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Production of the TMAO precursor TMA results from gut microbial metabolism. (a) Choline metabolism by gut microbes produce trimethylamine that can be oxidized by the host liver enzyme FMO3 or demethylated by human-associated archaea for methanogenesis. (b) Mechanism for TMA demethylation by archaeal pyrrolysine (Pyl)-containing, coronoid-dependent methyltransferases.
