Mouillé B, Morel E, Robert V, Guihot-Joubrel G, Blachier F
Laboratoire de Nutrition et Sécurité Alimentaire, Institut National de la Recherche Agronomique, F-78352, Jouy-en-Josas, France.
Biochim Biophys Acta. 1999 May 24;1427(3):401-7. doi: 10.1016/s0304-4165(99)00045-8.
Ammonia is present at high concentration in the colon lumen and is considered a colon cancer suspect. Furthermore, ammonia usually eliminated by the liver in the ornithine cycle is considered highly toxic to cerebral function when present in excess in the blood plasma. Therefore, the metabolic pathways involved in ammonia metabolism in colonocytes were studied in the present study. Rat colonocytes were found equipped with low carbamoylphosphate synthase I activity, high ornithine carbamoyltransferase and arginase activities and low argininosuccinate synthase activity. High (10 and 50 mmol/l) NH4Cl concentrations but not low concentrations (1 and 5 mmol/l) were found able to increase respectively 3- and 10-fold the conversion of radioactive L-arginine to L-citrulline. In contrast, very low capacity for L-citrulline conversion to L-arginine is found in colonocytes. It is concluded that an incomplete ornithine cycle is operative in colonocytes which results in ammonia stimulated L-citrulline production. The contribution of this metabolic pathway in relation to ammonia detoxication by colonocytes is discussed.
氨在结肠腔中以高浓度存在,被认为是结肠癌的可疑因素。此外,通常由肝脏通过鸟氨酸循环消除的氨,当血浆中过量存在时,被认为对脑功能具有高度毒性。因此,本研究对结肠细胞中氨代谢所涉及的代谢途径进行了研究。研究发现大鼠结肠细胞具有低氨甲酰磷酸合成酶I活性、高鸟氨酸氨甲酰转移酶和精氨酸酶活性以及低精氨琥珀酸合成酶活性。发现高浓度(10和50 mmol/L)的NH4Cl能够分别使放射性L-精氨酸向L-瓜氨酸的转化增加3倍和10倍,而低浓度(1和5 mmol/L)则不能。相反,结肠细胞中L-瓜氨酸向L-精氨酸的转化能力非常低。结论是,结肠细胞中存在一个不完全的鸟氨酸循环,该循环导致氨刺激L-瓜氨酸的产生。本文讨论了该代谢途径在结肠细胞氨解毒中的作用。