Zeisel S H, DaCosta K A, Fox J G
Biochem J. 1985 Dec 1;232(2):403-8. doi: 10.1042/bj2320403.
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 reactions; 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 mumol/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 mumol/kg per 24 h), and they excreted slightly less TMA (2 versus 2.5 mumol/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 mumol/kg per 24 h). They excreted much less MMA (16.3 +/- 1.5 versus 40.3 +/- 2.6 mumol/kg per 24 h; mean +/- S.E.M.; P less than 0.01), TMA (0.7 +/- 0.2 versus 2.5 +/- 0.5 mumol/kg per 24 h; mean +/- S.E.M.; P less than 0.01) and piperidine (2.0 +/- 0.3 versus 6.3 +/- 0.6 mumol/kg per 24 h; mean +/- S.E.M.; P less than 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.
了解二甲胺（DMA）的生物合成和代谢很重要，因为它是二甲基亚硝胺（亚硝基 - DMA）的前体。DMA是人和大鼠尿液中的主要短链脂肪族胺。DMA由三甲胺（TMA）形成，而TMA又是膳食胆碱的分解产物。肠道细菌中的酶催化这两个反应；目前尚不清楚哺乳动物细胞是否能形成DMA。为了确定膳食胆碱、细菌和其他形成DMA的机制的相对重要性，我们测量了喂食不含胆碱饮食的大鼠尿液以及肠道无细菌定植的大鼠尿液中的DMA排泄量。我们还描述了一种改进的气相色谱法，用于测量生物体液中的甲胺。在对照大鼠的几种生物体液中存在大量DMA[尿液，每24小时54.2±3.0μmol/kg体重（556.2±37.5nmol/ml）；血液，18.8±1.9nmol/ml；胃液，33.5±10.5nmol/ml；平均值±标准误]。食用不含胆碱饮食的动物排泄的甲基丙二酸（MMA）和DMA与补充胆碱的大鼠一样多（每24小时25 - 35μmol/kg），且它们排泄的TMA略少（每24小时2μmol/kg对2.5μmol/kg）。无肠道细菌的大鼠尿液中DMA排泄量与对照动物相同（每24小时45 - 55μmol/kg）。它们尿液中排泄的MMA、TMA和哌啶要少得多[每24小时16.3±1.5μmol/kg对40.3±2.6μmol/kg；平均值±标准误；P＜0.01；每24小时0.7±0.2μmol/kg对2.5±0.5μmol/kg；平均值±标准误；P＜0.01；每24小时2.0±0.3μmol/kg对6.3±0.6μmol/kg；平均值±标准误；P＜0.01]。从我们的研究中我们得出结论，胃液中存在大量DMA，胃液是亚硝胺形成的理想环境（在酸性条件下，亚硝基 - DMA由亚硝酸盐与DMA的反应化学形成）。结果还表明，膳食胆碱不是DMA形成的唯一前体，肠道细菌对于DMA的形成也不是必需的。因此，在哺乳动物中一定存在能够形成DMA的内源性途径；然而，这些内源性机制仍未明确。
