Efficacy of FMO3 enzyme

The FMO3 enzyme is structured as a protein molecule, composed of a linear sequence of amino acids folded into a specific three-dimensional shape. This shape is crucial for the enzyme's function, as it determines how the enzyme interacts with its substrates and cofactors.

The primary elements that constitute the FMO3 enzyme include :

  1. Amino acids

    2. These are the building blocks of proteins and are arranged in a specific sequence according to the genetic information encoded by the FMO3 gene.

  2. Cofactors

    3. The FMO3 enzyme requires non-protein molecules called cofactors to facilitate its catalytic activity. The primary cofactor for FMO3 is flavin adenine dinucleotide (FAD), which acts as a coenzyme by accepting and donating electrons during oxidation-reduction reactions.

  3. Active site

    4. This is a region of the enzyme where the substrate molecule binds and undergoes a chemical reaction. In the case of FMO3, the active site accommodates trimethylamine (TMA) and other substrates for oxidation.

  4. Catalytic residues

    5. These are specific amino acids within the active site that directly participate in the catalytic reaction, facilitating the conversion of substrates into products. In FMO3, catalytic residues help mediate the transfer of oxygen atoms during the oxidation of TMA to trimethylamine N-oxide (TMAO).


Various parameters are employed to evaluate the catalytic activity of flavin-containing monooxygenase 3 (FMO3) and discern impairments in enzyme function. One crucial parameter is the rate of reaction, which quantifies the velocity at which FMO3 catalyzes the oxidation of substrates, such as trimethylamine (TMA) or endogenous compounds.

A higher reaction rate typically signifies efficient enzyme activity, while a diminished rate may indicate impaired FMO3 function. Additionally, the percentage or ratio of substrate concentrations to metabolite formation serves as an essential indicator of FMO3 activity.

In the context of Trimethylaminuria (TMAU), alterations in the ratio of trimethylamine N-oxide (TMAO) to trimethylamine (TMA) concentrations serve as indicators of FMO3-mediated TMA oxidation efficiency, pivotal in TMAU symptomatology. Kinetic studies elucidate the enzyme's substrate affinity and catalytic efficiency through parameters such as the Michaelis-Menten constant (Km) and catalytic rate constant (Kcat). Specifically, the Kcat/Km ratio, when reduced to less than 50% of wild-type levels, typifies severe TMAU, reflecting a substantial decrease in FMO3's catalytic prowess. Conversely, ratios between 50% and 90% signify milder TMAU presentations, denoting a partial loss of enzymatic activity. These quantitative assessments offer nuanced insights into the pathophysiological spectrum of TMAU and guide tailored therapeutic interventions.

Last updated : March 2024