Biosynthesis and turnover of trimethylamine oxide in the teleost cod, Gadus morhua

Liver and kidney of the teleost cod, Gadus morhua, contained oxygen- and NADPH-dependent monooxygenase which mediated the oxidation of trimethylamine (TMA) to trimethylamine oxide (TMAO). The microsomal monooxygenase of liver was partially characterized. The rate of enzymic TMA oxidation had its maximum at pH 8.2 and at 24 degrees C. The enzyme displayed Michaelis-Menten kinetics; the apparent Km value for TMA being 11 microM. All N,N-dimethyl-n-alkylamines with up to 8 carbons in the side chain were oxidized at almost the same rate. The oxidation of TMA was stimulated by octylamine and tyramine, and its ws inhibited by the --SH reagents N-ethylmaleimide and p-chloromercurybenzoate. Lack of inhibition by carbon monoxide and stimulation by FAD indicated that the enzyme was a cytochrome P-450-independent flavoprotein. [14C]TMA injected intraperitoneally into cod was oxidized to [14C]TMAO. After its compartmentation the [14C]TMAO produced was excreted at a rate of approximately 0.5%/day in cod fed a TMAO-rich diet. It was inferred that high stability of body TMAO and a surplus amount of TMAO in their natural diet can explain the lack of endogenous TMAO synthesis encountered in many TMAO-containing marine fish.