Endogenous formation of dimethylamine

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Abstract
An understanding of the biosynthesis and metabolism of dimethylamine (DMA) is important because it is a precursor of dimethylnitrosamine (nitroso-DMA). DMA is the major short-chain aliphatic amine in human and rat urine. DMA is formed from trimethylamine (TMA), which, in turn, is a breakdown product of dietary choline. Enzymes within gut bacteria catalyse both of these reacitons; it is not known whether mammalian cells can form DMA. To determine the relative importance of dietary choline, bacteria and other mechanisms for the formation of DMA, we measured DMA excretion in the urine of rats fed on a diet devoid of choline, and in urine of rats with no bacterial colonization of the intestines. We also describe an improved gas-chromatographic method for the measurement of methylamines in biological fluids. In control rats there were significant amounts of DMA within several biological fluids [urine, 54.2 .+-. 3.0 .mu.mol/kg body wt. per 24 h (556.2 .+-. 37.5 nmol/ml); blood, 18.8 .+-. 1.9 nmol/ml; gastric juice, 33.5 .+-. 10.5 nmol/ml; means .+-. S.E.M.]. Animals eating a diet containing no choline excreted as much MMA and DMA as did choline-supplemented rats (25-35 .mu.mol/kg per 24 h), and they excreted slightly less TMA (2 versus 2.5 .mu.mol/kg per 24 h). Rats with no gut bacteria excreted the same amount of DMA in their urine as did the control animals (45-55 .mu.mol/kg per 24 h). They excreted much less MMA (16.3 .+-. 1.5 versus 40.3 .+-. 2.6 .mu.mol/kg per 24 h; mean .+-. S.E.M.; P < 0.01), TMA (0.7 .+-. 0.2 versus 2.5 .+-. 0.5 .mu.mol/kg per 24 h; mean .+-. S.E.M.; P < 0.01) and piperidine (2.0 .+-. 0.3 versus 6.3 .+-. 0.6 .mu.mol/kg per 24 h; mean .+-. S.E.M.; P < 0.01) in their urine. From our studies we conclude that DMA is present in significant amounts within gastric fluid, an environment that is ideal for nitrosamine formation (under acidic conditions, nitroso-DMA is chemically formed by the reaction of nitrite with DMA). Results also indicate that dietary choline was not the sole precursor for DMA formation and that gut bacteria are not essential for the formation of DMA. Hence in mammals there must be endogenous pathways that are capable of forming DMA; however, these endogenous mechanisms remain unidentified.