Takemura K, Nagase S, Aoyagi K, Gotoh M, Koyama A, Narita M
Department of Internal Medicine, Kamitsuga General Hospital, Tochigi, Japan.
Nephron. 1994;67(3):334-9. doi: 10.1159/000187989.
Plasma levels of guanidine (G) are reported to be increased in uremic patients and are synthesized from various guanidino compounds via a chemical reaction involving the hydroxyl radical in vitro. To identify both the metabolic precursor and the synthesizing organ of G, we investigated the concentrations of G in various organs of rats administered several guanidino compounds and we attempted to synthesize G biologically using isolated rat hepatocytes or perfused rat liver. In addition, we investigated the effect of the peroxidative state on the G synthesis in isolated hepatocytes using various reagents which alter this condition. Results show that the concentration of G increased in the kidney, liver and muscle following the administration of L-canavanine. In addition, G increased in the kidney at 90 min after the administration of guanidinoacetic acid (GAA). Moreover, G is synthesized from L-canavanine in isolated rat hepatocytes and perfused rat liver, and G synthesis in hepatocytes is partially inhibited by the addition of superoxide dismutase, catalase, glutathione or ethylenediaminetetraacetic acid. These results suggest that L-canavanine is possibly a biological precursor and GAA is an endogenous precursor of G. Furthermore, it is suggested that these reactions are closely related to the peroxidative state.
据报道，尿毒症患者血浆中胍（G）水平升高，且在体外可通过涉及羟基自由基的化学反应从各种胍基化合物合成。为了确定G的代谢前体和合成器官，我们研究了给予几种胍基化合物的大鼠各器官中G的浓度，并尝试使用分离的大鼠肝细胞或灌注的大鼠肝脏进行G的生物合成。此外，我们使用改变这种状态的各种试剂研究了过氧化状态对分离肝细胞中G合成的影响。结果表明，给予L-刀豆氨酸后，肾脏、肝脏和肌肉中G的浓度增加。此外，给予胍基乙酸（GAA）后90分钟，肾脏中G增加。而且，在分离的大鼠肝细胞和灌注的大鼠肝脏中，G可由L-刀豆氨酸合成，并且添加超氧化物歧化酶、过氧化氢酶、谷胱甘肽或乙二胺四乙酸可部分抑制肝细胞中的G合成。这些结果表明，L-刀豆氨酸可能是G的生物前体，GAA是G的内源性前体。此外，提示这些反应与过氧化状态密切相关。
