Studies on the metabolism of dimethylarginines in rats

N^G，N^G-和N^G，N‘^G-二甲基精氨酸(DMA和DM’A)存在于翻译后甲基化的天然蛋白质中。一些研究人员建议，在没有详细代谢研究的情况下，将这些氨基酸作为蛋白质周转的指标，类似于N^&lt；&lt；tau&gt；&gt；甲基组氨酸。然而，我们的实验证明，这些二甲基精氨酸在大鼠体内确实有代谢。在独特的氨基转移酶的催化下，DMA和DM‘A都可以转化为N^&lt；α&gt；-乙酰基偶联物和酮酸。此外，还发现-酮酸的氧化脱羧基产物也是代谢产物。此外，还发现DMA被分解为L-瓜氨酸和其他与尿素循环有关的氨基酸。我们发现了一种新的负责DMA代谢过程的酶，它将DMA直接转化为L-瓜氨酸的过程与DMA甲基化胍基部分的二甲胺水解性释放相结合。这些酶是从大鼠肾脏中提纯出来的，并被完全鉴定为新的酶。这些发现表明，将上述二甲基精氨酸作为体内蛋白质分解的指标的尝试至少在大鼠中是不可行的。

N^G,N^G - and N^G,N'^G -Dimethylarginine (DMA and DM'A) occur in natural proteins methylated post-translationally. Some investigators proposed to use these amino acids as an index of protein turnover in a similar manner to N^<<tau>> methylhistidine, without detailed metabolic studies. By our experiments, however, it was proved that these dimethylarginines were definitely metabolized in rats. Both DMA and DM'A were converted to N^<alpha> -acetyl conjugates and to -keto acids by unique aminotransferase catalyzing the transamination between DMA (DM'A) and pyruvate. In addition, the oxidatively decarboxylated products of the -keto acids were also found as the metabolites. Moreover, it was shown that DMA was catabolized to L-citrulline and other amino acids metabolically related to urea cycle. We found a novel enzyme responsible for the metabolic process of DMA, which catalizes the direct conversion of DMA to L-citrulline with hydrolytic liberation of dimethylamine from the methylated guanidino moiety of DMA. These enzymes were purified from rat kidney and were fully characterized as new enzymes.These findings shows that the attempt to use the above-mentioned dimethyl-arginines as an index of in vivo protein breakdown is inadeqate at least in rats.