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Fish odor syndrome (trimethylaminuria) is a debilitating disease, in which the liver cannot break down the stinky chemical trimethylamine produced by the enzymes of bacteria residing in the gut, leaving people with a fish-like odor. Researchers at the University of Warwick are leading the way in preventing the syndrome after a breakthrough in studying the enzyme in the gut that produces trimethylamine.
There is currently no cure for fish odor syndrome, a condition that causes an unpleasant fishy smell that can affect your breath, sweat, pee and vaginal fluids.
The cause of fish odor syndrome is when an enzymatic pathway in the gut called CntA / B produces TMA, this happens when the enzyme breaks down a TMA precursor called L-Carnitine which is found in dairy, fish and meat. . If an individual lacks a functional liver enzyme called FMO3, they cannot break down TMA to a non-smelly chemical form, TMAO (trimethylamine oxide). The TMA then builds up in the body and ends up in the body fluids.
In the paper, “Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition and inter-subunit electron transfer” published in Journal of Biological Chemistry, researchers from the University of Warwick School of Life Sciences specifically focused on the CntA protein of the CntA / B enzyme, to stabilize and study it.
CntA / B is a notoriously difficult enzyme to study, but once stabilized the research group of Prof. Yin Chen was able to obtain information on how CntA perceives its L-carnitine substrate, with a 3D crystal structure model. and by studying the complete electron transfer path they could see how the protein is able to transform TMA.
Now that it is understood how exactly TMA is produced in the gut and that the enzyme can be inhibited, there are grounds for further research on future drug discovery that target the TMA-producing enzyme in the human gut.
Lead researcher, Dr Mussa Quareshy, of the University of Warwick School of Life Sciences comments, ‘We have identified novel drug-like inhibitors that can inhibit CntA function and thus TMA formation with the potential to attenuate TMA formation. gut microbiome. This is vital not only for people who have fish odor syndrome but also because TMA can accelerate atherosclerosis and heart disease, so the urgency of being targeted by drugs is quite significant “.
The researchers acknowledge the generous funding supported by a Leverhulme Fiduciary Scholarship (RPG-2016-307).
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