Metabolic capacity for l-citrulline synthesis from ammonia in rat isolated colonocytes

Abstract

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) NH 4Cl 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.