Analysis, biology and significance of dimethylamine, trimethylamine and trimethylamine N-oxide in humans and in the marine ecosystem

Dimethylamine (DMA) and its relatives including trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widely distributed in nature including humans and the marine ecosystem. This article gives an overview of the origin, occurrence, metabolism and potential functions of dimethylamine in human life and of the DMA-TMA-TMAO axis in the marine ecosystem. In humans, a dimethylamine fraction of about 80-90 % is of endogenous origin. The remaining 10-20 % is of exogenous origin, notably of foods and especially of certain fish and seafood. Several different analytical methods are available for the quantitative determination of dimethylamine, trimethylamine and trimethylamine N-oxide in biological samples including human urine and fish. Frequently used methods include GC-FID, GC-ECD, GC-MS and more recently LC-MS/MS. A widely used GC-MS method of dimethylamine in human urine includes its extractive derivatization with pentafluorobenzoyl chloride. The dimethylamine concentration in plasma and serum is of the oder of 3 μM in healthy humans and several times higher in humans suffering from chronic kidney diseases. The dimethylamine concentration in human urine may range between 100 μM and 1500 μM, corresponding to mean creatinine-corrected excretion rates of 10 to 80 μmol dimethylamine/mmol creatinine in adults and up to 400 μmol dimethylamine/mmol creatinine in children and adolescents. GC-MS methods have contributed greatly to a better understanding of the biology of dimethylamine in health and disease. In humans, up to 90 % of urinary dimethylamine is considered a measure of its endogenous synthesis from post-translational dimethylation of arginine residues in proteins. This abundant post-translational modification leads to asymmetrically dimethylated arginine proteins, which, upon regular proteolysis, generate asymmetrical dimethylarginine (ADMA) that is finally hydrolyzed to and L-citrulline and dimethylamine, which is then readily excreted in the urine. In fishery, dimethylamine and trimethylamine are discussed as indicators of freshness due to their enhanced production of microbiomal activity. High amounts of dimethylamine are found in canned fish. Dimethylamine is considered the precursor of the cancerogenic N-nitroso-dimethylamine. Other non-volatile amines such as histamine and agmatine seem to be better suitable as fish freshness indicators. High contents of the order of several mmol trimethylamine N-oxide per kg tissue are found in fish in dependence on the habitat depth. It is assumed that trimethylamine N-oxide act as osmolytic and piezolytic agent. The significance of trimethylamine N-oxide in human health and disease is elusive.