Fish-odor enzyme advances understanding of toxic reactions

People with a rare enzyme mutation that makes their bodies smell like rotten fish find it devastating. Among those afflicted, suicide rates are high. But can those same enzymes yield desirable effects as well?

Researchers at the School of Veterinary Medicine believe it’s possible, so they are studying these enzymes, known as flavin-containing monoxygenases or FMOs.

FMOs cause fish malodor syndrome when they fail to metabolize a dietary constituent (trimethylamine). Adnan Elfarra and Mark Brownfield, both faculty in the veterinary school’s Department of Comparative Biosciences, hope that by learning how the enzymes interact with a variety of chemicals in the body, they’ll get a better sense of how chemicals can cause disease or toxicity, as well as how they may get detoxified. Their work, which is sponsored by a recently renewed National Institutes of Health grant, could help discover the physiological function of this enzyme.

FMOs are found in both human and animal tissues. They interact with a wide variety of drugs, pesticides and amino acids. The researchers are trying to determine whether these interactions can affect how the body handles certain chemicals, and, if so, whether toxicities occur as a result. The answers they find could lead to better designs of drugs and chemicals to avoid problems, help identify populations at high risk, or lead to development of prevention or intervention methods.

“Several chemical reactions can occur in our body,” Elfarra says. “Some are desirable and some are undesirable. The balance between the two determines the difference between a therapeutic and toxic response.”

Ultimately, the researchers hope to assess the risks associated with human and animal exposure to certain drugs, chemical products and environmental pollutants.

Fish-odor syndrome also occurs in a breed of dairy cattle in Sweden, where it can impact milk supplies.