Abstract
Trimethylamine (TMA) and its N-oxide (TMAO) are ubiquitous in prokaryote and eukaryote organisms as well as in the environment, reflecting their fundamental importance in evolutionary biology, and their diverse biochemical functions. Both metabolites have multiple biological roles including cell-signaling. Much attention has focused on the significance of serum and urinary TMAO in cardiovascular disease risk, yet this is only one of the many facets of a deeper TMA-TMAO partnership that reflects the significance of these metabolites in multiple biological processes spanning animals, plants, bacteria, and fungi. We report on analytical methods for measuring TMA and TMAO and attempt to critically synthesize and map the global functions of TMA and TMAO in a systems biology framework.
Highlights
Trimethylamine (TMA) and its N-oxide (TMAO) are ubiquitous in prokaryote and eukaryote organisms as well as in the environment, reflecting their fundamental importance in evolutionary biology, and their diverse biochemical functions
Because there is no age-associated difference in flavin-monooxygenase 3 (FMO3) abundance,[123] the association between age and increased excretion of TMAO and DMA more likely reflects the inefficiency of renal osmolyte systems associated with aging[122] or alternatively may reflect age-related changes in the microbiome and the consequent production of TMA
TMAO is directly dependent on the bacterial production of TMA, they have divergent biological roles
Summary
Methylamines are found in organisms spanning all five major kingdoms (Animalia, Plantae, Fungi, Protista, and Monera) and can be synthesized in shared and unique metabolic pathways in both eukaryotic and prokaryotic organisms or even abiotically (Figure 1). The ubiquitous presence of methylamines is consistent with them having fundamental roles in evolutionary biology. This Review summarizes the multiple biological functions of trimethylamine (TMA) and its oxide, trimethylamine-N-oxide (TMAO), with a focus on their role in humans and their influence on physiological and pathophysiological processes. A review by Chhibber-Goel et al provides a concise summary of some of the lesser known history of TMA research.[1] chemically related, TMA and TMAO have very different physicochemical properties and biological functions, with TMA frequently acting as a pheromone or chemical signaling agent and TMAO most often serving as a cellular protector or disruptant depending on the chemical context.
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