INTESTINAL CARBAMOYL-PHOSPHATE SYNTHASE-I IN HUMAN AND RAT - EXPRESSION DURING DEVELOPMENT SHOWS SPECIES-DIFFERENCES AND MOSAIC EXPRESSION IN DUODENUM OF BOTH SPECIES

The clinical importance of carbamoyl phosphate synthase I (CPSI) relat es to its capacity to metabolize ammonia, because CPSI deficiencies ca use lethal serum ammonia levels. Although some metabolic parameters co ncerning liver and intestinal CPSI have been reported, the extent to w hich enterocytes contribute to ammonia conversion remains unclear with out a detailed description of its developmental and spatial expression patterns. Therefore, we determined the patterns of enterocytic CPSI m RNA and protein expression in human and rat intestine during embryonic and postnatal development, using in situ hybridization and immunohist ochemistry. CPSI protein appeared during human embryogenesis in liver at 31-35 e.d. (embryonic days) before intestine (59 e.d.), whereas in rat CPSI detection in intestine (at 16 e.d.) preceded liver (20 e.d.). During all stages of development there was a good correlation between the expression of CPSI protein and mRNA in the intestinal epithelium. Strikingly, duodenal enterocytes in both species exhibited mosaic CPS I protein expression despite uniform CPSI mRNA expression in the epith elium and the presence of functional mitochondria in all epithelial ce lls. Unlike rat, CPSI in human embryos was expressed in liver before i ntestine. Although CPSI was primarily regulated at the transcriptional level, CPSI protein appeared mosaic in the duodenum of both species, possibly due to post-transcriptional regulation.