- 'Fish odour syndrome' occurs when the body can’t process a foul-smelling chemical called trimethylamine
- While there’s no cure, scientists have pinpointed the enzyme that produces this chemical in the gut
- This could pave the way for the development of ways to inhibit trimethylamine at its source
You are what you eat – and it’s a well-known fact that what we feed our gut microbes affects our general health.
These microscopic workers, however, don’t always produce the best-smelling results. Certain nutrients can be transformed by the gut microbiota into small amounts of methylated amines like trimethylamine (TMA).
But why should we care about TMA? The answer is that it exudes a bad smell called trimethylaminuria – or 'fish odour syndrome'.
The problem with trimethylamine
Normally the amine is broken down by the liver into a chemical that doesn’t smell, but in rare cases it doesn’t happen due to a mutated gene. It eventually builds up in the body, causing a pungent fishy smell, which can lead to potential social and psychological problems for the afflicted. It can radiate from your breath, sweat, urine and even vaginal fluids.
Some foods that contribute to TMA production in the gut include eggs, liver, legumes and fish.
In order to combat this debilitating syndrome, one needs to know which enzymes in the gut produce TMAs.
Reconstructing an enzyme protein
While identifying the culprit has proven to be tricky, researchers from the University of Warwick found the enzyme that produces TMA, and successfully managed to inhibit its production. They published their findings in the Journal of Biological Chemistry.
The enzyme is called CntA/B. It was, however, difficult to analyse until the researchers succeeded in making it more stable through crystallisation.
“Different expression strategies or the choice of buffers and additives may have contributed to the apparent differences in enzyme activities among studies of CntA protein,” according to the report.
“Due to sensitivity to oxygen, considerable effort was made in our work in order to obtain CntA crystals.”
How crystals are formed
These crystals were obtained by placing drops of CntA onto a microscopic slide at 22 degrees Celsius, where it took two days for crystals to form. After a few more steps, the scientists flash-froze the crystals with liquid nitrogen.
From these crystals, they created a 3D digital structure to simulate how CntA protein produces TMA.
Future drug development
“The identification of the key microbial enzymes, including the choline-TMA lyase and CntA provides promising new drug targets for attenuating TMA release from gut microbial metabolism of TMA-precursors,” added the researchers.
While it’s not yet a cure, it’s the first step towards developing a treatment for those affected by TMA.
“This is vital not only for people who have fish odour syndrome, but also because TMA can accelerate atherosclerosis and heart disease, therefore its urgency to be targeted by drugs is rather significant,” said lead researcher Dr Mussa Quareshy.