HEPATIC ZONATION OF THE CATABOLISM OF ARGININE AND ORNITHINE IN THE PERFUSED-RAT-LIVER

The metabolism of C-14-labelled arginine and ornithine was studied in the isolated, nonrecirculating, perfused rat liver. The catabolism of these amino acids required ornithine aminotransferase since treatment of rats with gabaculine, an inhibitor of this enzyme, decreased substa ntially the production of (CO2)-C-14 from the C-14-labelled amino acid s. In the liver, ornithine aminotransferase is restricted to a small p opulation of hepatocytes proximal to the terminal hepatic vein [Kuo, F . C., Hwu, W. L., Valle, D. and Darnell Jr., J. E. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 9468-9472], i.e. the perivenous subpopulation of hepatocytes. Catabolism of arginine requires arginase to convert argi nine to ornithine which can then be catabolized through ornithine amin otransferase. The presence of arginase activity in the perivenous hepa tocytes was demonstrated by experiments in which livers were perfused with [C-14]arginine in both antegrade and retrograde directions. Ident ical rates of (CO2)-C-14 production were obtained in these experiments , a result which could only occur if the process of arginine catabolis m through ornithine aminotransferase can be carried out in its entiret y in the perivenous cells.