Development of the Ornithine Cycle in Rat Liver: Zonation of A Metabolic Pathway

Ammonia-fixation in mammalian livers is, via the ornithine cycle and glutamine synthetase, strictly compartmentalized, occurring in a wide upstream periportal compartment and in the very last downstream pericentral hepatocytes, respectively. This conclusion is based on the well-known distribution patterns of carbamoyl phosphate synthetase I (CPS) and glutamine synthetase in the developing and adult liver. To determine to what extent the expression patterns of the ornithine cycle enzymes are coordinated with that of CPS, we investigated the patterns of expression of the individual messenger RNAs (mRNAs) of the ornithine cycle pathway in developing and adult rat liver. Our results show that, within the liver, all mRNAs of the ornithine cycle pathway are zonated. The patterns of expression of the different mRNAs match almost perfectly, with variations only in the steepness of the gradients of the mRNAs, suggesting that, in the rat, common regulatory factors are involved in the establishment of the zonation pattern.