Comments
“Unfortunately, methylmercury frequently enters our bodies through seafood, and once it contaminates our food and environment, there is no easy way to eliminate it.”
Try cooking the food! Methylmercury is volatile, having a boiling point the same as water. When I was involved in some research on mercury contamination of surface waters, the commercial lab I was using advised me that if I was going to provide them with any fish, and I couldn’t get it to them within 24-hours, to freeze it.
As far as I know, there have not been any well-documented cases of methylmercury poisoning in the USA because we are not in the habit of eating raw freshwater fish; we even usually cook marine fish, unless one is an aficionado of Japanese sashimi, which also can contain worms. The government standards are very conservative because the mercury content is based on the analysis of raw fish, not cooked fish.
There are two well-documented deaths from ethylmercury, a father and son, who fed their pig seed-corn coated with the fungacide, ethylmercury. The pig died, and they ate the pig. There are a couple of lessons that should be obvious here.
Beware piggeries; a US Army cook visited a piggery at a US Army camp and caught Spanish flu from a pig. It should be called Kansas flu’ , surely? And my grandfather buried plenty of flu-raddled dead British soldiers, so I have been told, on a troopship coming back from India. Alas that there were no mRNA vaccines being produced at the time. 20-50 million dead.