Study identifies pathway linking two functions of TMAO demethylase
A study links a newly identified internal tunnel to two connected functions of trimethylamine N-oxide demethylase.
AI illustrationA newly identified pathway links two functions of trimethylamine N-oxide demethylase, according to a report by Gurunath Ramanathan in eLife. The study offers a mechanistic explanation for the enzyme’s role in metabolic efficiency and detoxification.
The enzyme breaks down trimethylamine N-oxide into dimethylamine and formaldehyde. What happened to the formaldehyde had remained unclear.
The researchers found that formaldehyde travels from the catalytic core through an internal tunnel to a tetrahydrofolate-binding site, where it forms methylene-THF. This connects TMAO demethylation with one-carbon transfer within the same enzyme.
The findings draw on cryo-EM structures in apo, substrate-bound and product-bound states, together with biochemical and molecular dynamics analyses.