Journal News

Stabilizing the enzyme in fish odor syndrome

Mussa Quareshy
By Mussa Quareshy
December 06, 2020

Fish odor syndrome, or trimethylaminuria, is a disease in which the liver cannot break down the smelly chemical trimethylamine, or TMA, that is produced by enzymes from bacteria residing in the gut. There is no cure for fish odor syndrome, which gives people an unpleasant fishy smell that can affect breath, sweat, urine and vaginal fluids.

FishOdor-226x600.jpg
University of Warwick
Top: protein crystals of CntA enzyme; middle: a cartoon depiction of CntA enzyme in its functional trimeric state; bottom: detailed view of carnitine bound in the active site of CntA prior to cleavage.

Our research team at the University of Warwick is working to prevent the syndrome through studying the enzyme in the gut that produces trimethylamine.

Fish odor syndrome starts when an enzyme pathway in the gut called CntA/B produces TMA. 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 degrade TMA into a non-smelly chemical form, trimethylamine oxide, or TMAO. The TMA then builds up in the body and ends up in bodily fluids.

In a recent paper, published in the Journal of Biological Chemistry, our team in Yin Chen's lab at Warwick's School of Life Sciences focused on the CntA protein of the CntA/B enzyme, to stabilize and study it.

CntA/B is a notoriously hard enzyme to study, but once it was stabilized, we were able to gain insight into how CntA perceives its L-carnitine substrate with a 3D crystal structure model, and by studying the complete electron transfer pathway, we could see how the protein is able to turn over TMA.

Now that we understand how exactly TMA is produced in the gut and that the enzyme can be inhibited, there are grounds for further research into future discovery of drugs targeting the TMA-producing enzyme in the human gut.

We have identified novel, drug-like inhibitors that can inhibit CntA function and thus TMA formation with the potential to attenuate TMA formation in the gut microbiome. This is vital not only for people who have fish odor syndrome, but also because TMA can accelerate atherosclerosis and heart disease.
 

This article was adapted from a University of Warwick press release. Read the original here.

Mussa Quareshy
Mussa Quareshy

Mussa Quareshy grew up in Malawi, then moved to the U. K. where he earned a master’s degree in pharmaceutical sciences at the University of Leicester and a Ph.D. at Warwick University, studying the plant hormone Auxin and its receptor. He is a postdoc research fellow in Yin Chen’s lab in the School of Life Sciences at Warwick where his research interests are primarily studying protein ligand interactions with an interest in drug discovery projects.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

Branon works to break barriers in science and higher education
ASBMB Annual Meeting

Branon works to break barriers in science and higher education

March 03, 2021

Tess Branon will speak on proximity-dependent biotinylation during the Molecular & Cellular Proteomics early-career researcher session at the 2021 ASBMB Annual Meeting.

Brain Injury Awareness Month 2021
Health Observance

Brain Injury Awareness Month 2021

March 01, 2021

In the U.S., about 2.8 million people sustain a traumatic brain injury annually. Learn about recent research on TBI-related dementia, dysfunctional mitochondria and other work powering the march toward better therapies.

The evolution of proteins from mysteries to medicines
Essay

The evolution of proteins from mysteries to medicines

February 27, 2021

An essay in observance of National Protein Day.

'Every experiment and every breakthrough matters'
Health Observance

'Every experiment and every breakthrough matters'

February 26, 2021

An interview with NYMC dean Marina K. Holz, who studies a rare disease that affects women of childbearing age.

Progeria: From the unknown to the first FDA-approved treatment
Health Observance

Progeria: From the unknown to the first FDA-approved treatment

February 25, 2021

Hutchinson–Gilford progeria syndrome is a rare, fatal genetic disease that causes premature aging.

Raising awareness and funding for Pompe disease
Health Observance

Raising awareness and funding for Pompe disease

February 25, 2021

Father-turned-advocate has founded multiple organizations to support families and search for better therapies for people with rare lysosomal storage disorder.