Conversion of arginine to proline in murine schistosomiasis

Abstract

Free proline, an important amino acid for collagen synthesis, is increased in fibrotic livers of mice with schistosomiasis. Formation of collagen by fibrotic liver slices in vitro has been shown to depend on the concentration of proline in incubation medium. To determine the likely source of free proline in liver, we compared conversion of arginine and glutamic acid to proline by normal livers and by fibrotic livers obtained 9 weeks after infection of mice with 50 Schistosoma mansoni cercariae. Pools of most free amino acids, including glutamic acid and proline, were increased in fibrotic liver. Liver slices were incubated with either [14C]arginine or [14C]glutamic acid in the presence of 0.1 mM concentration of both unlabeled amino acids in the medium. After a 6-hr incubation, arginine-derived free proline was 1.82 ± 0.44 μmoles per g of liver protein in fibrotic liver and 0.93 ± 0.20 μmoles per g of liver protein in normal liver. Fibrotic livers utilized arginine-derived proline for collagen synthesis, forming 6.3 ± 1.7 nmoles of protein-bound hydroxyproline per g of liver protein in 6 hr. In contrast, however, conversion of glutamic acid to proline was not detected under the experimental conditions employed. Glutamine was not converted to proline in similar liver slice experiments. Conversion of arginine in vivo to proline utilized for liver collagen synthesis was confirmed in mice with schistosomiasis after intraperitoneal injection of [14C]arginine. Conversion of [14C]glutamine to liver proline in vivo appeared to be minimal. These studies suggest that arginine may be a major precursor of the increased free proline pool in murine schistosomiasis, and that conversion of arginine to proline may be important for the over-all pathway of liver collagen formation.